Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine fetal distress

BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that timely interventions can be implemented to safeguard the health and safety of the fetus.AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress.METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups(n=50 each),according to the presence or absence of intrauterine distress.The ultrasound hemodynamic parameters of the uterine artery(UtA),fetal middle cerebral artery(MCA),and umbilical artery(UmA)were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups.RESULTS Comparison of ultrasonic hemodynamic parameters,resistance index(RI),pulsatility index(PI),and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity(S/D),revealed higher values of fetal MCA,PI,and S/D of UmA in pregnant women with UtA compared to controls(P<0.05),while there was no difference between the two groups in terms of RI(P<0.05)The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group(66.7%)than in the control group(90.0%),and neonatal weight(2675.5±27.6 g)was lower than in the control group(3117.5±31.2 g).Further,cesarean section rate was higher in the observation group(70.0%)than in the control group(11.7%),and preterm labor rate was higher in the observation group(40.0%)than in the control group(10.0%).The incidence of fetal distress,neonatal growth restriction and neonatal asphyxia were also higher in the observation group(all P<0.05).CONCLUSION Fetal MCA,UmA,and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy,which suggests that clinical attention should be paid to them,and monitoring should be strengthened to provide guidance for clinical intervention.

Drug-coated balloon angioplasty for the treatment of intracranial arterial stenosis in a young stroke patient:A case report

BACKGROUND Intracranial arterial narrowing is a significant factor leading to brief episodes of reduced blood flow to the brain,known as transient ischemic attacks,or fullblown strokes.While atherosclerosis is commonly associated with intracranial arterial narrowing,it is frequently of a non-atherosclerotic nature in younger patients.CASE SUMMARY Here,we present the case of a young stroke patient with narrowing of the middle cerebral artery(MCA),characterized as non-atherosclerotic lesions,who experienced an ischemic stroke despite receiving standard drug therapy.The patient underwent digital subtraction angiography(DSA)to assess the entire network of blood vessels in the brain,revealing significant narrowing(approximately 80%)in the M1 segment of the right MCA.Subsequently,the patient underwent Drug-Coated Balloon Angioplasty to treat the stenosis in the right MCA's M1 segment.Follow-up DSA confirmed the resolution of stenosis in this segment.Although the remaining branches showed satisfactory blood flow,the vessel wall exhibited irregularities.A review of DSA conducted six months later showed no evident stenosis in the right MCA,with a smooth vessel wall.CONCLUSION The use of drug-coated balloon angioplasty demonstrated favorable outcomes in repairing and reshaping the blood vessel wall in young patients.Therefore,it may be considered a promising treatment option for similar cases.

Vav1 promotes inflammation and neuronal apoptosis in cerebral ischemia/reperfusion injury by upregulating microglial and NLRP3 inflammasome activation

Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.

DNA hypomethylation promotes learning and memory recovery in a rat model of cerebral ischemia/reperfusion injury

Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.

Effects of L-Tetrahydropalmatine on NOSⅢ Gene Expression in Hypoxia and Cultured Porcine Cerebral Arterial Endothelial Cells during Reoxygenation

To investigate the expression of NOSⅢ mRNA and protein in cultured porcine cerebral arterial endothelial cells (CAEC) during hypoxia and reoxygenation and the effects of L-Tetrahydropalmatine (L-THP) on the gene expression of NOSⅢ in CAEC during hypoxia and reoxygenation. The cultured CAEC were divided into 5 groups: control, hypoxia, hypoxia+reoxygenation, hypoxia+L-THP and reoxygenation+L-THP groups. NOSⅢ mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunocytochemistry was used to detect the level of NOSⅢ protein. The expression of NOSⅢ mRNA and protein were increased when CAEC were exposed to hypoxia for 1 h, and significantly decreased during reoxygenation 2, 6 and 12 h after 1-h of hypoxia. L-THP from 10 -8 mol/L to 10 -3 mol/L could inhibit the up-regulation of NOSⅢ gene expression during hypoxia and down-regulation of NOSⅢ gene expression during reoxygenation.

Relationship of cerebral arterial stenosis to cognitive and memory disorders

BACKGROUND: Cerebral arterial stenosis can cause cerebral hypoperfusion, and than result in the decline of cognitive function, whereas the cognitive dysfunction induced by different cerebral arterial stenosis have different manifestations and types. OBJECTIVE: To observe the differences of cognitive and memory dysfunctions in patients with cerebral arterial stenosis of different types. DESIGN: A comparative observation. SETTING: Affiliated Hospital of Jining Medical College. PARTICIPANTS: Forty-two outpatients or inpatients with cerebral arterial stenosis were selected from the Department of Neurology, Affiliated Hospital of Jining Medical College from February 2005 to January 2006, including 25 males and 17 females. There were 18 cases of internal carotid arterial stenosis, 14 cases of vertebrobasilar arterial stenosis and 10 cases of whole cerebral arterial stenosis. The diagnostic standards for cerebral arterial stenosis were identified according to North American Symptomatic Carotid Endarterectomy Trial (NASCET). Meanwhile, 18 healthy physical examinees were enrolled as the control group, including 10 males and 8 females, aged 58-80 years old. All the enrolled subjects were informed and agreed with the detection and evaluation. METHODS: ① The memory function was evaluated using revised Wechsler memory scale for adults, including long-term memory (experience, orientation and counting), short-term memory (visual recognition, picture memory, visual regeneration, association and thigmesthesia) and sensory memory (forward and backward recitation of numbers). The scale scores were turned to memory quotients. The higher the scores, the better the memory function. ② The cognitive function was evaluated using revised Wechsler adult intelligence scale: It consisted of eleven subtests, including six language scales (information, digit span, vocabulary, arithmetics, apprehension, similarity) and five operation scales (picture completion, picture arrangement, block design, geometric design, digit-symbol test). The intelligence quotients were obtained. The higher the scores, the better the cognitive function. MAIN OUTCOME MEASURES: Results of memory and cognitive function test in patients with cerebral arterial stenosis of different types. RESULTS: All the 42 patients with cerebral artery stenosis and 11 healthy subjects were involved in the final analysis of results. ① Results of memory function test: The memory function was worse in the arterial stensis groups than in the control group (P < 0.05-0.01). There were very significant differences in the scores of orientation, association and picture memory between the internal carotid arterial stenosis group and control group (P < 0.01). There were also very significant differences in the scores of counting, logic memory, forward and backward recitation of numbers, visual regeneration, visual recognition and thigmesthesia between the vertebrobasilar arterial stenosis group and control group (P < 0.01). Except experience and visual regeneration, there were significant very differences in the scores of the other tests between the whole cerebral arterial stenosis group and control group (P < 0.01). The memory quotient was obviously lower in the vertebrobasilar arterial stenosis group than in the internal carotid arterial stenosis group [(72.31±26.46), (87.38±21.86) points, P < 0.05], and it was the lowest in the whole cerebral arterial stenosis group [(63.74±25.25) points]. ② Results of cognitive function test: The cognitive function was worse in the arterial stensis groups than in the control group (P < 0.05-0.01). There were very significant differences in the scores of apprehension, arithmetics, similarity, digit-symbol test, picture completion and block design between the internal carotid arterial stenosis group and control group (P < 0.01). There were also very significant differences in the scores of backward recitation of numbers, vocabulary and geometric design between the vertebrobasilar arterial stenosis group and control group (P < 0.01). Except information, there were significant very differences in the scores of the other tests between the whole cerebral arterial stenosis group and control group (P < 0.01). The intelligence quotient was obviously lower in the internal carotid arterial stenosis group than in the vertebrobasilar arterial stenosis group [(72.65±23.39), (81.34±25.46) points, P < 0.05], and it was the lowest in the whole cerebral arterial stenosis group [(65.98±27.34) points]. CONCLUSION: Different cerebral arterial stenosis can induce different cognitive dysfunctions. The main manifestation of the patients with internal carotid arterial stenosis was the declined cognitive function, and that in patients with vertebrobasilar arterial stenosis was the declined memory, and the decrease of total intelligence was more obvious in the formers than in the latters, whereas the decrease of total memory quotient was more obvious in the patients with vertebrobasilar arterial stenosis; The cognitive and memory dysfunction were the most serious in patients with whole cerebral arterial stenosis.

Doppler examination and cerebral arterial stricture in patients with ischemic stroke

BACKGROUND: With the development of interventional therapy, it is necessary for evaluating cerebral vessels to instruct treatment and determine prognosis of patients with ischemic stroke; however, correlation of distribution of infarction focus and clinical symptoms with degrees of cerebrovascular stricture is still unclear. OBJECTIVE: To evaluate the characteristics of cerebral arterial stricture of patients with ischemic stroke with transcranial Doppler (TCD) and color duplex flow imaging (CDFI) and compare the correlation between distribution of cerebral infarction focus and clinical types with magnetic resonance imaging (MRI). DESIGN: Contrast observation. SETTING: Department of Neurology, the First Hospital of Jilin University. PARTICIPANTS: A total of 159 patients with ischemic stroke were selected from the Department of Neurology, the First Hospital of Jilin University from January to December 2005, including 106 males and 53 females aged from 27 to 88 years. Bases on diagnostic criteria of cerebrovascular disease established by Rao et al, clinical manifestations of all patients were evaluated with CT or nuclear magnetic resonance. All patients provided the confirmed consent. METHODS: The accepted patients received TCD and CDFI examination at 1 week after onset of ischemic stroke. Among them, 112 patients received cerebrovascular imaging examination simultaneously. MRI was used to check cerebral infarction focus and cerebrovascular stricture > 50% was regarded as the accepted vessels. In addition, DWI-T2 TCD (Germany) was used to check middle cerebral artery, and degrees of middle cerebral artery were classified into mild, moderate and severe stricture based on blood velocity (140 cm/s, 180 cm/s). Stroke was classified based on characteristics of infarction focus and clinical symptoms showed with MRI and correlation with degrees of cerebrovascular stricture was analyzed simultaneously. MAIN OUTCOME MEASURES: Correlation between the characteristics of ischemic stroke and clinical symptoms checked with TCD and CDFI. RESULTS: A total of 159 patients with ischemic stroke were involved in the final analysis; in addition, 112 cases received cerebrovascular imaging examination simultaneously. ① MRI results of 159 patients with cerebral artery occlusive disease (CAOD): There were 131 patients (82.3%) with cerebral infarction, 40 (25.2%) with transient ischemic attack and 4 (2.5%) with subclavian steal syndrome (SSS). ② Infarction types with MRI examination: There were 33 patients (20.8%) with solitary cerebral infarction and 98 (61.6%) with multiple-cerebral infarction. ③ Results of TCD, CDFI, MRI angiography, CT angiography and digital subtraction angiography (DSA): Among 112 patients, 181 lesion sites (61.8%) were located in cranium and 112 lesion sites were located out of cranium; especially, lesion site was mostly observed in stem of middle cerebral artery (31.2%) and watershed of basilar artery (7.2%) in cranium and the beginning site of internal carotid artery (21.4%) out of cranium. ④ Correlation of vascular stricture checking with TCD, MRI and clinical diagnosis: On one hand, MRI and clinical diagnosis demonstrated that 68 patients had a watershed infarction; meanwhile, TCD examination indicated that there were 3 patients with mild vascular stricture, 24 with moderate vascular stricture and 36 with severe vascular stricture. On the other hand, among 68 patients with non-watershed infarction, there were 27 patient with mild vascular stricture, 26 with moderate vascular stricture and 15 with severe vascular stricture. There were significant differences (χ2 =26.854, P =0.001). Clinical diagnosis indicated that 40 patients had transient ischemic attack and TCD examination demonstrated that there were 8 patient with mild vascular stricture, 12 with moderate vascular stricture and 20 with severe vascular stricture. There were significant differences as compared with 68 patients with watershed infarction (χ2 =21.258, P =0.001). ⑤ Correlation of vascular stricture checking with CDFI, MRI and clinical diagnosis: On one hand, among patients who were determined as watershed infarction with MRI and clinical diagnosis, CDFI examination indicated that there were 32 patients with mild vascular stricture at neck, 25 with moderate vascular stricture and 6 with severe vascular stricture. On the other hand, among patients with non-watershed infarction, there were 48 patient with mild vascular stricture, 18 with moderate vascular stricture and 2 with severe vascular stricture. There were significant differences (χ2 =6.018, P =0.019). Among patients with transient ischemic attack checking with clinical diagnosis, there were 23 patient with mild vascular stricture, 9 with moderate vascular stricture and 8 with severe vascular stricture. There were no significant differences as compared with patients with non-watershed infarction (χ2 =0.597, P =0.440). CONCLUSION: ① TCD and CDFI are effective marks to determine cerebral arterial stricture and hemodynamical changes. ② Infarction and transient ischemic attack at watershed are generally clinical phenotypes of CAOD patients and infarction at watershed is correlated with degrees of cerebrovascular stricture. ③ TCD, MRI and clinical analysis of stroke types are significant for instructing treatment and evaluate prognosis.

Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

BACKGROUND: Ankle brachial index (ABI) is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes mellitus (DM); however, the application in cerebral infarction (CI) is rare. OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease (PAD), compare metabolic characteristics of patients who having CI plus PAD or only having CI, and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb. DESIGN: Contrast observation based on CI patients. SETTING: Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region. PARTICIPANTS: A total of 124 CI patients were selected from Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006, including 72 males and 52 females aged from 45 to 88 years. All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination. All patients provided informed consent. There were 46 cases (37.2%) with CI plus PAD and 78 cases (62.8%) only with CI. METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor (GE Company). The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI. The normal ABI was equal to or more than 0.9. If ABI < 0.9 occurred at one side, patients were diagnosed as PAD. On the second morning after hospitalization, blood was collected to measure fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG2h), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Among them, blood glucose, lipid and other biochemical markers were measured with enzyme chemistry assay and HbA1c was measured with HbA1c meter based on high liquid phase. Measurement data and enumeration data were compared with t test and Chi-square test, and multiple factors were dealt with Logistic regression analysis and multivariate linear regression analysis. MAIN OUTCOME MEASURES: Results of correlation between ABI and metabolic markers with multivariate linear regression analysis; risk factors of CI plus PAD with Logistic regression analysis; comparisons of metabolic markers between PAD and non-PAD patients. RESULTS: All 124 patients with acute CI were involved in the final analysis. ① Comparisons of metabolic markers: Levels of serum LDL-C and uric acid (UA) were higher of PAD patients than those of non-PAD patients (t =2.051 9, 3.339 1, P < 0.05); however, there were no significant differences among other metabolic markers (P > 0.05). ② Results of multivariate linear regression analysis: PBG2h, LDL-C and UA were obvious correlation with ABI of posterior tibial artery of lower limb and dorsal pedis artery (partial regression coefficient = -0.231 to -1.010, P < 0.05). ③ Risk factors of CI plus PAD with Logistic regression analysis: Age, smoking history, sum of CI focus (≥3) and LDL-C were independent risk factor of CI plus PAD (OR =1.524-5.422, P < 0.05-0.01). CONCLUSION: ① Levels of serum LDL-C and UA of patients with CI plus PAD are high. ② ABI of lower limbs is correlation with PBG2h, LDL-C and UA. In addition, measuring ABI is beneficial for early diagnosing PAD of lower limbs of patients who have poorly controlled blood glucose, abnormal lipid and poor renal function. ③ Age, LDL-C and sum of CI focus (≥3) are independent risk factors of CI plus PAD. It is of significance for screening non-PAD patients to evaluate risk degrees and prognosis and select therapeutic methods based on ABI measurement.

A molecular probe carrying anti-tropomyosin 4 for early diagnosis of cerebral ischemia/reperfusion injury

In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.

Clinical Analysis of Embryonic Posterior Cerebral Artery

Objective:To understand the clinical characteristics of patients with embryonic posterior cerebral artery and its correlation with abnormal vascular development.Methods:The clinical data of 396 patients with embryonic posterior cerebral artery confirmed by magnetic resonance angiography(MRA)and computed tomography angiography(CTA)were analyzed.Results:Two-hundred patients had clinical manifestations of posterior circulation ischemia,including recurrent dizziness,vertigo,and tinnitus;45 had headaches,97 had limb weakness,and 16 patients had syncope or impaired consciousness.Seventy-six patients with circulatory infarction were admitted to the hospital.There were 251 patients with history of hypertension,74 with diabetes,113 with hyperlipidemia,13 with dominant vertebral artery,10 with intracranial aneurysm,and 19 with absence of A1 segment of the anterior cerebral artery(considering developmental variation).Conclusion:Embryonic posterior cerebral artery develops abnormally during the embryonic period,often accompanied by abnormal vascular access.Due to abnormal hemodynamics,the incidence of posterior circulation ischemia,aneurysm,and infarction increases in such patients.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.

Endovascular treatment of ruptured lobulated anterior communicating artery aneurysms:A retrospective study of 24 patients

BACKGROUND Lobulated intracranial aneurysm is a special type of aneurysm with at least one additional cyst in the neck or body of the aneurysm.Lobulated intracranial aneurysm is a complex aneurysm with complex morphology and structure and weak tumor wall,which is an independent risk factor for rupture and hemorrhage.Lobular aneurysms located in the anterior communicating artery complex account for 36.9%of all intracranial lobular aneurysms.Due to its special anatomical structure,both craniotomy and endovascular treatment are more difficult.Compared with single-capsule aneurysms,craniotomy for lobular intracranial aneurysms has a higher risk and complication rate.AIM To investigate the efficacy and safety of endovascular treatment for ruptured lobulated anterior communicating artery aneurysm(ACoAA).METHODS Patients with ruptured lobulated ACoAA received endovascular treatment in Sanming First Hospital Affiliated to Fujian Medical University from June 2020 to June 2022 were retrospectively included.Their demographic,clinical and imaging characteristics,endovascular treatment methods and follow-up results were collected.RESULTS A total of 24 patients with ruptured lobulated ACoAA were included,including 9 males(37.5%)and 15 females(62.5%).Their age was 56.2±8.9 years old(range 39-74).The time from rupture to endovascular treatment was 10.9±12.5 h.The maximum diameter of the aneurysms was 5.1±1.0 mm and neck width were 3.0±0.7 mm.Nineteen patients(79.2%)were double-lobed and 5(20.8%)were multilobed.Fisher's grade:Grade 2 in 16 cases(66.7%),grade 3 in 6 cases(25%),and grade 4 in 2 cases(8.3%).Hunt-Hess grade:Grade 0-2 in 5 cases(20.8%),grade 3-5 in 19 cases(79.2%).Glasgow Coma Scale score:9-12 in 14 cases(58.3%),13-15 in 10 cases(41.7%).Immediately postprocedural Raymond-Roy grade:grade 1 in 23 cases(95.8%),grade 2 in 1 case(4.2%).Raymond-Roy grade in imaging follow-up for 2 wk to 3 months:grade 1 in 23 cases(95.8%),grade 2 in 1 case(4.2%).Followup for 2 to 12 months showed that 21 patients(87.5%)had good functional outcomes(modified Rankin Scale score≤2),and there were no deaths.CONCLUSION Endovascular treatment is a safe and effective treatment for ruptured lobulated AcoAA.

Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.

Inflammatory response and neuronal necrosis in rats with cerebral ischemia

In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap- peared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia,

Therapeutic effects of different durations of acupuncture on rats with middle cerebral artery occlusion

Acupuncture is regarded as an effective therapy for cerebral ischemia. Different acupuncture ma- nipulations and durations may result in different therapeutic effects. In the present study, the Neig uan （PC6） acupoint of rats with occluded middle cerebral arteries was needled at a fixed frequency （3 Hz） with different durations, i.e., 5, 60 and 180 seconds under a twisting-rotating acupuncture method. Results showed that different durations of acupuncture had different therapeutic effects, with 60 seconds yielding a better therapeutic effect than the other two groups. This duration of treatment demonstrated rapid cerebral blood flow, encouraging recovery of neurological function, and small cerebral infarct volume. Experimental findings indicated that under 3 Hz frequency, the treatment of needling Neiguan for 60 seconds is effective for ischemic stroke.

Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies

Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all the components of PANoptosis to be regulated simultaneously.PANoptosis provides a new way to study the regulation of cell death,in that different types of cell death may be regulated at the same time.To test whether PANoptosis exists in diseases other than infectious diseases,we chose cerebral ischemia/reperfusion injury as the research model,collected articles researching cerebral ischemia/reperfusion from three major databases,obtained the original research data from these articles by bibliometrics,data mining and other methods,then integrated and analyzed these data.We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion.In the cell model simulating ischemic brain injury,pyroptosis,apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons.Pyroptosis,apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury.This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.

Influence of Ren and Du meridian electro-acupuncture on neural stem cell proliferation and extracellular signal-regulated kinase pathway in a rat model of focal cerebral ischemia injury

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.

Comparison of the anti-apoptotic effects of 15-and 35-minute suspended moxibustion after focal cerebral ischemia/reperfusion injury

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.