Neuroprotective effect of cycloheximide on hypoxic-ischemic brain injury in neonatal rats

This study was done to determine the neuroprotective effect of cycloheximide on neonatal hypoxic-ischemic brain injury. Seven day-old newborn rat pups were subjected to 90 min of 8% oxygen following a unilateral carotid artery ligation. The extent of cerebral infarction was evaluated at 1 and 4 week of recovery. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluoresceinated annexin V and propidium iodide. Brain infarction area was significantly increased at 4 week compared to 1 week after hypoxia-ischemia in the control group. With cycloheximide treatment, the number of TUNEL positive cells in the ipsilateral cerebral cortex at 48 hr and peri-infarct area at 1 and 4 week of recovery was significantly reduced, both apoptotic and necrotic cells by flow cytometry 48 hr after the injury were significantly reduced, and the extent of cerebral infarction at 1 and 4 week of recovery was also significantly attenuated compared to the hypoxia-ischemia control group. In summary, our data suggest that apoptosis plays an important role in the development of delayed infarction, and inhibition of apoptosis with cycloheximide significantly reduces the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia.     

Quantitative in Vivo Detection of Brain Cell Death after Hypoxia Ischemia Using the Lipid Peak at 1.3 ppm of Proton Magnetic Resonance Spectroscopy in Neonatal Rats

This study was performed to determine the accuracy of proton magnetic spectroscopy (¹H-MRS) lipid peak as a noninvasive tool for quantitative in vivo detection of brain cell death. Seven day-old Sprague Dawley rats were subjected to 8% oxygen following a unilateral carotid artery ligation. For treatment, cycloheximide was given immediately after hypoxic ischemia (HI). Lipid peak was measured using ¹H-MRS at 24 hr after HI, and then brains were harvested for fluorocytometric analyses with annexin V/propidium iodide (PI) and fluorescent probe JC-1, and for adenosine-5''-triphosphate (ATP) and lactate. Increased lipid peak at 1.3 ppm measured with ¹H-MRS, apoptotic and necrotic cells, and loss of mitochondrial membrane potential (ΔΨ) at 24 hr after HI were significantly improved with cycloheximide treatment. Significantly reduced brain ATP and increased lactate levels observed at 24 hr after HI showed a tendency to improve without statistical significance with cycloheximide treatment. Lipid peak at 1.3 ppm showed significant positive correlation with both apoptotic and necrotic cells and loss of ΔΨ, and negative correlation with normal live cells. Lipid peak at 1.3 ppm measured by ¹H-MRS might be a sensitive and reliable diagnostic tool for quantitative in vivo detection of brain cell death after HI.     

Granulocyte stimulating factor attenuates hypoxic-ischemic brain injury by inhibiting apoptosis in neonatal rats

Purpose

This study was undertaken to determine the neuroprotective effect of granulocyte stimulating factor (G-CSF) on neonatal hypoxic-ischemic brain injury.

Materials and Methods

Seven-day-old male newborn rat pups were subjected to 110 minutes of 8% oxygen following a unilateral carotid artery ligation. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluorescinated annexin V and propidium iodide (PI) and JC-1 (5,5'',6,6''-tetrachloro-1,1'',3,3''-tetraethylbenzimidazolyl-carbocyanine iodide). The extent of cerebral infarction was evaluated at 2 weeks after recovery.

Results

With a single dose (50 µg/ kg) of G-CSF treatment immediately after hypoxic-ischemic insult, hypoxia-ischemia induced increase in TUNEL-positive cells, annexinV+/PI-and JC-1 positive apoptotic cells in the ipsilateral cerebral cortex was significantly reduced at 24 hours, measured by flow cytometry, and the extent of cerebral infarction at 2 weeks after recovery was also significantly attenuated compared to the hypoxia-ischemia control group.

Conclusion

Our data suggest that G-CSF is neuroprotective by inhibiting apoptosis, thereby reducing the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia (HI).     

丁苯酞预处理对缺血再灌注大鼠海马神经元超微结构的影响

目的:探讨丁苯酞预处理对脑缺血再灌注损伤后大鼠海马神经元的保护作用。方法:雄性SD大鼠随机分成5组,假手术组(Sham组),缺血再灌注组(I/R组),丁苯酞低、中、高剂量预处理组。低、中、高剂量组分别于造模前1周给予20、40、80 mg/kg丁苯酞灌胃,每天1次,共7 d。I/R组和Sham组灌服等量生理盐水。改良Zea Longa线栓法制备大鼠右侧大脑中动脉阻断局灶性脑缺血再灌注模型,于再灌注后24 h行Zea Longa评分标准进行神经功能缺损评分;2%氯化三苯基四氮唑(TTC)染色测量梗死体积;H-E染色观察海马神经元的组织病理学变化;透射电镜观察海马神经元的超微结构及病理变化。结果:NBP预处理能明显减少脑梗死体积,改善神经功能学评分,保护线粒体,减轻神经元损伤。结论:丁苯酞预处理具有预防性脑保护作用。     

急性脑缺血损伤大鼠海马神经元谷氨酸转运体的表达

目的：研究急性脑缺血损伤大鼠海马神经元谷氨酸转运体（EAAC1）的表达变化。 方法： 采用EAAC1反义寡核苷酸脑内注射，用插线法建立大鼠局灶性脑缺血模型(MCAO)。运用Western blot法和TTC染色观察缺血区EAAC1表达和梗塞体积；采用RT-PCR 和Western blot法，测定海马EAAC1 mRNA和蛋白在缺血1 h、6 h、24 h的变化。结果： 注射EAAC1反义寡核苷酸组大鼠梗塞体积［(105.67±8.70) mm3］显著小于正义组。缺血1 h大鼠海马EAAC1 mRNA表达（0.963±0.117）与假手术组（0.907±0.113）无明显差异，缺血6h、24h持续高于缺血1 h（分别为1.116±0.104和1.428±0.078）。而海马EAAC1蛋白表达（0.640±0.027）在缺血24 h高于假手术组，缺血1 h和6h EAAC1表达与假手术组比较无显著差异（分别为0.330±0.018、0.330±0.015）。结论： EAAC1可促进缺血脑损伤,在急性脑缺血病理过程中表达增加。     

缺氧缺血脑损伤大鼠脑组织Cofilin 1与ERK1/2蛋白表达与磷酸化的分析

目的探索新生大鼠缺氧缺血脑损伤模型脑组织Cofilin1与ERK1/2蛋白表达与磷酸化及其在脑组织中分布的规律。方法新生7日龄SD大鼠,手术结扎左侧颈总动脉并经低氧处理造成缺氧缺血脑损伤(HIBD)模型,以假手术组为对照,应用western Blot和免疫组化方法检测损伤后一定时间段(0h～48h)损伤侧脑组织Cofilin1与磷酸化cofilin1(p-Cofilin1)及Erk1/2和磷酸化ERK1/2(p-ERK1/2)的表达变化,同时检测其在损伤大鼠脑组织和细胞中的表达和分布。结果 Western blot检测显示,HIBD新生SD大鼠脑组织中Cofilin1在HI后的表达与对照组相比也未见明显改变,但磷酸化Cofilin1在HI后1h～12h之间降低,24h后恢复正常;ERK1/2蛋白在不同时点的表达与对照组相比未见明显差异,但可见磷酸化ERK1/2(p-ERK1/2)在缺氧缺血处理(HI)后0h略低于正常,而在1-2h内迅速升高并高于正常对照和假手术,在2h后又逐渐降低。免疫组化结果显示Cofilin1与p-cofilin1在损伤大鼠脑中主要分布于海马和大脑皮质,尤其p-Cofilin表达分布以海马的颗粒细胞为主,并且在HI后7d-14d表达明显增强,在21d则明显降低。结论 Cofilin和ERK的磷酸化修饰与缺氧缺血脑损伤的发生和发展过程有较密切的关系,且cofilin1和p-cofilin1在大脑海马区的定位分布,提示其可能与大脑的学习记忆功能的损伤与修复有一定的关系。     

Erythropoietin attenuates brain injury, subventricular zone expansion, and sensorimotor deficits in hypoxic-ischemic neonatal rats

The aim of this study was to investigate the effect of erythropoietin (EPO) on histological brain injury, subventricular zone (SVZ) expansion, and sensorimotor function deficits induced by hypoxia-ischemia (HI) in newborn rat pups. Seven-day-old male rat pups were divided into six groups: normoxia control, normoxia EPO, hypoxia control, hypoxia EPO, HI control, and HI EPO group. Sham surgery or HI was performed in all animals. HI was induced by ligation of the right common carotid artery followed by 90 min of hypoxia with 8% oxygen. Recombinant human EPO 3 U/g or saline was administered intraperitoneally, immediately, at 24- and 48-hr after insult. At two weeks after insult, animals were challenged with cylinder-rearing test for evaluating forelimb asymmetry to determine sensorimotor function. All animals were then sacrificed for volumetric analysis of the cerebral hemispheres and the SVZ. The saline-treated HI rats showed marked asymmetry by preferential use of the non-impaired, ipsilateral paw in the cylinder-rearing test. Volumetric analysis of brains revealed significantly decreased preserved ipsilateral hemispheric volume and increased ipsilateral SVZ volume compared with the sham-operated animals. Treatment of EPO significantly improved forelimb asymmetry and preserved ipsilateral hemispheric volume along with decreased expansion of ipsilateral SVZ following HI compared to the saline-treated HI rats. These results support the use of EPO as a candidate drug for treatment of neonatal hypoxic-ischemic brain damage.     

mTOR activates hypoxia-inducible factor-1α and inhibits neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia

The mammalian target of rapamycin (mTOR) exerts neuroprotective effects under hypoxic or ischemic conditions. To explore whether mTOR participates in neuroprotective signaling through regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and neuronal apoptosis in developing rat brain with hypoxia-ischemia (HI), we operated on postnatal day 10 rats by ligating the common carotid artery followed by exposure to systemic hypoxia. Brains were collected at various intervals to detect the expression of mTOR, phosphorylated mTOR (p-mTOR), HIF-1α, VEGF and cleaved caspase 3 (CC3), using immunohistochemistry and Western blot analysis. We also used terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) to detect neuronal apoptosis. The p-mTOR protein expression increased at 2 h after HI, peaked at 8 h, lasted 24 h, and then dropped to the basal level. Also, the expression of HIF-1α and VEGF was significantly enhanced and peaked at 8 h after HI. Up-regulated expression of CC3 was observed at 2 h, peaked at 24 h, and lasted 72 h after HI. Increased neuronal apoptosis is associated with reduced HIF-1α and VEGF expression. Furthermore, pretreatment with rapamycin, a mTOR specific inhibitor, significantly inhibited HIF-1α and VEGF protein after HI. The expression of CC3 and the number of TUNEL-positive cells were up-regulated at 8 h and down-regulated at 24 h after HI in the rapamycin-treated group. Our findings suggest that mTOR may participate in the regulation of HIF-1α, VEGF and neuronal apoptosis, serving neuroprotective functions after HI in developing rat brain.     

Hcy与TpP用于ACI早期诊断的价值

目的：探讨同型半胱氨酸（Hcy）及血栓前体蛋白（TpP）检测在急性脑梗死（ACI）早期诊断中的价值。方法：用ELISA对64例ACI患者,在发病后48h及以内不同时期的血浆Hcy、TpP及D-二聚体（D-D）含量进行检测,并与正常组比较。结果：ACI患者在治疗前血浆TpP、Hcy含量显著高于正常对照组（P〈0.01）,D-D水平在发病后12h呈升高趋势;血浆TpP在发病6h内水平达到高峰,后随发病时间浓度递减;Hcy在监测的48h内一直处于较高水平。结论：血浆TpP、Hcy水平升高是引发脑血栓的重要因素,是ACI早期检测的可靠指标,而D-D水平的升高说明脑梗死患者的继发纤溶亢进,在凝血系统激活的同时,纤溶系统也被激活。同时检测TpP、Hcy对脑梗死疾病的早期诊断及防治有重要价值。     

缺血后处理局灶性脑缺血再灌注模型大鼠相关通路以及白细胞介素8的表达

背景：缺血后处理能够激发内源性保护作用,抑制缺血再灌注后的炎症反应,但具体机制目前尚不明确。目的：观察缺血后处理对局灶性脑缺血再灌注大鼠Toll样受体4-核因子κB信号转导通路以及白细胞介素8表达的影响,进一步阐述缺血后处理的神经保护机制。方法：将110只大鼠随机分为假手术组10只、模型组和缺血后处理组各50只,将大鼠按照Zea-Longa法建立局灶性脑缺血再灌注模型,再进行缺血后处理,即大脑中动脉闭塞2 h后进行3个循环的再灌注15 s/缺血15 s,设模型组和假手术组作对照。对各组进行神经行为学评分,TTC染色测定脑梗死体积,免疫组织化学法检测脑组织Toll样受体4、核因子кB和白细胞介素8蛋白表达,原位杂交法检测其mRNA表达。结果与结论：模型组、缺血后处理组大鼠都出现神经行为学缺失及缺血侧大脑半球梗死。再灌注6,12,24,48,72 h,与模型组相比,缺血后处理组大鼠神经行为学评分显著改善(P < 0.05)、脑梗死体积明显减少(P < 0.05)。模型组和缺血后处理组Toll样受体4、核因子кB、白细胞介素8蛋白和mRNA表达于再灌注6 h时已升高,24 h达峰值。再灌注6,12,24,48,72 h,与模型组各对应时间点亚组比较,缺血后处理组上述各因子表达均显著降低(P < 0.05)。结果证实,缺血后处理可抑制缺血再灌注引起的炎症反应,通过抑制Toll样受体4-核因子κB信号转导通路和下调白细胞介素8的表达,以此发挥神经保护作用。  中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

他米巴罗汀减轻大鼠脑缺血再灌注损伤

目的探讨他米巴罗汀(Am80)对大鼠脑缺血再灌注损伤(CIR)的作用。方法将大鼠随机分为:假手术组(sham)、模型组(I/R)和他米巴罗汀干预组(Am80,灌胃给予Am80 6 mg/kg)。采用线栓法建立大脑中动脉栓塞(MCAO)模型。术后24 h断头取脑,在处死前采用双盲法进行神经行为学评分;TTC染色测定脑梗死体积;Western blot和RT-q PCR法分别检测RARα、Bcl-2和Bax蛋白及mRNA的表达。结果 Am80可显著改善MCAO大鼠神经功能缺损,有效地降低脑梗死体积(P0.01),上调RARα和Bcl-2表达(P0.01),降低Bax的表达(P0.01)。结论他米巴罗汀对脑缺血再灌注损伤大鼠有保护作用,其作用可能与抗凋亡有关。     

A novel calpain inhibitor, ((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice

Cerebral ischemia induces Ca(2+) influx into neuronal cells, and activates several proteases including calpains. Since calpains play important roles in neuronal cell death, calpain inhibitors may have potential as drugs for cerebral infarction. ((1S)-1((((1S)-1-Benzyl-3- cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945) is a novel calpain inhibitor that has good membrane permeability and water solubility. We evaluated the effect of SNJ-1945 on the focal brain ischemia induced by middle cerebral artery occlusion (MCAO) in mice. Brain damage was evaluated by assessing neurological deficits at 24 h or 72 h after MCAO and also by examining 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining of brain sections. When injected at 1 h after MCAO, SNJ-1945 at 30 and 100 mg/kg, i.p. decreased the infarction volume and improved the neurological deficits each assessed at 24 h. SNJ-1945 at 100 mg/kg, i.p. also showed neuroprotective effects at 72 h and reduced the number of TUNEL-positive cells at 24 h. SNJ-1945 was able to prevent neuronal cell death even when it was injected at up to 6 h, but not at 8 h, after MCAO. In addition, SNJ-1945 decreased cleaved alpha-spectrin at 6 h and 12 h, and active caspase-3 at 12 h and 24 h in ischemic brain hemisphere. These findings indicate that SNJ-1945 inhibits the activation of calpain, and offers neuroprotection against the effects of acute cerebral ischemia in mice even when given up to 6 h after MCAO. SNJ-1945 may therefore be a potential drug for stroke.     

氯喹对大鼠脑缺血再灌注自噬相关蛋白的影响

目的　探讨氯喹对大鼠脑缺血再灌注自噬相关蛋白的影响及其机制。 方法　取75只大鼠随机分为假手术组（Sham）,模型组（Model）,氯喹（CQ)20、40、60 mg/kg组,每组15只。应用线栓法使右脑中动脉栓塞（MCAO),栓塞2 h。3个药物组于栓塞后立即腹腔注射CQ 20、40、60 mg/kg,其余各组注射2 ml 0.9%氯化钠。再灌注24 h后,采用神经功能缺损评分、TTC染色判断模型是否制作成功,采用免疫荧光和免疫印迹法检测大鼠脑自噬相关蛋白的表达。 结果 ① Sham组, Model组, CQ 20、40、60 mg/kg组神经功能缺损评分,分别为0、2.67±0.49、2.93±0.26、2.40±0.51及1.93±0.70。通过TTC染色与Model组比较梗死面积,CQ 20 mg/kg组增大,CQ 40 mg/kg组无明显变化,CQ 60 mg/kg组减小。②免疫荧光和免疫印迹结果显示各组均有蛋白(Atg5、Atg7、Beclin1、Atg12）表达,与Model组比较,其中Sham组仅有极少量表达（P<0.05),CQ 20 mg/kg组表达量无明显差异,CQ 60 mg/kg组的表达量明显减少（P<0.05)。 结论　氯喹对大鼠脑缺血再灌注损伤有双重作用,低剂量20 mg/kg加重损伤,高剂量60 mg/kg减轻损伤。其机制可能与某些脑自噬相关蛋白表达的量有关。     

Leptin controls ketone body utilization in hypothalamic neuron

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of severe and permanent neurologic disability after birth. The inducible cyclooxygenase COX-2, which along with COX-1 catalyzes the first committed step in prostaglandin (PG) synthesis, elicits significant brain injury in models of cerebral ischemia; however its downstream PG receptor pathways trigger both toxic and paradoxically protective effects. Here, we investigated the function of PGE₂ E-prostanoid (EP) receptors in the acute outcome of hypoxic-ischemic (HI) injury in the neonatal rat. We determined the temporal and cellular expression patterns of the EP1-4 receptors before and after HIE and tested whether modulation of EP1-4 receptor function could protect against cerebral injury acutely after HIE. All four EP receptors were expressed in forebrain neurons and were induced in endothelial cells after HIE. Inhibition of EP1 signaling with the selective antagonist SC-51089 or co-activation of EP2-4 receptors with the agonist misoprostol significantly reduced HIE cerebral injury 24 h after injury. These receptor ligands also protected brain endothelial cells subjected to oxygen glucose deprivation, suggesting that activation of EP receptor signaling is directly cytoprotective. These data indicate that the G-protein coupled EP receptors may be amenable to pharmacologic targeting in the acute setting of neonatal HIE.     

Hypoxic ischaemic hypothermia promotes neuronal differentiation and inhibits glial differentiation from newly generated cells in the SGZ of the neonatal rat brain

Hypothermia is a potential therapy for cerebral hypoxic ischaemic injury in adults and neonates. The mechanism of the neuroprotective effects of hypothermia after hypoxia-ischaemia (HI) in the developing rat brain remains unclear. In this research, 7-day-old rats underwent left carotid artery ligation followed by the administration of 8% oxygen for 2 h. These rats were divided into hypothermic (rectal temperature, 32-33 °C for 24 h) and normothermic (36-37 °C for 24 h) groups immediately after HI. All rats were given 50 mg/kg/day 5-bromodeoxyuridine (BrdU) intraperitoneally at 4-6 days and sacrificed at 1 or 2 weeks after HI. We found a significant decrease in infarct volume and the neuron loss were also detected in the subgranular zone (SGZ) in the hypothermic group at 7 and 14 days after HI compared with the normothermic group. BrdU immunopositive cells were reduced greatly in the hypothermic group compared with the normothermic group. Hypothermia did not change the number of nestin-labelled cells in the ipsilateral SGZ at 1 and 2 weeks after HI. The differentiation of newly generated cells was assessed by double immunolabelling of BrdU with glial fibrillary acidic protein (GFAP), O4 or Neuronal Nuclei (NeuN). The ratio of BrdU(+)-GFAP(+) or BrdU(+)-O4(+) to total BrdU(+) staining decreased dramatically, but the ratio of BrdU(+)-NeuN(+) to total BrdU(+) staining increased significantly in the hypothermic group compared to the normothermic group at 2 and 6 weeks after HI. These results suggest that the reduction in neuron loss observed after mild hypothermia may be associated with enhanced neuronal differentiation and decreased glial differentiation in the SGZ after HI. These observations are noteworthy for clinical hypothermia therapy following cerebral HI injury during the perinatal period.     

心肌梗死模型家猪存活心肌的磁共振延迟成像评价

背景：心脏磁共振延迟成像被认为是极有前景的无创性判断心肌存活状态的影像检查手段。目前常用的对比剂Gd-DTPA存在过高或过低评价存活心肌和不可逆性梗死心肌,而坏死亲和性对比剂ECIII-600可以准确地反映坏死心肌的面积。 目的：对比冠脉内注射坏死亲和性对比剂在猪再灌注急性心肌梗死存活心肌诊断中的应用价值。 方法：三四个月龄普通家猪12头,建立急性再灌注心肌梗死动物模型,分别冠脉内注射0.1 mmol/kg Gd-DTPA或         0.005 mmol/kg ECIII-600。胸导R波触发心电门控,T1加权FAST序列,短轴面延迟强化扫描成像。扫描结束后沿短轴面将心脏切成6 mm断面行氯化三苯基四氮唑染色和光镜检查。比较相应层面的MRI延迟强化区和氯化三苯基四氮唑染色所示梗死区的关系。 结果与结论：注射Gd-DTPA的延迟成像10 min时强化区面积与氯化三苯基四氮唑染色相比过高估计梗死心肌面积约21%,30 min时强化区面积与氯化三苯基四氮唑染色结果一致,之后则过低估计坏死心肌的面积;注射ECIII-600的延迟磁共振成像在坏死区显示强烈而持续的对比增强,强化区面积与氯化三苯基四氮唑染色所示心肌梗死面积一致。说明ECIII-600增强磁共振延迟成像可以准确反映急性心肌梗死面积。Gd-DTPA评价心肌梗死面积不稳定,观察时间窗短,心脏磁共振成像应在对比剂注射后1 h以内完成。     

大鼠脑缺血再灌注后环氧合酶-2促进E-选择素表达增多及灯盏花素的脑保护作用

目的 观察大鼠脑缺血再灌后环氧合酶-2（COX-2）对E-选择素（E-selectin）表达的影响及灯盏花素对COX-2及E-selectin的影响,探讨脑缺血再灌注损伤后, COX-2加重脑损伤的机制及灯盏花素的脑保护作用。 方法 48只清洁级SD大鼠随机分为假手术组、生理盐水组、SC-58125组、灯盏花素治疗组,在缺血2 h再灌注24 h时,神经功能学评分观察大鼠神经行为的变化,2,3,5-氯化三苯四氮唑（TTC）染色观察大鼠脑梗死灶体积的变化;免疫印迹法和酶联免疫吸附测定检测COX-2及E-selectin表达的变化。 结果 SC-58125组和灯盏花素治疗组神经行为学评分明显降低,脑组织梗死体积显著减小,COX-2和E-selectin的表达明显下降。 结论 脑缺血再灌注后,COX-2可能通过促进E-selectin的表达加重缺血区的炎症反应;灯盏花素可能通过抑制COX-2及E-selectin的表达而发挥脑保护作用。     

Effect of hypothermia on brain cell membrane function and energy metabolism after transient global hypoxia-ischemia in the newborn piglet.

This study was done to determine the effects of hypothermia on brain cell membrane function and energy metabolism after transient hypoxia-ischemia (HI) in the newborn piglet. Cerebral HI was induced by temporarily complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen for 30 min, followed by release of carotid occlusion and normoxic ventilation for 4 hr. Rectal temperature was maintained between 38.0 and 39.0 degrees C in normothermic groups, and between 34.0 and 35.0 degrees C in hypothermic groups for 4 hr after HI. During HI, heart rate, glucose and lactate level in the blood and cerebrospinal fluid increased, and base excess, pH and blood pressure decreased significantly in both normothermic and hypothermic groups. After HI, these abnormalities returned to normal in normothermic group, but lactic acidosis persisted in hypothermic group. Decreased cerebral Na+,K+- ATPase activity and increased lipid peroxidation products, indicative of HI- induced brain injury, were more profound in hypothermic group than in normothermic group. Brain ATP and phosphocreatine levels were not different between normothermic and hypothermic groups. In summary, hypothermia applied immediately after HI for 4 hr did not improve the recovery of brain cell membrane function and energy metabolism in the newborn piglet.     

Effect of electroconvulsive shock (ECS) treatment on the histaminergic system in rat brain: Biochemical and behavioural studies

The effects of electroconvulsive shock (ECS) on brain histamine (HI) levels, 1-histidine decarboxylase (HD) and HI-methyltransferase (HMT) activities, and H₂-receptor-mediated hypothermia were studied in rats.Single (x1) and repeated (x10, once daily) ECS had practically no effect on both HI levels and HMT activities in the rat hypothalamus, cerebral cortex and rest of the brain. ECS x10 significantly increased HI accumulation. ECS x1 (only after 24 h) and ECS x10 resulted in marked elevation of the brain HD activity; the most pronounced effect was observed in the cerebral cortex. Repeated, but not single, ECS reduced the hypothermic action of various centrally given histamine H₂-receptor agonists (HI, 4-methylHI, dimaprit and impromidine).It is suggested that prolonged treatment with ECS activates the central histaminergic system in the rat. The histaminergic neurons in the cerebral cortex seem to be especially affected by repeated ECS.     

JAK2-STAT3信号通路在树鼩脑缺血后适应中的作用机制

 目的：观察JAK2-STAT3信号转导通路在树鼩缺血后适应（ischemic postconditioning,IPoC）神经保护中的调控作用,探讨阻断JAK2-STAT3通路后脑损伤加重的机制。方法：通过光化学反应建立树鼩血栓性脑缺血模型;于缺血后4 h夹闭患侧颈总动脉3次（每次5 min）实施IPoC。于IPoC前10 min侧脑室注射AG490（JAK2抑制剂）后,采用TTC染色观察树鼩脑梗死面积的变化,通过HE染色和电镜观察脑皮层神经元形态改变及超微结构变化,应用Western blot检测IPoC及AG490处理后皮层t-STAT3和p-STAT3蛋白水平的变化。结果：缺血24 h,皮层神经元固缩,线粒体肿胀,嵴溶解;脑梗死面积占半脑面积的（24.78±3.30）%;此时皮层神经元STAT3磷酸化水平明显增高（P<0.01）。IPoC后皮层神经元损伤减轻,线粒体肿胀改善,脑梗死面积占半脑面积的百分比减小为（17.67±1.83）%（P<0.01）,STAT3磷酸化水平进一步增高（P<0.01）。然而,给予AG490处理后,皮层神经元损伤加重,脑梗死面积再次增大为（23.85±2.77）%（P<0.05）,STAT3磷酸化水平则明显降低（P<0.05）。结论：IPoC可能通过调控STAT3的磷酸化而减轻树鼩缺血性脑损伤,抑制JAK2-STAT3信号通路可抵消IPoC的保护效应而加重脑损伤。