Cerebral ischemia and neuroregeneration

Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics （i.e., tissue plasminogen activator） and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies again st stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism（s） underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies （i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells） as it relates to cerebral ischemia.

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.

12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the fluorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These findings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

Exogenous neural stem cell transplantation for cerebral ischemia

Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiveness is narrow.Therefore,the incidence of paralysis,hypoesthesia,aphasia,dysphagia,and cognitive impairment caused by cerebral ischemia is high.Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction.Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue.Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years.This review discusses the treatment of ischemic stroke with neural stem cells,as well as the mechanisms of their involvement in stroke treatment.

Therapeutic potential of bone marrow-derived mononuclear cells for experimental cerebral ischemia in mice

Bone marrow mononuclear cells （BMMCs） can be directly harvested from the donor, allowing for easier application compared with bone marrow mesenchymal stem cells. The present study hypothesized that BMMC transplantation could ameliorate cerebral ischemia in a mouse model. BMMCs were double-labeled with PKH26 and 4＇, 6-diamidino-2-phenylindole （DAPI）, followed by infusion into mice via the tail vein to induce focal cerebral ischemia. At 14 days after transplantation, morphological and neurofunctional recovery were analyzed. PKH26 and DAPI double-positive BMMCs were detected in the cerebral hemisphere of all transplantation mice. Following BMMC administration, there was significant difference in neurofunctional recovery, but no significant difference in survival rates between BMMC-treated mice and other mice. These results demonstrate that transplanted BMMCs migrate to brain tissue and promote neurological function recovery in a mouse model of cerebral ischemia.

Electroacupuncture effect on synaptic ultrastructure in focal cerebral ischemia marginal zone of the rat

BACKGROUND：Synapses undergo high levels of plasticity within the nervous system, and cerebral ischemia induces synaptic plasticity changes.OBJECTIVE：To demonstrate the effects of electroacupuncture on ultrastructural synaptic changes in the focal cerebral ischemia marginal zone in rats using quantitative analysis of stereological measurement.DESIGN, TIME AND SETTING：A randomized, controlled, animal experiment was performed at the Experimental Animal Center and Laboratory of Electron Microscopy, Guangzhou University of Traditional Chinese Medicine from January 2008 to January 2009.MATERIALS：The G-6805 electric acupuncture apparatus was provided by Shanghai Huayi Instrument Factory, China.METHODS：A total of 90 male, Wistar rats were randomly assigned to sham-surgery, model, and electroacupuncture groups, with 30 animals in each group. Each group was subdivided into 1 hour, as well as 1, 3, 7, and 21 days post-surgery groups, with six animals assigned to each time point. Heat coagulation-induced occlusion of the middle cerebral artery was performed to establish a model of focal cerebral ischemia. Electroacupuncture was applied immediately following surgery to the electroacupuncture group [4/20 Hz, 2.0-3.0 V, 1-3 mA, to Baihui （GV 20） and Dazhui （GV 14）] for 30 minutes. Treatment was performed once a day, and experimental animals were sacrificed, at 1 hour, as well as 1, 3, 7 and 21 days post-surgery.MAIN OUTCOME MEASURES：At different time points after intervention, changes in synaptic ultrastructure, such as postsynaptic density thickness, synaptic cleft width, and synaptic interface curvature, were observed in the focal cerebral ischemia marginal zone in rats through the use of transmission electronic microscopy.RESULTS：Broken synapses were observed following cerebral ischemia, and the number of synapses was significantly decreased. Compared to the model group, synaptic ultrastructure was significantly improved in the electroacupuncture group. Compared to the sham-surgery group, postsynaptic density thickness was significantly decreased, as were synaptic cleft width and synaptic interface curvature in the electroacupuncture and model groups. However, compared to the model group, postsynaptic density thickness was significantly increased in the electroacupuncture group at the same time point post-surgery （P 〈 0.05 or P 〈 0.01）. In addition, synaptic cleft width and synaptic interface curvature were significantly increased with the passage of time （P〈 0.05 or P〈 0.01）.CONCLUSION：Electroacupuncture significantly ameliorated structural synapse lesion during the early stage of cerebral ischemic injury, promoted repair of synaptic structure, improved structural parameters of synapses, and increased synaptic structural plasticity, which suggested that the therapeutic effect of electroacupuncture was related to synaptic reorganization.

Neuronal differentiation of adipose-derived stem cells and their transplantation for cerebral ischemia

OBJECTIVE： To review published data on the biological characteristics, differentiation and applications of adipose-derived stem cells in ischemic diseases. DATA RETRIEVAL： A computer-based online search of reports published from January 2005 to June 2012 related to the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia was performed in Web of Science using the key words ＂adipose-derived stem cells＂, ＂neural-like cells＂, ＂transplantation＂, ＂stroke＂, and ＂cerebral ischemia＂. SELECTION CRITERIA： The documents associated with the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia were selected, and those published in the last 3-5 years or in authoritative journals were preferred in the same field. Totally 89 articles were obtained in the initial retrieval, of which 53 were chosen based on the inclusion criteria. MAIN OUTCOME MEASURES： Biological characteristics and induced differentiation of adipose-derived stem cells and cell transplantation for disease treatment as well as the underlying mechanism of clinical application. RESULTS： The advantages of adipose-derived stem cells include their ease of procurement, wide availability, rapid expansion, low tumorigenesis, low immunogenicity, and absence of ethical constraints. Preclinical experiments have demonstrated that transplanted adipose-derived stem cells can improve neurological functions, reduce small regions of cerebral infarction, promote angiogenesis, and express neuron-specific markers. The improvement of neurological functions was demonstrated in experiments using different methods and time courses of adipose-derived stem cell transplantation, but the mechanisms remain unclear. CONCLUSION： Further research into the treatment of ischemic disease by adipose-derived stem cell transplantation is needed to determine their mechanism of action.

Effect of adenovirus-mediated gene transfer of Olig1 on oligodendrocyte differentiation and remyelination in a rat model of focal cerebral ischemia

BACKGROUND： The transcription factor Oligl is required for oligodendrocyte maturation and demyelinated lesion repair, and is a key regulator of myelinogenesis following ischemia. OBJECTIVE： To examine the efficacy of intraventricular injection of a recombinant adenovirus-expressing Oligl gene （Ad5-Oligl-eGFP） on oligodendrocyte maturation and myelin repair following focal cerebral ischemia. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Neurology, Beijing Friendship Hospital Affiliated to Capital Medical University from January 2007 to March 2008. MATERIALS： Adenovirus and a recombinant adenovirus containing Oiigl gene （Ad5-Oligl） were provided by Vector Gene Technology, China. METHODS： All 50 rats were induced by middle cerebral artery occlusion. A total of 46 rats were successfully induced and were subsequently randomly assigned to a adenovirus （Ad5） group and recombinant adenovirus-expression Oligl gene （Ad5-Oligl） group, with 23 rats per group. One day after middle cerebral artery occlusion, either Ad5-Oligl-eGFP or Ad5-eGFP （10 μL, 2.3 ×10^11/mL） was injected into the lateral ventricle on the ischemic hemisphere. MAIN OUTCOME MEASURES： Adenovirus-mediated Oligl gene expression in vitro and in vivo was measured by reverse transcription-polymerase chain reaction and immunofluorescence, respectively. Myelin basic protein （MBP） levels were evaluated by Western Blot, immunostaining, and electron microscopy. RESULTS： Exogenous Oligl expression was measured at the periventricular zone of the lateral ventricle 1 day after Ad5-Oligl injection. In the Ad5-Oligl-treated group, MBP protein levels and average intensity of MBP-immunoreactivity （-ir） increased 28 days after middle cerebral artery occlusion, compared with the control group （P 〈 0.01, P 〈 0.05）. Furthermore, myelinated axonal numbers markedly increased following Ad5-Oligl treatment. CONCLUSION： The present data suggested that Ad5-Oligl gene therapy increased MBP expression and the number of remyelinating axons following cerebral ischemia.

Hypertensive-Nimodipine Therapy for Middle Cerebral Artery Vasospasm after Resection of Glioblastoma Multiforme: A Case Report and Literature Review

Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). To our knowledge, this is the first report on DCI after GBM resection. A 52-year-old female patient with headache for one month underwent subtotal resection of a left temporal GBM encasing the proximal middle cerebral artery (MCA). She was well during the immediate postoperative period but developed right upper limb dense monoparesis on postoperative day four with computed tomographic angiography confirming left MCA vasospasm. Symptoms were significantly alleviated with weeklong hypertensive therapy and nimodipine administration;however they recurred soon after cessation of treatment. A high index of clinical suspicion is needed for the diagnosis of post-tumor resection DCI. Any new postoperative neurological deficit that cannot be explained by hemorrhage, seizures or infection should be expeditiously investigated by angiography or transcranial Doppler sonography. Prompt initiation of hypertensive and nimodipine therapy can possibly reverse neurological deficit. Treatment should be guided by Doppler, angiographic or perfusion imaging studies and not by clinical improvement alone.

~1H-magnetic resonance spectroscopy screening for animals with acute cerebral infraction suitable forthrombolytic therapy

BACKGROUND： As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy （1H-MRS） may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke. OBJECTIVE： To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability. DESIGN： Randomly controlled animal study. SETTINGS： Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom ＆ Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science. MATERIALS： Eleven healthy adult Sprague-Dawley （SD） rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK （e） 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. METHODS： The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom ＆ Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group （n =6） and 60-minute self-thrombo-embolism group （n =5）. Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid （NAA）/phosphocreatine （PCr） ＋ creatine （Cr）, choline phosphate （Cho）/PCr＋Cr and lactic acid （Lac）/PCr＋Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope. MAIN OUTCOME MEASURES： ① Metabolic changes of NAA/PCr＋Cr, Cho/PCr＋Cr and Lac/PCr＋Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue. RESULTS： Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests ： In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy （0.252±0.01, 0.603±0.01, P 〈 0.01）. Lac/（PCr＋Cr） ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis （P 〈 0.01）. The NAA/ （PCr＋Cr） ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis （0.922±0.16, 1.196±0.01, P 〈 0.05）. In 60-minute self-thrombo-embolism group, the Lac/（PCr＋Cr） ratio was higher at 3 hours after thrombolysis than that before thrombolysis （0.846±0.12, 0.601±0.11, P 〈 0.05） and the NAA/（PCr＋Cr） decreased at 3 hours after the embolism. Fluctuation of NAA/ （PCr＋Cr） ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image： T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA 〉 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations： Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateralpart of corpus striatum. CONCLUSION： ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy.

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/GFAP, 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 astrocytes.

New Developments in Drug Therapy and Research of Cerebral Vasospasm

In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.

INFLUENCE OF DIFFERENT NEEDLE-RETAINING DURATION ON CEREBRAL HEMODYNAMICS OF CEREBRAL PARALYSIS CHILDREN

Objective: To investigate the effects of different needle-retaining duration on cerebral hemodynamics in cerebral paralysis (CP) children. Methods: A total of 20 cases of CP children were subjected into this study. Changes of systolic peak value (Vs), blood flow velocity at the end-diastolic phase (Ved), mean velocity (Vm), pulsation index (PI) and resistance index (RI) of the cerebral hemodynamics before and after performing JIN’s Three-Needling Therapy with the needles retained for 30 min (group A) and 5 min (group B) were observed by using transcranial Doppler ultrasonography (TCD). Results: After acupuncture, the blood flow in the middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA) was accelerated, and the resistance of blood vessels decreased. The effect of needle-retaining-30 min was better than that of needle-retaining-5 min. Conclusion: In treating cerebral paralysis by using JIN’s Three-Needling Therapy, sufficient stimulation provided by needle remaining is an important factor for achieving satisfactory therapeutic effects.

从铁死亡途径分析针刺对脑缺血再灌注损伤大鼠脑保护的作用机制

目的观察醒脑开窍针刺法对脑缺血再灌注损伤大鼠神经功能和脑组织病理形态学的影响,检测脑缺血再灌注组织内谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、转铁蛋白受体(transferrin receptor,TfR)和膜铁转运蛋白1(ferroportin 1,Fpn1)含量变化,从铁死亡途径探讨针刺对脑缺血再灌注大鼠的脑保护机制。方法25只清洁级雄性Wistar大鼠随机分为假手术组5只、模型组10只、电针组10只。后两组分别再按针刺干预时间分为24 h、72 h两个亚组,每组5只。采用改进的Zea Longa线栓法制作大脑中动脉缺血再灌注模型。电针组予针刺内关、水沟、三阴交,留针期间患侧内关、三阴交穴连接神经穴位刺激仪。采用Zausinger六分法评定神经功能缺损程度,尼氏染色法观察脑组织病理形态改变,酶联免疫吸附测定法对比各组大鼠GSH、MDA、TfR、Fpn1、GPX4的含量。结果与假手术组比较,造模后模型组及电针组神经功能评分均降低(P<0.01)。与模型组比较,电针干预24 h后神经功能评分升高,72 h后评分进一步升高(P<0.01)。造模24 h后,模型组及电针组尼氏小体数量减少,颜色变浅;72 h后模型组尼氏小体更少,电针组尼氏小体数量有一定的恢复。与假手术组比较,模型组MDA、TfR、Fpn1升高、GSH及GPX4降低(P<0.01)。与模型组比较,电针干预24 h及72 h时后MDA、TfR降低、GSH、GPX4及Fpn1升高(P<0.01,P<0.05)。与针刺24 h对比,针刺72 h后MDA、TfR降低更明显,GSH及Fpn1升高更明显(P<0.01,P<0.05)。结论铁死亡是脑缺血再灌注损伤中细胞死亡的重要方式之一,醒脑开窍针刺法可调节脑缺血再灌注大鼠脑组织铁代谢,提高细胞抗氧化能力,抑制神经细胞铁死亡,其脑保护作用与铁死亡途径密切相关。

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

颈椎横突尖电项针法调控后循环缺血大鼠血管和神经新生

[目的]观察颈椎横突尖电项针法对后循环缺血大鼠脑血流量和血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、内皮抑素(endostatin,ES)和神经巢蛋白(Nestin)、神经元特异性核蛋白(NeuN)蛋白表达的影响,探讨颈椎横突尖电项针法对后循环缺血大鼠血管新生和神经再生的作用及具体机制。[方法]32只雄性SD大鼠结扎右侧颈总动脉和右锁骨下动脉,复制成永久性后循环缺血模型,假手术组8只仅暴露血管不结扎。将造模成功的24只大鼠分为模型组、西药组和颈椎横突尖电项针组,每组8只。模型组不予任何针刺治疗,但在颈椎横突尖电项针组进行针刺治疗的相同时间内,对该组大鼠进行抓取、捆绑和固定,确保时间、条件与颈椎横突尖电项针组相同;颈椎横突尖电项针组大鼠双侧风池穴和C2、C4、C6颈椎尖位置予以电针治疗;西药组采用尼莫地平溶液灌胃。治疗频率每天一次,连续治疗6 d为1个疗程,1个疗程结束后休息1 d,共2个疗程。采用超声多普勒血流仪检测各组大鼠平均脑血流量,异硫氰酸荧光素-葡聚糖示踪法检测缺血区大脑皮质新生毛细血管数量,苏木精-伊红(hematoxylin-eosin,HE)染色法观察缺血区大脑皮质组织形态,免疫荧光染色检测右侧大脑纹状体中Nestin、NeuN的阳性表达,免疫印迹分析血管新生相关因子VEGF、bFGF、MMP-9、ES蛋白表达水平。[结果]与假手术组比较,干预后模型组大鼠脑血流量显著降低(P<0.01),新生毛细血管数量增加(P<0.05),右侧纹状体Nestin、NeuN阳性表达增加(P<0.05,P<0.01),缺血区大脑皮质VEGF、MMP-9、bFGF、ES蛋白表达增加(P<0.01,P<0.05)。与模型组比较,西药组和颈椎横突尖电项针组大鼠脑血流量明显上升(P<0.01),缺血区大脑皮质新生毛细血管数量增加(P<0.05),右侧纹状体Nestin、NeuN阳性表达增加(P<0.05,P<0.01),缺血区大脑皮质VEGF、bFGF蛋白表达增加(P<0.05),MMP-9、ES蛋白表达减少(P<0.01)。与西药组比较,颈椎横突尖电项针组大鼠右侧纹状体Nestin、NeuN阳性表达增加(P<0.05),其余指标差异均无统计学意义(P>0.05)。[结论]颈椎横突尖电项针法可改善后循环缺血大鼠脑血流量,减轻神经缺损程度,促进大鼠血管和神经发生,其作用可能与调控血管新生相关因子的蛋白表达有关。

右美托咪定对神经介入脑缺血-再灌注损伤的保护作用观察

探讨右美托咪定应用于脑梗死神经介入治疗对脑缺血-再灌注损伤的保护效果。选取2021年4月—2023年4月贵州中医药大学第一附属医院收治的60例脑梗死经神经介入治疗的患者为研究对象。采用随机数字表法将患者分为两组,分别为参照组和试验组,每组各30例。试验组麻醉诱导前10min应用右美托咪定,参照组应用等容量的0.9%浓度生理盐水。比较两组患者的治疗效果。结果显示,T1、T2、T3、T4阶段,两组患者HR、MAP、ICP指标水平均有一定程度的升高,试验组升高幅度比参照组小(P<0.05);术后7天、14天,试验组NIHSS评分低于参照组,日常生活能力评分高于参照组(P<0.05);治疗后,试验组患者SOD、MDA、NSE、S-100B、TNF-α、IL-6等水平均低于参照组(P<0.05)。研究发现,脑梗死神经介入治疗中,应用右美托咪定能够保护患者的神经功能,减轻其脑缺血-再灌注损伤程度,可提高其日常生活能力。

头穴与项穴丛刺治疗脑供血不足性眩晕TCD即时效应对比研究

目的比较头穴丛刺和项穴丛刺对脑供血不足性眩晕患者脑血流即时效应的影响。方法将57例脑供血不足性眩晕患者随机分成治疗组29例和对照组28例。治疗组采用头穴丛刺治疗,对照组采用项穴丛刺治疗。观察两组治疗前后经颅多普勒(transeranial doppler,TCD)所示大脑中动脉(MCA)、颈内动脉(ICA)、基底动脉(BA)、小脑后下动脉(PINCA)、椎动脉(VA)的收缩期血流速度(Vs)、舒张期血流速度(Vd)、平均血流速度(Vm)变化。结果治疗组治疗后各血管(MCA、ICA、BA、PINCA、VA)血流速度(Vs、Vd、Vm)与同组治疗前比较,差异均具有统计学意义(P<0.01,P<0.05)。对照组治疗后MCA、ICA、VA及PINCA血流速度与同组治疗前比较,差异均具有统计学意义(P<0.01)。对照组治疗后BA的Vs与Vm与同组治疗前比较,差异均具有统计学意义(P<0.05)。治疗组治疗后各血管血流速度与对照组比较,差异均无统计学意义(P>0.05)。结论头穴丛刺和项穴丛刺均能即时改善患者大脑各低流速血管的Vs、Vd、Vm,两种刺法对各血管Vs、Vd、Vm改善程度相近。

OBSERVATION OF THE EFFECTS OF ZHENXUANYIN ON CBF OF RATS WITH VERTEBROARTERIAL ISCHEMIA AND CBF OF HEALTHY RATS

In order to observe the improvement effects of Zhenxuanyin (ZXY) to the rats vertebral artery infarction, it's prevention ability to the Pulsinelli's 4 vessel occlusion (4VO) rats model and it's influences to the normal rats brain. The infarction of the rats vertebral artery (vertebral 2 VO) and the 4VO rats model were achieved through electrocoagulation. 123 I IMP was used to trace cerebral blood flow (CBF). Except of cerebral cortex, the blood flow of each region decreased. Dosage of ZXY at 0 3 g/kg was able to normalize the decreased blood flows in cerebral regions. Healthy rats were medicated at a daily 0 3 g/kg and 1 g/kg dosage of ZXY. At the end of 1 week, they were made into 4VO model rats. No effective prevention effect was found. ZXY had no obvious effect on the CBF of normal rats. Vertebral 2 vessel occlusion is similar to clinical mild cerebral inefficient blood supply, therefore closer to the model of clinical VID. ZXY is able to normalize this incomplete compensation state, which is consistent with the curative effect on Pulsinelli's 4VO model rats. The best curative dosage of ZXY does not improve normal rats' CBF implied that ZXY used to cure regional cerebral ischemia at the acute stage does not dilate the cerebral blood vessel in the normal region, thus does not cause blood stealing in the brain 〔5〕 , Therefore, ZXY is an ideal CBF improving agent.

基于PERK-eIF2α信号通路探讨眼针对脑缺血再灌注损伤大鼠脑组织Atg12表达的影响

目的 通过检测各组脑组织中磷酸化蛋白激酶R样内质网激酶(phosphorylation protein kinase-like ER kinase, p-PERK)、磷酸化真核起始因子2α(phosphorylated α subunit of eukaryotic initiation factor 2,p-eIF2α)、自噬相关基因12(antigen, Atg12)蛋白表达水平的变化,探讨眼针是否能够通过调控内质网应激信号通路PERK-eIF2α影响脑缺血再灌注损伤(cerebral ischemia reperfusion injury, CIRI)大鼠脑组织Atg12的表达。方法 建立大鼠脑缺血再灌注损伤模型,实验分为4组,即:对照组、假手术组、模型组、眼针组。末次针刺后,对各组大鼠进行神经功能缺损评分,透射电镜观察各组大鼠自噬小体的表达情况,然后采用Western blot法检测脑组织中p-PERK、p-eIF2α、Atg12蛋白表达。结果 与对照组和假手术组相比,模型组大鼠神经功能缺损评分、脑组织中p-PERK、p-eIF2α、Atg12蛋白表达均升高,差异具有统计学意义(P<0.01),自噬小体数量增多;与模型组相比,眼针组大鼠神经功能缺损评分、脑缺血组织中p-PERK、p-eIF2α、Atg12的蛋白表达明显降低,差异具有统计学意义(P<0.01),自噬小体数量减少。结论 眼针能够降低脑缺血再灌注损伤模型大鼠脑组织自噬蛋白Atg12的表达,其机制可能与调控内质网应激通路PERK-eIF2α有关。