小牛血清去蛋白注射液对脑细胞缺血缺氧的保护作用及临床应用

小牛血清去蛋白注射液的主要成分是小分子激活肽和磷酸肌醇寡糖,临床上用于治疗缺血性脑血管病。其能保护大脑神经细胞,减轻脑缺血再灌注损伤,改善脑供氧和能量供应,有消除氧自由基、促进神经细胞修复等作用。

脑细胞缺血离体模型——缺血突触体模型的建立与评价

目的 :建立一种脑细胞缺血离体模型。方法 :大鼠脑突触体分别在不同条件下培养 ,电镜观察形态结构 ,测定其生物活性。结果 :突触体结构正常 ,内含线粒体与递质囊泡 ,缺血培养对形态结构无明显影响。突触体悬液与上清液LDH活性的比值在正常和缺血培养条件没有明显差异 ,而缺血培养可使突触体内游离钙浓度显著升高 (P <0 0 5) ,高钾刺激可使其进一步增高 (P <0 0 1 )。结论 :大鼠脑突触体经体外缺血培养后 。

丁苯酞治疗60例进展性脑梗死疗效观察

急性脑梗死属于神经内科急症,发病率与致残率高,目前特效治疗方法少。丁苯酞为国家一类新药,对急性缺血性脑卒中患者中枢神经功能的损伤有改善作用,可促进患者神经功能缺损的改善。2014年6月至2016年6月,我院神经内科应用丁苯酞治疗急性进展性脑梗死患者60例,取得了较好的治疗效果。报告如下。

颈动脉内膜剥脱术12例临床观察

脑梗死发病率高、死亡率高、致残率高。供脑血管任何一段因粥样硬化使管腔狭窄都可以引起脑细胞缺血或坏死。颈内动脉和颈外动脉的分叉处由于血流的冲击容易形成粥样硬化斑块从而使管腔狭窄。粥样硬化斑块一方面可以脱落引起颅内血管的阻塞，另一方面还可以继续增大阻塞颈内动脉而引起脑梗死。颈动脉内膜剥脱术是将粥样硬化斑块和血管内膜一同切除，从而畅通了血管，增加了脑血流，预防了脑梗死的发生。

产后大出血诱发癫痫大发作1例的抢救与护理

癫痫是一种突然发生短暂大脑功能失调的疾病。产后出血诱发癫痫发作在临床上较为少见,其治疗的关键在于控制发作及预防发作,以保患者生命安全。1996年,我科收治了1例,现将急救及护理体会报道如下。1 病例介绍 患者,27岁,G1P0A0L0,于1996年3月17日,以40（5/7）周妊娠,轻度贫血入院。入院后,于3月18日上午8时因NST无反应,给0.5％催产素引产,引产顺利,于下午6时25分平产分娩一女婴,

N-methyl-D-aspartate receptors mediate diphosphorylation of extracellular signal-regulated kinases through Src family tyrosine kinases and Ca^2＋/calmodulin-dependent protein kinase Ⅱ in rat hippocampus after cerebral ischemia

Objective： Extracellular signal-regulated kinases （ERKs） can be activated by calcium signals. In this study, we investigated whether calcium-dependent kinases were involved in ERKs cascade activation after global cerebral ischemia. Methods Cerebral ischemia was induced by four-vessel occlusion, and the calcium-dependent proteins were detected by immunoblot. Results Lethal-simulated ischemia significantly resulted in ERKs activation in N-methyl-D-aspartate （NMDA） receptor-dependent manner, accompanying with differential upregulation of Src kinase and Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） activities. With the inhibition of Src family tyrosine kinases or CaMKⅡ by administration of PP2 or KN62, the phosphorylation of ERKs was impaired dramatically during post-ischemia recovery. However, ischemic challenge also repressed ERKs activity when Src kinase was excessively activated. Conclusions Src family tyrosine kinases and CaMKⅡ might be involved in the activation of ERKs mediated by NMDA receptor in response to acute ischemic stimuli in vivo, but the intense activation of Src kinase resulted from ischemia may play a reverse role in the ERKs cascade.

EFFECT OF ACUPUNCTURE ON NEURONAL APOPTOSIS AFTER FOCAL CEREBRAL ISCHEMIC REPERFUSION INJURY IN RATS

Objective To observe the impacts of acupuncture on cell-cycl ODK4） and neuronal death in hippocampal neurons in rats with focal cerebra e-related factors （cyclin D1, schemic reperfusion injury Methods Middle cerebral artery occlusion （MCAO） was used to establish the model of cerebral ischemic reperfusion injury. Western blot （WB） and flow cytometry （FCM） were applied to the tests of cell-cycle-related factors and apoptosis respectively. Results In 48 h of reperfusion, the expressions of cell-cycle-related factors （cyclin D1, CDK4） in hippocampal neurons and apoptosis were increased. In acupuncture group, the expressions of cyclin DI and CDK4 and apoptosis were reduced remarkably （P 〈 0.01 ）. Conclusion Acupuncture plays the protective role in cerebral ischemic reperfusion injury, which is contributed probably to the modulation of cell-cycle-related factors to inhibit apoptosis.

千万别把中风当春困

春天容易犯困是因为春天湿气逐渐加重,易耗气伤津,这很容易让人感觉困倦。但一些人常将中风的一些前期症状误以为是犯春困,没有重视,从而影响了早期治疗。据临床资料统计,70%以上中风者在发病前5~10天会频繁打呵欠,尤其是老人。

Anti-apoptotic effects of aspirin following cerebral ischemia-reperfusion injury in rats

BACKGROUND： The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE： To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral iscbemia-reperfusion injury （CIRI） in rats. DESING, TIME AND SETTING： A randomized, controlled, animal experiment, performed at the School of Medicine and Pharmaceutics, Jiangnan University between June and October 2006. MATERIALS： Twenty-six male, adult, Sprague Dawley rats （grade Ⅱ）, weighing 240-290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. Aspirin was provided by Sigma （USA）. METHODS： The rats were randomly divided into four groups： sham-operation （SO）, CIRI ＋ vehicle, CIRI ＋ aspirin （6 mg/kg）, and CIRI ＋ aspirin （60 mg/kg）. Rats in the lesion groups were intragastrically administrated saline, aspirin （6 mg/kg）, or aspirin （60 mg/kg）, respectively. MAIN OUTCOME MEASURES： The number of pyramidal neurons with normal appearance in the cerebral cortex at 24 mm from the midline; apoptotic cell death as measured by TUNEL; Bcl-2 and Bax protein localization was determined by immunohistochemistry; malondialdehyde （MDA） and super oxidation （SOD） content were determined by biochemistry method; adenosine triphosphate （ATP） content measured by capillary electrophoresis. RESULTS： Following CIRI, the following parameters were altered compared with sham-operated animals： the number of neurons with normal appearance was significantly reduced in the cerebral cortex; the number of apoptotic cells increased; Bax protein expression was enhanced; and the ratio between Bcl-2 and Bax decreased. In addition, MDA content increased significantly, whereas ATP content decreased （P 〈 0.01）. Aspirin ameliorated the loss of healthy pyramidal neurons. Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax, with no significant difference between the treatment groups. In addition, 60 mg/kg aspirin decreased MDA content and increased ATP levels. However, 6 mg/kg aspirin did not have the same effect. CONCLUSION： Aspirin reduced the number of apoptotic cells following CIRI. These results suggest that the neuroprotective mechanism of aspirin could be related to elevated Bcl-2 protein levels or decreased Bax protein expression. The increase in the ratio of Bcl-2 to Bax appears to be a common anti-apoptotic mechanism of aspirin.

Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

Objective： To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods： lschemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons （CGNs） by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation （OGD）. Results： The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential （its maximal protection ratio was 73.26%） and release of cytochrome c （its maximal inhibition ratio was 42.52%） and the subsequent activation of caspase-3 （its maximal protection ratio was 59.32%） in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion： Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfiusion.

Effects of Electroacupuncture at the Conception Vessel on Proliferation and Differentiation of Nerve Stem Cells in the Inferior Zone of the Lateral Ventricle in Cerebral Ischemia Rats

Objective： To observe the effects of electroacupuncture （EA） at the Conception Vessel on proliferation and differentiation of the nerve stem cells in the inferior zone of the lateral ventricle in cerebral ischemia rats. Methods： The model rats were prepared by occlusion of the middle cerebral artery for 2 hours and then by reperfusion. They were randomly divided into two groups： a control group and an EA group. Changes in differentiation and proliferation of the nerve stem cells were observed 7, 14 and 28 days after successful modeling. Results： As compared with the 7-day control group （C-7d group）, there was no significant difference （P〉0.05） in the numbers of 5-bromodeoxyuridine （Brdu） positive cells, Brdu/GFAP, Brdu/Nestin and Brdu/Nse double-labeled cells in the inferior zone of the lateral ventricle in the EA group 7 days after modeling. However, in the 14-day EA group （R-14d group） and the 28-day EA group （R-28d group）, the numbers of Brdu positive cells and Brdu/GFAE Brdu/Nestin, Brdu/Nse double-labeled cells significantly increased as compared respectively with the 14-day control （C-14d group） and the 28-day control （C-28d） group （P〈0.05 or P〈0.01）. Conclusions： EA at the Conception Vessel promotes differentiation and proliferation of the nerve stem cells in the inferior zone of the lateral ventricle in the cerebral ischemia rats, and may stimulate differentiation of the proliferous nerve stem cells towards the astrocvtes.

Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits

The study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 μg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 μg/(kg&middoth) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-a was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-a and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities.

EFFECT OF DESTRUCTION OF NTS AND PVN ON NEIGUAN (PC6)- ELECTROACUPUNCTURE-I NDUCED IMPROVEMENT OF ISCHEMIC MYOCARDIAL CELLULAR MEMBRANE POTENTIALS IN RABBITS

Objective: To observe the influence of electrolytic destruction of nucleus soli tary tract (NTS) and hypothalamic paraventricular nucleus (PVN) on the effect of electroacupuncture (EA) in improving ischemic myocardia cellular transmembrane action potential (TMAP). Methods: 38 Japanese breed big-ear wh ite rabbits (ane sthetized with 20% Urethane, 4 mL/kg) were randomly divided into acute myocardia l ischemia (AMI) group (n=8), PVN destruction group ( n=12) and PVN+NTS destructio n group (n=18). AMI model was established by occlusion of the descending anterio r branch (DAB) of the coronary artery. TMAP of myocytes was recorded by using a glass microelectrode which was fixed to a suspending spring silver wire. Bilater al "Neiguan"(PC 6) in all the 3 groups were punctured and stimulated electri call y by using parameters of continuous waves, frequency of 7 Hz, intensity of 6 mA a nd duration of 30 minutes. Results: After AMI, ECG-ST elevated significantly whil e APA lowered, APD50 and APD90 shortened clearly in comparison with those of pre -AMI in the 3 groups. Compared with AMI group, ECG-ST values of PVN destructi on group and PVN+NTS destruction group were significantly higher (P <0.05～0.01), whi le APA, APD50 and APD90 all significantly lower in all the recording time course s(P<0.05). The facts displayed that electrolytic destru ction of PVN and PVN+NT S could produce ischemic myocardial injury and reduce the protective effect of E A on ischemic myocardial cells. Comparison between PVN destruction and PVN+NTS g roups showed that all the 4 indexes of the later group were evidently worse than those of the former group (P<0.05), suggesting after des truction of these two n uclei, the effect of EA was worsened further. Conclusion: Electrolytic destru ction of PVN and NTS weakens the protective effect of EA on ischemic myocardial cells, both NTS and PVN take part in the effect of EA of "Neiguan"(PC 6) Point i n improving ischemic myocardium.

Single-strand DNA damages and its relationship with morphological change of neurons at early stage of rat cerebral ischemia/reperf usion

Objective：To discuss the DNA-strand breaks at early stage of middle cerebral artery occlusion/reperfusion (MCAO/R). Methods: Neurons number and morphologic change were observed by Nissl stain method, and DNA strand breaks were in situ detected by using DNA polymerase- I Klenow fragment-mediat-ed nick end-labelling method (Klenow method). Results: Six hours after reperfusion, a few neurons in dam-aged regions appeared morphologic changes while a few Klenow-positive cells were detected (P<0. 01). Twenty-four hours after reperfusion lots of neurons showed morphologic change while the number of Klenow-positive cells immediately and remarkably increased (P<0. 01). Seventy-two hours after reperfusion the number of neurons decreased significantly and the number of Klenow-positive cells was also less than that in 24 h (P<0. 05). Conclusion: ① 24 h after reperfusion when the number of Klenow-positive cells reached peak value, DNA single-strand breaks (SSBs) took place in many Klenow-positive cells, and presumed that DNA SSBs might be an important step in DNA-damage procession which might be induced by free radicals. ② At the same time when lots of DNA SSBs were produced, many neurons in the damaged regions showed morphological change, which indicated that lots of neurons had already progressed to irreversible damages when DNA SSBs took place.

总打哈欠是大脑在呼救

经常熬夜、睡眠差、精神不佳等情况下都会打哈欠,但如果经常打哈欠就该注意了,也许不仅是困,还可能是一些疾病的表现。脑血管疾病脑出血、脑梗死可能引起脑细胞缺血缺氧,表现为脑功能受损,出现偏瘫、偏身感觉障碍、失语、偏盲等临床特征,还可出现频繁打哈欠。睡眠呼吸暂停综合征表现有夜间睡眠打鼾伴呼吸暂停,白天嗜睡、频繁打哈欠。

尼莫地平治疗脑梗塞体感诱发电(SEP)的动态观察(摘要)

尼莫地平治疗脑血管病效果满意已引起人们的关注。本文以 SEP 为检查技术对36例脑梗塞患者应用尼莫地平并与14例丹参治疗组为对照观察其用药前后大脑皮层功能改变情况,从电生理角度客观的评价尼莫地平在治疗脑梗塞,促进神经系统功能恢复上的作用。50例患者男35例,女15例。年龄39～76岁。

Effects of Buyang Huanwu Tang Combined with Bone Marrow Mesenchymal Stem Cell Transplantation on the Expression of VEGF and Ki-67 in the Brain Tissue of the Cerebral Ischemia-Reperfusion Model Rat

Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.

DGMI alleviates OGD/R-induced cell injury by regulating inflammatory and apoptosis signaling pathways

Diterpene ginkgolides meglumine injection(DGMI),a kind of Ginkgo biloba special extract injection,is now used for the treatment of ischemic stroke in convalescence.In the present study,we aimed to confirm whether DGMI could suppress inflammatory responses and apoptosis and explore the potential mechanisms underlying these effects.Cell viability and lactate dehydrogenase(LDH)release were measured by MTS and LDH assays after the cells were exposed to oxygen-glucose deprivation/reoxygenation(OGD/R).The extent of anti-apoptotic effect of DGMI was detected by flow cytometry using Annexin V-FITC/PI double staining assay kit.Pro-inflammatory cytokines,including TNF-α,IL-1β,IL-6 and IL-10,were quantified by a specific Bio-Plex ProTM Reagent Kit.Additionally,activities of TLR2/4,NF-κB p65,MAPK pathway and apoptosis-related proteins as well as cellular localization of NF-κB p65 were determined by Western blotting analysis and immunofluorescence staining,respectively.DGMI at 50μg/mL significantly increased the cell viability and decreased the secretion of IL-1β,IL-6,IL-10 and TNF-αin OGD/R-induced BV2 microglia cells.These effects were also confirmed by LDH assay and Annexin V-FITC/PI staining.Meanwhile,DGMI not only inhibited the protein expressions of TLR2,TLR4,MyD88,p-TAK1,p-IkBα,p-IKKβand Bak,but also decreased the cleaved caspase-3/caspase-3,Bax/Bcl-2 and cleaved PARP-1/PARP-1 ratio in OGD/R-induced BV2 microglia cells.Furthermore,OGD/R-enhanced p-JNK1/2 and p-p38 MAPK expressions and nuclear translocation of NF-κB p65 were also partially inhibited by DGMI.The present study showed that inflammatory responses were triggered in BV2 microglia cells activated by OGD/R,leading to the release of pro-inflammatory cytokines and apoptosis.DGMI suppressed the inflammatory response and apoptosis by regulating the TLR/MyD88/NF-κB signaling pathways and down-regulation of p-JNK1/2 and p-p38 MAPK activation.

Effects of acupuncture plus mild hypothermia on apoptosis-related factors in rats with cerebral ischemia-reperfusion

Objective： To investigate the effect of acupuncture plus mild hypothermia on neurological function impairment score, cerebral infarct size and apoptosis-related factors in cerebral ischemia reperfusion injury（CIRI） rats. Methods： Sixty healthy male Sprague-Dawley（SD） rats were routinely reared for 1 week. Ten rats were randomly selected as the sham operation group and 10 rats as the blank control group, while the remaining 40 rats were subjected to preparing the middle cerebral artery occlusion（MCAO） model by modified filament occlusion method. The 40 MCAO rats were further randomly divided into a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group, with 10 rats in each group. Rats in the sham operation group, the blank control group and the model group did not accept treatment except binding; rats in the acupuncture group received acupuncture treatment; rats in the mild hypothermia group received mild hypothermia treatment; rats in the acupuncture plus mild hypothermia group received acupuncture and mild hypothermia treatment. 72 h after the treatment, neurological function impairment score was performed; the infarct area ratio was determined by 2,3,5-tripheyl tetrazolium chloride（TTC） staining; apoptosis of brain cells was observed by TUNEL method; the expressions of Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry.Results： Compared with the blank control group and the sham operation group, the neurological function impairment score, cerebral infarct area ratio, apoptosis, and the expressions of Bax and Caspase-3 in the model group were significantly increased, while the expression of Bcl-2 was significantly decreased, and there were significant between-group differences（all P〈0.05）. After the treatment, there were statistically significant differences among the treatment groups in the neurological function impairment score, cerebral infarct area ratio and apoptosis in the ischemic side of rats, as well as the expressions of Bcl-2, Bax and Caspase-3（all P〈0.05）, and from the figures, tables and statistical analysis, it was found that a better tendency in the acupuncture plus mild hypothermia group than the acupuncture group or mild hypothermia group. Conclusion： Acupuncture plus mild hypothermia can protect the brain cells by improving neurological function impairment, decreasing cerebral infarct area ratio, reducing the number of apoptotic cells in the ischemic area and regulating the expressions of apoptosis related proteins to inhibit apoptosis.