BACKGROUND Diabetic ketoacidosis(DKA)is a serious complication of type 1 diabetes mellitus(T1DM).Very rarely does DKA lead to cerebral edema,and it is even rarer for it to result in cerebral infarction.Bilateral inter...BACKGROUND Diabetic ketoacidosis(DKA)is a serious complication of type 1 diabetes mellitus(T1DM).Very rarely does DKA lead to cerebral edema,and it is even rarer for it to result in cerebral infarction.Bilateral internal carotid artery occlusion(BICAO)is also rare and can cause fatal stroke.Moreover,case reports about acute cerebral infarction throughout both internal carotid arteries with simultaneous BICAO are very scarce.In this study,we present a patient with BICAO,T1DM,hypertension,and hyperlipidemia,who had a catastrophic bilateral cerebral infarction after a DKA episode.We briefly introduce BICAO and the mechanisms by which DKA results in cerebral infarction.CASE SUMMARY A 41-year-old woman presented with ischemic stroke that took place 3 mo prior over the left corona radiata,bilateral frontal lobe,and parietal lobe with right hemiplegia and Broca’s aphasia.She had a history of hypertension for 5 years,hyperlipidemia for 4 years,hyperthyroidism for 3 years,and T1DM for 31 years.The first brain magnetic resonance imaging not only revealed the aforementioned ischemic lesions but also bilateral internal carotid artery occlusion.She was admitted to our ward for rehabilitation due to prior stroke sequalae.DKA took place on hospital day 2.On hospital day 6,she had a new massive infarction over the bilateral anterior cerebral artery and middle cerebral artery territory.After weeks of aggressive treatment,she remained in a coma and on mechanical ventilation due to respiratory failure.After discussion with her family,compassionate extubation was performed on hospital day 29 and she died.CONCLUSION DKA can lead to cerebral infarction due to several mechanisms.In people with existing BICAO and several stroke risk factors such as hypertension, T1DM,hyperlipidemia, DKA has the potential to cause more serious ischemic strokes.展开更多
The use of operating microscopes is limited by the focal length.Surgeons using these instruments cannot simultaneously view and access the surgical field and must choose one or the other.The longer focal length (more...The use of operating microscopes is limited by the focal length.Surgeons using these instruments cannot simultaneously view and access the surgical field and must choose one or the other.The longer focal length (more than 1 000 mm) of an operating telescope permits a position away from the operating field,above the surgeon and out of the field of view.This gives the telescope an advantage over an operating microscope.We developed a telescopic system using screen-imaging guidance and a modified portable video macroscope constructed from a Computar MLH-10 × macro lens,a DFK-21AU04 USB CCD Camera and a Dell laptop computer as monitor screen.This system was used to establish a middle cerebral artery occlusion model in rats.Results showed that magnification of the modified portable video macroscope was appropriate (5-20 ×) even though the Computar MLH-10 × macro lens was placed 800 mm away from the operating field rather than at the specified working distance of 152.4 mm with a zoom of 1-40 ×.The screen-imaging telescopic technique was clear,life-like,stereoscopic and matched the actual operation.Screen-imaging guidance led to an accurate,smooth,minimally invasive and comparatively easy surgical procedure.Success rate of the model establishment evaluated by neurological function using the modified neurological score system was 74.07%.There was no significant difference in model establishment time,sensorimotor deficit and infarct volume percentage.Our findings indicate that the telescopic lens is effective in the screen surgical operation mode referred to as "long distance observation and short distance operation" and that screen-imaging guidance using an modified portable video macroscope can be utilized for the establishment of a middle cerebral artery occlusion model and micro-neurosurgery.展开更多
Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography an...Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffu- sion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially in- creased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion co- efficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at remote regions (cerebellum) varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis.展开更多
The present study aimed to verify the practicability of performing screen-based surgical operations under the guidance of a real-time viewing and recording system (RTVRS) using a portable medium-soft electronic endo...The present study aimed to verify the practicability of performing screen-based surgical operations under the guidance of a real-time viewing and recording system (RTVRS) using a portable medium-soft electronic endoscope (pmsEE). The middle cerebral artery in rats was occluded under screen-imaging guidance using a pmsEE RTVRS to reproduce an animal model of human cerebral infarction. The screen imaging of the pmsEE RTVRS was clear, life-like, stereoscopic and synchronous with the actual operation. Screen-imaging guidance led to an accurate, smooth, minimally invasive and comparatively easy surgical procedure. The surgical success rate, time of model establishment, neurological function scores, and infarct volume were similar to those using an operating microscope. These results indicate that the self-designed pmsEE RTVRS could be utilized for portable endoscopic screen-based surgical operations.展开更多
In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes (T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]) follow...In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes (T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]) following cerebral infarction. The pathological changes were divided into three phases: early cerebral infarction, middle cerebral infarction, and late cerebral infarction. In the early cerebral infarction phase (less than 2 hours post-infarction), there was evidence of intracellular edema, which improved after reperfusion. This improvement was defined as the ischemic penumbra. In this phase, a high DWI signal and a low apparent diffusion coefficient were observed in the right basal ganglia region. By contrast, there were no abnormal T2WI and T2FLAIR signals. For the middle cerebral infarction phase (2-4 hours post-infarction), a mixed edema was observed. After reperfusion, there was a mild improvement in cell edema, while the angioedema became more serious. A high DWI signal and a low apparent diffusion coefficient signal were observed, and some rats showed high T2WI and T2FLAIR signals. For the late cerebral infarction phase (4-6 hours post-infarction), significant angioedema was visible in the infarction site. After reperfusion, there was a significant increase in angioedema, while there was evidence of hemorrhage and necrosis. A mixed signal was observed on DWI, while a high apparent diffusion coefficient signal, a high T2WI signal, and a high T2FLAIR signal were also observed. All 86 cerebral infarction patients were subjected to T2WI, T2FLAIR, and DWI. MRI results of clinic data similar to the early infarction phase of animal experiments were found in 51 patients, for which 10 patients (10/51) had an onset time greater than 6 hours. A total of 35 patients had MRI results similar to the middle and late infarction phase of animal experiments, of which eight patients (8/35) had an onset time less than 6 hours. These data suggest that defining the "therapeutic time window" as the time 6 hours after infarction may not be suitable for all patients. Integrated application of MRI sequences including T2WI, T2FLAIR, DW-MRI, and apparent diffusion coefficient mapping should be used to examine the ischemic penumbra, which may provide valuable information for identifying the "therapeutic time window".展开更多
BACKGROUND: Previously, only single short-time low-dose hyperbaric oxygenation (HBO) protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few...BACKGROUND: Previously, only single short-time low-dose hyperbaric oxygenation (HBO) protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time (can cover all the natural pathologic progression period) high-dose HBO to treat the disease. OBJECTIVE: To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion (MCAO) in rats. DESIGN: A randomized controlled experimental study. SETTING: Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS: Seventy-four male SD rats, aged 2.5 months old, weighing ( 280 + 20) g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin (made in China). METHODS: This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention: All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups (9 hours and 18 hours) and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours l, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, l0 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation: Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES: ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS: ① Neurobehavioral outcome: After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group (P 〈 0.01). Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group (P 〈 0.01). ② Cerebral infarct volume: Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling (P 〈 0.01). In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling (P 〈 0.05). ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION: High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.展开更多
We investigated the effects of ipsilateral versus bilateral limb-training on promotion of endogenous neural stem cells in the peripheral infarct zone and the corresponding cerebral region in the unaffected hemisphere ...We investigated the effects of ipsilateral versus bilateral limb-training on promotion of endogenous neural stem cells in the peripheral infarct zone and the corresponding cerebral region in the unaffected hemisphere of rats with cerebral infarction. Middle cerebral artery occlusion was induced in Wistar rats. The rat forelimb on the unaffected side was either wrapped up with tape to force the use of the paretic forelimb in rats or not braked to allow bilateral forelimbs to participate in training. Daily training consisted of mesh drum training, balance beam training, and stick rolling training for a total of 40 minutes, once per day. Control rats received no training. At 14 days after functional training, rats receiving bilateral limb-training exhibited milder neurological impairment than that in the ipsilateral limb-training group or the control group. The number of nestin/glial fibrillary acidic protein-positive and nestin/microtubule-associated protein 2-positive cells in the peripheral infarct zone and in the corresponding cerebral region in the unaffected hemisphere was significantly higher in rats receiving bilateral limb-training than in rats receiving ipsilateral limb-training. These data suggest that bilateral limb-training can promote the proliferation and differentiation of endogenous neural stem cells in the bilateral hemispheres after cerebral infarction and accelerate the recovery of neurologic function. In addition, bilateral limb-training produces better therapeutic effects than ipsilateral limb-training.展开更多
Acute aortic dissection is a life-threatening condition requiring immediate assessment and therapy. Rarely, aortic dis-section involves carotid arteries and manifest cerebral infarction. Here, we report a case of aort...Acute aortic dissection is a life-threatening condition requiring immediate assessment and therapy. Rarely, aortic dis-section involves carotid arteries and manifest cerebral infarction. Here, we report a case of aortic dissection complicated with fatal cerebral infarction. A 83-year-old man, who suddenly suffered consciousness disturbance and right hemiparesis, was transferred to our hospital for the treatment of stroke. Magnetic resonance image revealed massive cerebral infarction in the left cerebral hemisphere as well as occlusion of the left internal carotid artery. Duplex ultrasonography demonstrated arterial dissection in the bilateral carotid arteries and the blood flow was compromised especially in the left side. Aortic dissection was confirmed by the contrast enhanced computed tomography. He was treated conservatively and died of cerebral hernia three days after the onset. In conclusion, aortic dissection may involve carotid artery and results in cerebral infarction. Ultrasound screening can aid timely diagnosis of aortic dissection and further management.展开更多
In multiple trauma, blunt carotid artery injuries (BCAIs) have occasionally been reported. However, bilateral blunt carotid artery occlusions (Grade 4 BCAIs) associated with multiple trauma are rare, and delays in dia...In multiple trauma, blunt carotid artery injuries (BCAIs) have occasionally been reported. However, bilateral blunt carotid artery occlusions (Grade 4 BCAIs) associated with multiple trauma are rare, and delays in diagnosis and treatment result in a lethal outcome. Here, we report our experience with bilateral carotid artery occlusions. A 76-year-old female suffered multiple traumas in a motor vehicle accident. On arrival at our hospital, she presented in a coma, with left mydriasis and unreactive pupils. Computed tomography (CT) showed bifrontal intracranial epidural hematoma and fractures of the facial bone and anterior skull base, and osteoplastic craniotomy was urgently undertaken for the epidural hematoma. However, the comatose state and unreactive pupils persisted during the post-operative course. Serial head CT findings showed progressive bilateral ischemic changes, and radiological examinations revealed bilateral internal carotid artery occlusions. We speculated that bilateral Grade 4 BCAIs had induced progressive cerebral infarctions. The patient partially responded to anticoagulation therapy with heparin infusion, but died of multiple organ failure on day 15. When bilateral progressive ischemic changes are observed in a patient with severe traumatic brain injury, bilateral Grade 4 BCAIs should be considered in the differential diagnosis. CT angiography as part of whole-body CT at admission may be effective for preventing delays in diagnosis and treatment of bilateral Grade 4 BCAIs.展开更多
The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with...The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with fructose 1,6 diphosphate (FDP) 200 and 350 mg·kg 1 ip immediately after MCAO, respectively, significantly reduced the infarction area and volume in a dose dependent manner. MK801 and FDP also displayed a protective effect on brain ischemia. A combination of Tet and FDP administered immediately after MCAO, produced a more potent protective effect than those treated with Tet or FDP alone. When Tet or FDP was administered 1 h and 2 h after MCAO, respectively, they could still significantly reduce the infarction area and volume of brain tissue. But, there was no significant protective effect when these two compounds were given 3 h after MCAO.展开更多
A rat model of middle cerebral artery permanent occlusion was established using the modified Longa method. Successfully established model animals were treated by blood-letting puncture at twelve Jing-Well points of th...A rat model of middle cerebral artery permanent occlusion was established using the modified Longa method. Successfully established model animals were treated by blood-letting puncture at twelve Jing-Well points of the hand, and/or by injecting mannitol into the caudal vein twice daily. Brain tissue was collected at 24, 48 and 72 hours after modeling, and blood was collected through the retinal vein before Evans blue was injected, approximately 1 hour prior to harvesting of brain tissue. Results showed that Evans blue leakage into brain tissue and serum nitric oxide synthase activity were significantly increased in model rats. Treatment with blood-letting punctures at twelve Jing-Well points of the hand and/or injection of mannitol into the caudal vein reduced the amount of Evans blue leakage into the brain tissue and serum nitric oxide synthase activity to varying degrees. There was no significant difference between single treatment and combined treatment. Experimental findings indicate that blood-letting punctures at twelve Jing-Well points of the hand can decrease blood-brain barrier permeability and serum nitric oxide synthase activity in rats following middle cerebral artery occlusion, and its effect is similar to that of mannitol injection alone and Jing-Well points plus mannitol injection.展开更多
BACKGROUND: Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influe...BACKGROUND: Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE: To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratory of Human Anatomy, Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS: Mouse anti-rat bromodeoxyuridine (BrdU) monoclonal antibody was provided by Sigma, USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase (ERK) specific inhibitor PD98059 were provided by Calbiochem, Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies, China. METHODS: A total of 126 rats were randomly assigned to four groups: model (n = 36), Du meridian (n = 36), Ren/Du meridian (n = 36), and Ren/Du meridian + PD98059 (n = 18). Rats in the Ren/Du meridian + PD98059 group were observed on days 7 (n = 6) and 14 (n = 12) after cerebral ischemia injury. Rats in the model, Du meridian, and Ren/Du meridian groups were observed on days 7, 14, and 28 after cerebral ischemia injury, with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong (DU 26) and Baihui (DU 20) acupoints in the Du meridian group, as well as Chengjiang (RN 24), Guanyuan (RN 4), Renzhong, and Baihuiacupoints in the Ren/Du meridian and Ren/Du meridian + PD98059 groups 2 days after model establishment. In addition, electro-acupuncture stimulation with disperse-dense waves was performed, with 30 Hz disperse wave, 100 Hz dense wave, and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian + PD98059 group were treated with 0.2 pg PD98059 injection into the subventricular zone, 2 pL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES: BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 (pERK1/2) expression in the subventricular zone. RESULTS: On days 14 and 28 after cerebral ischemia, there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren/Du meridian group compared with the Du meridian group (P 〈 0.05). PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the/:ten and Du meridians (P 〈 0.05). On days 7, 14, and 28 after treatment, pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group (P 〈 0.05). The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction (P 〈 0.05). However, PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression (P 〈 0.05). CONCLUSION: Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells, which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.展开更多
Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibusti...Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion (usually from 30 minutes to 1 hour) is longer than traditional suspended moxibustion (usually 15 minutes). However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebra/ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui (GV14) in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxy- lin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the in- jury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expres- sion was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.展开更多
Heat-sensitive moxibustion has neuroprotective effects against focal cerebral ischemia/reperfusion injury, however its mechanism of action remains unclear. In this study, rat models of focal cerebral ischemia/reperfus...Heat-sensitive moxibustion has neuroprotective effects against focal cerebral ischemia/reperfusion injury, however its mechanism of action remains unclear. In this study, rat models of focal cerebral ischemia/reperfusion injury were treated with suspended moxibustion at acupoint Dazhui (DU14) for 35 minutes. Results showed that suspended moxibustion decreased infarct volume, reduced cortical myeloperoxidase activity, and suppressed serum levels of proinflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings indicated that heat-sensitive moxibustion can attenuate inflammation and promote repair after focal cerebral ischemia/reperfusion injury.展开更多
Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin i...Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups: ischemia(cerebral ischemia and reperfusion), valproic acid(cerebral ischemia and reperfusion + three intraperitoneal injections of valproic acid; positive control), and baicalin(cerebral ischemia and reperfusion + intraperitoneal injection of baicalin for 21 days). Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.展开更多
Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery (MCA) occlusion by thrombus. This study aimed to characterize the model by multimodal magneti...Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery (MCA) occlusion by thrombus. This study aimed to characterize the model by multimodal magnetic resonance imaging (MRI) and to investigate its potential role for the future stroke research. Methods The left proximal MCA was embolized with an autologous thrombus in six beagles. Diffusion-weighted imaging (DWI) and T2-weighted imaging (T2Wl) were performed every half hour during the first six hours after occlusion, followed by three time points at 12 hours, 24 hours, and one week. Perfusion-weighted imaging (PWI) and magnetic resonance angiography (MRA) were carried out at six hours, 24 hours and one week. The PWI-DWI mismatch ratio was defined as (PWI-DWl)/DWl ischemic volume. Results Lacunar infarcts induced by MCA occlusion were located in the left caudate nucleus and internal capsule. All the lesions could be detected within two hours by DWI. Lesion volume on DWl increased in a time dependent manner, from (87.19±67.16) mm3 at one hour up to (368.98±217.05) mm3 at 24 hours (P=0.009), while that on PWl gradually decreased from (7315.00±2054.38) mm3at six hours to (4900.33±1319.71) mm3 at 24 hours and (3334.33±1195.11) mm3 at one week (P=0.002). The mismatch ratio was 41.93±22.75 at six hours after ischemia, showing "extensive mismatch", and decreased to 18.10±13.74 at 24 hours (P=0.002). No MCA recanalization was observed within 24 hours after MCA occlusion. Conclusions Lacunar infarction induced by proximal MCA occlusion could be detected early by DWl and was characterized by extensive PWI-DWl mismatch. Multimodal MRI is useful to demonstrate the natural evolution of PWI-DWl mismatch. This ischemic model could be further used for investigating early thrombolysis in lacunar stroke showing extensive mismatch.展开更多
Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by ...Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].展开更多
Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin wi...Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin without being in contact with it. Some researchers have used this method to treat stroke patients, but strong evidence of its therapeutic effectiveness is lacking. However, the effect of traditional suspended moxibustion has recently been improved with the development of heat-sensitive suspended moxibustion. Our previous studies showed that moxibustion for 35 min provided a more effective treatment strategy than moxibustion for 15 min, and moxibustion by 35 min with tail temperature increase had a better outcome than that without, however, the mechanism underlying the effect is not clear. In this study, we treated the stroke rats with moxibustion by 35min and divided them into non-heat sensitive moxibustion(NHSM) group and heat sensitive moxibustion (HSM) group according to difference in the tail temperature increase, then we compared the effect and investigated the mechanisms between NHSM and HSM. We found that HSM significantly decreased tail-flick latency, increased neurological function score, decreased infarct volume, reduced inflammatory cells, decreased the expression of inflammatory factor ICAM-1 and reduced the expression of NF-κB p65 and p-IKKα/β in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings revealed that HSM exerted its anti-inflammatory and neuroprotective effects from MCAO-induced injury by decreasing the expression of the NF-κB signaling pathway.展开更多
文摘BACKGROUND Diabetic ketoacidosis(DKA)is a serious complication of type 1 diabetes mellitus(T1DM).Very rarely does DKA lead to cerebral edema,and it is even rarer for it to result in cerebral infarction.Bilateral internal carotid artery occlusion(BICAO)is also rare and can cause fatal stroke.Moreover,case reports about acute cerebral infarction throughout both internal carotid arteries with simultaneous BICAO are very scarce.In this study,we present a patient with BICAO,T1DM,hypertension,and hyperlipidemia,who had a catastrophic bilateral cerebral infarction after a DKA episode.We briefly introduce BICAO and the mechanisms by which DKA results in cerebral infarction.CASE SUMMARY A 41-year-old woman presented with ischemic stroke that took place 3 mo prior over the left corona radiata,bilateral frontal lobe,and parietal lobe with right hemiplegia and Broca’s aphasia.She had a history of hypertension for 5 years,hyperlipidemia for 4 years,hyperthyroidism for 3 years,and T1DM for 31 years.The first brain magnetic resonance imaging not only revealed the aforementioned ischemic lesions but also bilateral internal carotid artery occlusion.She was admitted to our ward for rehabilitation due to prior stroke sequalae.DKA took place on hospital day 2.On hospital day 6,she had a new massive infarction over the bilateral anterior cerebral artery and middle cerebral artery territory.After weeks of aggressive treatment,she remained in a coma and on mechanical ventilation due to respiratory failure.After discussion with her family,compassionate extubation was performed on hospital day 29 and she died.CONCLUSION DKA can lead to cerebral infarction due to several mechanisms.In people with existing BICAO and several stroke risk factors such as hypertension, T1DM,hyperlipidemia, DKA has the potential to cause more serious ischemic strokes.
文摘The use of operating microscopes is limited by the focal length.Surgeons using these instruments cannot simultaneously view and access the surgical field and must choose one or the other.The longer focal length (more than 1 000 mm) of an operating telescope permits a position away from the operating field,above the surgeon and out of the field of view.This gives the telescope an advantage over an operating microscope.We developed a telescopic system using screen-imaging guidance and a modified portable video macroscope constructed from a Computar MLH-10 × macro lens,a DFK-21AU04 USB CCD Camera and a Dell laptop computer as monitor screen.This system was used to establish a middle cerebral artery occlusion model in rats.Results showed that magnification of the modified portable video macroscope was appropriate (5-20 ×) even though the Computar MLH-10 × macro lens was placed 800 mm away from the operating field rather than at the specified working distance of 152.4 mm with a zoom of 1-40 ×.The screen-imaging telescopic technique was clear,life-like,stereoscopic and matched the actual operation.Screen-imaging guidance led to an accurate,smooth,minimally invasive and comparatively easy surgical procedure.Success rate of the model establishment evaluated by neurological function using the modified neurological score system was 74.07%.There was no significant difference in model establishment time,sensorimotor deficit and infarct volume percentage.Our findings indicate that the telescopic lens is effective in the screen surgical operation mode referred to as "long distance observation and short distance operation" and that screen-imaging guidance using an modified portable video macroscope can be utilized for the establishment of a middle cerebral artery occlusion model and micro-neurosurgery.
基金supported by Zhejiang Province Science and Technology Plan Project in China,No.2012C37029Public Welfare Technology Application Research Plan Project of Zhejiang Province in China,No.2011C23021
文摘Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffu- sion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially in- creased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion co- efficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at remote regions (cerebellum) varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis.
文摘The present study aimed to verify the practicability of performing screen-based surgical operations under the guidance of a real-time viewing and recording system (RTVRS) using a portable medium-soft electronic endoscope (pmsEE). The middle cerebral artery in rats was occluded under screen-imaging guidance using a pmsEE RTVRS to reproduce an animal model of human cerebral infarction. The screen imaging of the pmsEE RTVRS was clear, life-like, stereoscopic and synchronous with the actual operation. Screen-imaging guidance led to an accurate, smooth, minimally invasive and comparatively easy surgical procedure. The surgical success rate, time of model establishment, neurological function scores, and infarct volume were similar to those using an operating microscope. These results indicate that the self-designed pmsEE RTVRS could be utilized for portable endoscopic screen-based surgical operations.
基金supported by the National Natural Science Foundation of China,No.30960399,and No.81160181
文摘In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes (T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]) following cerebral infarction. The pathological changes were divided into three phases: early cerebral infarction, middle cerebral infarction, and late cerebral infarction. In the early cerebral infarction phase (less than 2 hours post-infarction), there was evidence of intracellular edema, which improved after reperfusion. This improvement was defined as the ischemic penumbra. In this phase, a high DWI signal and a low apparent diffusion coefficient were observed in the right basal ganglia region. By contrast, there were no abnormal T2WI and T2FLAIR signals. For the middle cerebral infarction phase (2-4 hours post-infarction), a mixed edema was observed. After reperfusion, there was a mild improvement in cell edema, while the angioedema became more serious. A high DWI signal and a low apparent diffusion coefficient signal were observed, and some rats showed high T2WI and T2FLAIR signals. For the late cerebral infarction phase (4-6 hours post-infarction), significant angioedema was visible in the infarction site. After reperfusion, there was a significant increase in angioedema, while there was evidence of hemorrhage and necrosis. A mixed signal was observed on DWI, while a high apparent diffusion coefficient signal, a high T2WI signal, and a high T2FLAIR signal were also observed. All 86 cerebral infarction patients were subjected to T2WI, T2FLAIR, and DWI. MRI results of clinic data similar to the early infarction phase of animal experiments were found in 51 patients, for which 10 patients (10/51) had an onset time greater than 6 hours. A total of 35 patients had MRI results similar to the middle and late infarction phase of animal experiments, of which eight patients (8/35) had an onset time less than 6 hours. These data suggest that defining the "therapeutic time window" as the time 6 hours after infarction may not be suitable for all patients. Integrated application of MRI sequences including T2WI, T2FLAIR, DW-MRI, and apparent diffusion coefficient mapping should be used to examine the ischemic penumbra, which may provide valuable information for identifying the "therapeutic time window".
文摘BACKGROUND: Previously, only single short-time low-dose hyperbaric oxygenation (HBO) protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time (can cover all the natural pathologic progression period) high-dose HBO to treat the disease. OBJECTIVE: To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion (MCAO) in rats. DESIGN: A randomized controlled experimental study. SETTING: Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS: Seventy-four male SD rats, aged 2.5 months old, weighing ( 280 + 20) g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin (made in China). METHODS: This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention: All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups (9 hours and 18 hours) and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours l, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, l0 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation: Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES: ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS: ① Neurobehavioral outcome: After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group (P 〈 0.01). Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group (P 〈 0.01). ② Cerebral infarct volume: Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling (P 〈 0.01). In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling (P 〈 0.05). ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION: High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.
文摘We investigated the effects of ipsilateral versus bilateral limb-training on promotion of endogenous neural stem cells in the peripheral infarct zone and the corresponding cerebral region in the unaffected hemisphere of rats with cerebral infarction. Middle cerebral artery occlusion was induced in Wistar rats. The rat forelimb on the unaffected side was either wrapped up with tape to force the use of the paretic forelimb in rats or not braked to allow bilateral forelimbs to participate in training. Daily training consisted of mesh drum training, balance beam training, and stick rolling training for a total of 40 minutes, once per day. Control rats received no training. At 14 days after functional training, rats receiving bilateral limb-training exhibited milder neurological impairment than that in the ipsilateral limb-training group or the control group. The number of nestin/glial fibrillary acidic protein-positive and nestin/microtubule-associated protein 2-positive cells in the peripheral infarct zone and in the corresponding cerebral region in the unaffected hemisphere was significantly higher in rats receiving bilateral limb-training than in rats receiving ipsilateral limb-training. These data suggest that bilateral limb-training can promote the proliferation and differentiation of endogenous neural stem cells in the bilateral hemispheres after cerebral infarction and accelerate the recovery of neurologic function. In addition, bilateral limb-training produces better therapeutic effects than ipsilateral limb-training.
文摘Acute aortic dissection is a life-threatening condition requiring immediate assessment and therapy. Rarely, aortic dis-section involves carotid arteries and manifest cerebral infarction. Here, we report a case of aortic dissection complicated with fatal cerebral infarction. A 83-year-old man, who suddenly suffered consciousness disturbance and right hemiparesis, was transferred to our hospital for the treatment of stroke. Magnetic resonance image revealed massive cerebral infarction in the left cerebral hemisphere as well as occlusion of the left internal carotid artery. Duplex ultrasonography demonstrated arterial dissection in the bilateral carotid arteries and the blood flow was compromised especially in the left side. Aortic dissection was confirmed by the contrast enhanced computed tomography. He was treated conservatively and died of cerebral hernia three days after the onset. In conclusion, aortic dissection may involve carotid artery and results in cerebral infarction. Ultrasound screening can aid timely diagnosis of aortic dissection and further management.
文摘In multiple trauma, blunt carotid artery injuries (BCAIs) have occasionally been reported. However, bilateral blunt carotid artery occlusions (Grade 4 BCAIs) associated with multiple trauma are rare, and delays in diagnosis and treatment result in a lethal outcome. Here, we report our experience with bilateral carotid artery occlusions. A 76-year-old female suffered multiple traumas in a motor vehicle accident. On arrival at our hospital, she presented in a coma, with left mydriasis and unreactive pupils. Computed tomography (CT) showed bifrontal intracranial epidural hematoma and fractures of the facial bone and anterior skull base, and osteoplastic craniotomy was urgently undertaken for the epidural hematoma. However, the comatose state and unreactive pupils persisted during the post-operative course. Serial head CT findings showed progressive bilateral ischemic changes, and radiological examinations revealed bilateral internal carotid artery occlusions. We speculated that bilateral Grade 4 BCAIs had induced progressive cerebral infarctions. The patient partially responded to anticoagulation therapy with heparin infusion, but died of multiple organ failure on day 15. When bilateral progressive ischemic changes are observed in a patient with severe traumatic brain injury, bilateral Grade 4 BCAIs should be considered in the differential diagnosis. CT angiography as part of whole-body CT at admission may be effective for preventing delays in diagnosis and treatment of bilateral Grade 4 BCAIs.
文摘The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with fructose 1,6 diphosphate (FDP) 200 and 350 mg·kg 1 ip immediately after MCAO, respectively, significantly reduced the infarction area and volume in a dose dependent manner. MK801 and FDP also displayed a protective effect on brain ischemia. A combination of Tet and FDP administered immediately after MCAO, produced a more potent protective effect than those treated with Tet or FDP alone. When Tet or FDP was administered 1 h and 2 h after MCAO, respectively, they could still significantly reduce the infarction area and volume of brain tissue. But, there was no significant protective effect when these two compounds were given 3 h after MCAO.
基金sponsored by the Open Research Fund of Zhejiang First-foremost Key Subject-Acupuncture & Moxibustion,No. ZTK2010A07
文摘A rat model of middle cerebral artery permanent occlusion was established using the modified Longa method. Successfully established model animals were treated by blood-letting puncture at twelve Jing-Well points of the hand, and/or by injecting mannitol into the caudal vein twice daily. Brain tissue was collected at 24, 48 and 72 hours after modeling, and blood was collected through the retinal vein before Evans blue was injected, approximately 1 hour prior to harvesting of brain tissue. Results showed that Evans blue leakage into brain tissue and serum nitric oxide synthase activity were significantly increased in model rats. Treatment with blood-letting punctures at twelve Jing-Well points of the hand and/or injection of mannitol into the caudal vein reduced the amount of Evans blue leakage into the brain tissue and serum nitric oxide synthase activity to varying degrees. There was no significant difference between single treatment and combined treatment. Experimental findings indicate that blood-letting punctures at twelve Jing-Well points of the hand can decrease blood-brain barrier permeability and serum nitric oxide synthase activity in rats following middle cerebral artery occlusion, and its effect is similar to that of mannitol injection alone and Jing-Well points plus mannitol injection.
基金the National Natural Science Foundation of China,No.30371808the Natural Science Foundation of Guangdong Province,No.5009688
文摘BACKGROUND: Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However, there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE: To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratory of Human Anatomy, Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS: Mouse anti-rat bromodeoxyuridine (BrdU) monoclonal antibody was provided by Sigma, USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase (ERK) specific inhibitor PD98059 were provided by Calbiochem, Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies, China. METHODS: A total of 126 rats were randomly assigned to four groups: model (n = 36), Du meridian (n = 36), Ren/Du meridian (n = 36), and Ren/Du meridian + PD98059 (n = 18). Rats in the Ren/Du meridian + PD98059 group were observed on days 7 (n = 6) and 14 (n = 12) after cerebral ischemia injury. Rats in the model, Du meridian, and Ren/Du meridian groups were observed on days 7, 14, and 28 after cerebral ischemia injury, with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong (DU 26) and Baihui (DU 20) acupoints in the Du meridian group, as well as Chengjiang (RN 24), Guanyuan (RN 4), Renzhong, and Baihuiacupoints in the Ren/Du meridian and Ren/Du meridian + PD98059 groups 2 days after model establishment. In addition, electro-acupuncture stimulation with disperse-dense waves was performed, with 30 Hz disperse wave, 100 Hz dense wave, and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian + PD98059 group were treated with 0.2 pg PD98059 injection into the subventricular zone, 2 pL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES: BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 (pERK1/2) expression in the subventricular zone. RESULTS: On days 14 and 28 after cerebral ischemia, there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren/Du meridian group compared with the Du meridian group (P 〈 0.05). PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the/:ten and Du meridians (P 〈 0.05). On days 7, 14, and 28 after treatment, pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group (P 〈 0.05). The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction (P 〈 0.05). However, PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression (P 〈 0.05). CONCLUSION: Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells, which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.
基金supported by the National Natural Science Foundation of China,No.81060305&81660819the Natural Science Foundation of Jiangxi Province of China,No.2015BAB205068+2 种基金Key Program for Science and Technology Cooperation Projects of Jiangxi Province of China,No.20161BBH80053a grant from the Key Project of Health Commission of Jiangxi Province of China,No.2014Z003the Natural Science Foundation of Jiangxi University of Traditional Chinese Medicine of China,No.2014ZR018&2015jzzdxk024
文摘Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion (usually from 30 minutes to 1 hour) is longer than traditional suspended moxibustion (usually 15 minutes). However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebra/ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui (GV14) in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxy- lin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the in- jury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expres- sion was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.
基金supported by the National Natural Science Foundation of China, No. 81060305
文摘Heat-sensitive moxibustion has neuroprotective effects against focal cerebral ischemia/reperfusion injury, however its mechanism of action remains unclear. In this study, rat models of focal cerebral ischemia/reperfusion injury were treated with suspended moxibustion at acupoint Dazhui (DU14) for 35 minutes. Results showed that suspended moxibustion decreased infarct volume, reduced cortical myeloperoxidase activity, and suppressed serum levels of proinflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings indicated that heat-sensitive moxibustion can attenuate inflammation and promote repair after focal cerebral ischemia/reperfusion injury.
基金supported by the Cross Foundation Major Project of Engineering and Medicine of Shanghai Jiao Tong University,No.YG2016MS50(to JD)Foundation for Fostering Project of Clinical Study on Multi-disciplinary Team of Renji Hospital,No.PYMDT-012(to JD)
文摘Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups: ischemia(cerebral ischemia and reperfusion), valproic acid(cerebral ischemia and reperfusion + three intraperitoneal injections of valproic acid; positive control), and baicalin(cerebral ischemia and reperfusion + intraperitoneal injection of baicalin for 21 days). Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.
基金This study was supported by the National Natural Science Foundation of China (No. 30870710, No. 81000653) and the Foundation of Research and Innovation Program for Postgraduates in Jiangsu Province (No. CXZZll.0718).
文摘Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery (MCA) occlusion by thrombus. This study aimed to characterize the model by multimodal magnetic resonance imaging (MRI) and to investigate its potential role for the future stroke research. Methods The left proximal MCA was embolized with an autologous thrombus in six beagles. Diffusion-weighted imaging (DWI) and T2-weighted imaging (T2Wl) were performed every half hour during the first six hours after occlusion, followed by three time points at 12 hours, 24 hours, and one week. Perfusion-weighted imaging (PWI) and magnetic resonance angiography (MRA) were carried out at six hours, 24 hours and one week. The PWI-DWI mismatch ratio was defined as (PWI-DWl)/DWl ischemic volume. Results Lacunar infarcts induced by MCA occlusion were located in the left caudate nucleus and internal capsule. All the lesions could be detected within two hours by DWI. Lesion volume on DWl increased in a time dependent manner, from (87.19±67.16) mm3 at one hour up to (368.98±217.05) mm3 at 24 hours (P=0.009), while that on PWl gradually decreased from (7315.00±2054.38) mm3at six hours to (4900.33±1319.71) mm3 at 24 hours and (3334.33±1195.11) mm3 at one week (P=0.002). The mismatch ratio was 41.93±22.75 at six hours after ischemia, showing "extensive mismatch", and decreased to 18.10±13.74 at 24 hours (P=0.002). No MCA recanalization was observed within 24 hours after MCA occlusion. Conclusions Lacunar infarction induced by proximal MCA occlusion could be detected early by DWl and was characterized by extensive PWI-DWl mismatch. Multimodal MRI is useful to demonstrate the natural evolution of PWI-DWl mismatch. This ischemic model could be further used for investigating early thrombolysis in lacunar stroke showing extensive mismatch.
基金supported by Health and Medical Research Fund,the Food and Health Bureau,The Government of the Hong Kong Special Administrative Region(03142256)General Research Fund,Hong Kong Research Grants Council(GRF#HKU773613M)+1 种基金Seed Funding Programme for Basic Research(201811159123,201910159191)The University of Hong Kong(all to ACYL)。
文摘Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].
基金We would like to thank the National Natural Science Foun dation of China (81060305, 81660819)the Natural Science Foundation of Jiangxi Province (20151BAB205068), Key Project of Health Commission of Jiangxi province (2014Z003)Natural Science Foundation of Jiangxi University of Traditional Chinese Medicine (2014ZR018,- 2015jzzdxk024) for their supports.
文摘Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin without being in contact with it. Some researchers have used this method to treat stroke patients, but strong evidence of its therapeutic effectiveness is lacking. However, the effect of traditional suspended moxibustion has recently been improved with the development of heat-sensitive suspended moxibustion. Our previous studies showed that moxibustion for 35 min provided a more effective treatment strategy than moxibustion for 15 min, and moxibustion by 35 min with tail temperature increase had a better outcome than that without, however, the mechanism underlying the effect is not clear. In this study, we treated the stroke rats with moxibustion by 35min and divided them into non-heat sensitive moxibustion(NHSM) group and heat sensitive moxibustion (HSM) group according to difference in the tail temperature increase, then we compared the effect and investigated the mechanisms between NHSM and HSM. We found that HSM significantly decreased tail-flick latency, increased neurological function score, decreased infarct volume, reduced inflammatory cells, decreased the expression of inflammatory factor ICAM-1 and reduced the expression of NF-κB p65 and p-IKKα/β in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings revealed that HSM exerted its anti-inflammatory and neuroprotective effects from MCAO-induced injury by decreasing the expression of the NF-κB signaling pathway.