Induction of ornithine decarboxylase mRNA in cerebral cortex in response to kainate lesion of nucleus basalis: involvement of NMDA receptors

Excitotoxin lesion of nucleus basalis with kainate or ibotenate results in degeneration of cholinergic neurones and a subsequent cholinergic deficit in cerebral cortex ipsilateral to the lesion. This lesion is accompanied by a massive increase in ornithine decarboxylase (ODC) activity in ipsilateral cortex, which was further investigated in this study by assay of levels of ODC mRNA in cerebral cortex after lesion. Injection of kainate into the nucleus basalis induced a significant increase in ODC mRNA in ipsilateral cerebral cortex which was maximal at 8 h after lesion and declined to control levels by 72 h. This induction showed clear regional specificity and was completely prevented by injection of an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, at a dose of 1 mg/kg, 2 h after excitotoxin lesion. This study indicates that excitotoxin lesion causes an early and transient increase in ODC mRNA that is mediated by NMDA receptors and may represent a physiological response to injury.     

脑缺血大鼠大脑皮质NMDA受体的早期表达

目的　探讨脑缺血和缺血再灌注早期大脑皮质NMDA受体的变化规律。方法　健康雄性SD大鼠 4 8只 ,随机分为 6组 :假手术对照组、单纯脑缺血 1 5min、2 0min和 30min组及脑缺血 1 5min再灌流 30min和 2 4h组 ;4血管脑缺血动物模型 ;连续冰冻冠状切片观察 ,NR1 免疫组化染色特异性地显著NMDA受体的变化 ,图象分析及计算阳性单位PU值。结果　①单纯脑缺血各组PU值分别为 7 5 5± 1 81、6 91± 2 5 3和 6 0 9± 1 5 0 ,与对照组PU值 9 0 4± 1 5 7相比呈下降趋势 (P≤ 0 0 5 ) ;②再灌流 30min和 2 4h组PU值分别为 5 76± 2 2 4和 4 73± 1 34,与对照组PU值相比明显减少 36 2 9%～ 4 7 6 8% ,有统计学意义(P <0 0 5 ) ;③再灌流 0min、30min和 2 4h组两两比较 ,除 2 4h和 0min组相比NR1 阳性反应物减少有统计学意义 (P <0 0 5 )外 ,其它组别间NMDA受体下降的变化无显著性差异 (P >0 0 5 )。结论　脑缺血和缺血再灌流早期NMDA受体都存在下行调节 ,这种调节可能是一种保护性作用     

Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits

Bis(7)-tacrine, a promising anti-Alzheimer's dimer, has been shown to have multiple neuroprotective activities in vitro. Here, we investigate whether bis(7)-tacrine attenuates focal cerebral ischemic impairment in vivo. Cerebral ischemia was induced in Sprague-Dawley rats by transient (2h) middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Bis(7)-tacrine administered intraperitoneally 15 min after ischemia dose-dependently improved neurological behavior deficits and reduced both cerebral infarct volume and edema. The TUNEL staining assay showed that bis(7)-tacrine attenuated neuronal apoptosis in the penumbral region. Compared with that for memantine, a moderately effective N-methyl-d-aspartate (NMDA) receptor antagonist with a similar affinity and potency to bis(7)-tacrine in blocking NMDA receptors, the therapeutic window for bis(7)-tacrine was wider and lasted up to 6h after the onset of ischemia. Bis(7)-tacrine did not affect physiological parameters or regional cerebral blood flow during either the occlusion period or the early reperfusion stage. In conclusion, bis(7)-tacrine dose- and time-dependently protected against acute focal cerebral ischemic insults, possibly through the drug's anti-apoptotic effects during multiple events in the ischemic cascade.     

Angiotensin type 1 receptor blockage improves ischemic injury following transient focal cerebral ischemia

Following cerebral ischemia, i.v. infusion of angiotensin II increases cerebral edema and mortality. Angiotensin type 1 receptor blockage should therefore improve acute cerebral ischemia. Left middle cerebral artery occlusion (120 min) followed by reperfusion was performed with the thread method under halothane anesthesia in Sprague-Dawley rats. Olmesartan (angiotensin type 1 receptor blocker; 0.01 or 0.1mumol/kg/h) was infused i.p. for 7 days following middle cerebral artery occlusion followed by reperfusion. Stroke index score, infarct volume, specific gravity, and brain angiotensin II and matrix metalloproteinases were quantified in the ischemic and non-ischemic hemispheres. Olmesartan treatment improved stroke index score, infarct volume, and cerebral edema in our cerebral ischemia model. In particular, stroke index score, infarct volume, and cerebral edema were reduced even with a low dose of olmesartan that did not decrease blood pressure. Paralleling these effects on cerebral ischemia, olmesartan treatment also reduced the reactive upregulation in brain angiotensin II, matrix metalloproteinase-2, matrix metalloproteinase-9, and membrane type 1-matrix metalloproteinase in the ischemic area. Angiotensin type 1 receptor stimulation may be one of the important factors that cause cerebral edema following cerebral ischemia, and that its inhibition may be of therapeutic advantage in cerebral ischemia.     

Resveratrol preconditioning induces cellular stress proteins and is mediated via NMDA and estrogen receptors

Resveratrol pretreatment has been shown to provide neuroprotection in models of cerebral ischemia. This phenomenon, commonly termed preconditioning, promotes ischemic tolerance and may involve mild activation of endoplasmic reticulum stress pathways in the affected tissue. Systemic injection of resveratrol (2×10⁻³, 2×10⁻⁴, 1×10⁻⁴ mg/kg) 30 min prior to a 4 h period of right middle cerebral artery occlusion significantly reduced infarct area in the insular region of rat prefrontal cortex. This affect was blocked when resveratrol treatment was combined with a non-selective estrogen receptor antagonist, or preceded by intracortical injection of an NMDA receptor antagonist. The neuroprotective effect of resveratrol was associated with reduced renal sympathetic nerve activity as well as induction of resident endoplasmic reticulum chaperone proteins, glucose-regulated proteins 78 and 94. The calcium-sensitive chaperone heat shock protein 70 and the cysteine protease m calpain did not respond to resveratrol pretreatment. However, a significant induction of heat shock protein 70 was observed in the contralateral cortex of resveratrol pretreated rats following 4 h of right middle cerebral artery occlusion. These data suggest that resveratrol preconditioning promotes ischemic tolerance in the short term, in part via effects mediated through activation of estrogen and NMDA receptors, as well as through mild activation of cellular stress proteins.     

Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia

Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.     

缓激肽受体抑制剂对脑缺血再灌注大鼠的脑保护作用

为了探讨缓激肽及其受体在脑缺血急性期对血脑屏障通透性及炎症因子分泌的影响,本研究采用线栓法制作大鼠大脑中动脉梗塞(MCAO)模型,分别应用缓激肽B1和B2受体的特异性抑制剂,在缺血再灌流后24h进行动物行为学评分,TTC染色计算梗死体积,伊文斯蓝染色检测血脑屏障通透性,透射电镜观测血脑屏障超微结构的变化,ELISA对缺血区IL-1β、TNF-α、PGE2进行测定。结果显示:缓激肽B1和B2受体抑制剂能够改善脑缺血大鼠急性期行为学评分、缩小梗死体积、降低血脑屏障通透性、维持血脑屏障结构完整、抑制炎症因子分泌,缓激肽B2受体抑制剂的上述效果优于B1受体抑制剂。以上结果提示缓激肽在脑缺血急性期可以加重脑损伤,其受体的特异性抑制剂可以减轻脑损伤。     

Do polyamines regulate the NMDA inhibition of muscarinic receptor-induced phosphoinositide turnover in guinea pig brain?

The N-methyl-D-aspartate (NMDA) receptor-induced inhibition of muscarinic receptor-stimulated phosphoinositide turnover in guinea pig cerebral cortical slices was investigated to determine whether polyamines regulate the function of NMDA in this system. None of the polyamines tested produced significant stimulation of phosphoinositide turnover. Neither spermine nor the substituted polyamine philanthotoxin-343 altered the inhibitory effect of NMDA. The simpler substituted polyamines N-(4-hydroxyphenylpropanoyl)-spermine and N-(4-hydroxyphenylacetyl)-spermine, however, antaganised the NMDA receptor inhibition of the muscarinic response with low affinity (Ki greater than or equal to 100 microM). Diethylenetriamine, a purported polyamine antagonist of the NMDA receptor, was without effect on the NMDA inhibitory response, as was ifenprodil, a structurally unrelated compound with reported antagonist capacity. In summary, therefore, we fail to observe polyamine regulation of the NMDA receptor mediating an inhibition of the muscarinic phosphoinositide turnover response in guinea pig cerebral cortical slices.     

脑缺血及再灌流早期大鼠海马CA1区NMDA受体的变化

探讨脑缺血和缺血再灌流早期海马CA1 区NMDA受体的变化规律,选用雄性SD大鼠 48只,随机分为:假手术对照组、单纯脑缺血 15min、20min和 30min组及脑缺血 15min再灌流 0min、30min和 24h组,参照Pulsinelli Brierley(4VO)法制作脑缺血模型,取脑,连续冰冻冠状切片,NR1免疫组化染色并进行图像分析及计算阳性单位PU值。结果显示: (1 )单纯脑缺血 15min、20min和 30min组PU值分别为 5. 89±0. 92、5. 18±1. 63和 4. 89±2. 69,与对照组PU值 7. 56±2. 35相比,下降 22. 09% ~35. 32% (P≤0.05); (2)再灌流 30min和 24h组PU值分别为 4. 20±1. 37和 2. 99±1. 28,与对照组PU值相比,减少 44. 44% ~60. 45%,有统计学意义(P<0.05),均明显降低; (3)再灌流 0min、30min和 24h组两两比较, 24h和 0min组的NMDA受体减少有统计学意义(P<0.05)。上述结果提示,脑缺血和缺血再灌流早期海马CA1 区NMDA受体存在下行调节,这可能是脑缺血后自身的一种保护性调节。     

Intracerebroventricular injection of a neuropeptide Y-Y1 receptor agonist increases while BIBP3226, a Y1 antagonist,reduces the infarct volume following transient middle cerebral artery occlusion in rats

Recent studies using middle cerebral artery occlusion in the rat have suggested a role of neuropeptide Y in ischemic pathophysiology. In this study, we investigated the effects of an i.c.v. injection of a neuropeptide Y-Y2 receptor agonist, neuropeptide Y 3-36, a Y1 receptor agonist, [Leu(31),Pro(34)]-neuropeptide Y, or a Y1 receptor antagonist, BIBP3226, on infarct volume and hemodynamic parameters following middle cerebral artery occlusion. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 2 h. A single i.c.v. injection of neuropeptide Y 3-36 (15 microg/kg), [Leu(31),Pro(34)]-neuropeptide Y (30 microg/kg), or BIBP3226 (5, 15, or 45 microg/kg) was given at 30 min of ischemia. Blood pressure, heart rate, and regional cerebral perfusion were monitored during ischemia and reperfusion. The rats were decapitated after 70 h of reperfusion, and their brains were cut into 2-mm-thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. When compared with an infarct volume of 17.4+/-4.4% of the ipsilateral hemisphere following injection of neuropeptide Y 3-36, administration of the Y1 receptor analogs significantly modified the infarct volume (ordinary one-way analysis of variance (ANOVA), P<0.0001). [Leu(31),Pro(34)]-neuropeptide Y increased the infarct volume to 32.0+/-4.1% (Student-Newman-Keuls post-test, P<0.01), whereas BIBP3226 at 15 microg/kg decreased the infarct volume to 6.5+/-1.0% (post-test P<0.05). Although there was no major difference in the hemodynamic parameters among the groups, injection of [Leu(31),Pro(34)]-neuropeptide Y tended to further reduce cerebral perfusion during ischemia, while injection of BIBP3226 at 15 microg/kg appeared to have the opposite effect. In addition to glutamate, calcium ion and nitric oxide, activation of the neuropeptide Y-Y1 receptors may mediate cerebral damage during focal ischemia. Conversely, inhibiting the Y1 receptors may protect the brain against ischemic injury. Further studies are warranted to confirm the neuroprotective potential of neuropeptide Y-Y1 receptor inhibition.     

脑的不对称性影响大鼠局灶性脑缺血的结局

为评价左右侧大脑中动脉闭塞(MCAO)对右利大鼠神经行为功能和脑梗死体积的影响,本研究应用四足动物觅食实验筛选右利爪雄性SD大鼠24只,随机分为经左、右侧插线组各12只,8%水合氯醛腹腔注射(300mg/kg)麻醉,线栓法经左、右侧颈外-内动脉插入头端涂有多聚赖氨酸的4-0尼龙线,建立大鼠MCAO缺血2h模型,再灌注72h后评价动物的神经行为功能,测量脑梗死体积。结果表明,所有动物在脑缺血2h神经功能缺损评分最高,再灌注1、24、48和72h经左侧MCAO大鼠显著高于经右侧MCAO大鼠(P<0.05),后者功能明显优于前者,脑梗死体积经左侧插线的大鼠显著大于经右侧插线的大鼠(P<0.05)。研究结果提示,大鼠主侧半球大脑中动脉缺血后,神经功能缺损和脑梗死体积较对侧严重,脑的不对称性影响大鼠局灶性脑缺血的最终结局。     

Alexia without agraphia

Alexia without agraphia (also called pure alexia or word blindness) was the first of the disconnection syndromes (syndromes caused by disconnection of the right from the left cerebral hemisphere through interruption of the communication pathways between them) to be described. Déjerine in 1892 reported a patient who developed this syndrome after an infarct of the left occipital lobe and splenium of the corpus callosum. We describe a patient who developed alexia without agraphia due to an embolic left occipital lobe infarct extending to the posterior commissure and splenium of the corpus callosum.     

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     

NMDA and age dependent cerebral hemodynamics after traumatic brain injury.

Activation of N-methyl-D-aspartate (NMDA) glutamatergic receptors elicits cerebrovascular dilation, may couple local cerebral metabolism to blood flow but contribute to excitotoxic neuronal cell death. While cerebral hemodynamics following traumatic brain injury may correlate with neurologic status, the role of NMDA vascular activity is uncertain in the sequelae of brain injury. NMDA dilation was impaired following fluid percussion brain injury (FPI) in an age dependent manner in the pig and the newly described opioid nociceptin/orphanin FQ (NOC/ oFQ) contributes to such impairment via the cyclooxygenase dependent generation of superoxide. Further, hypotensive pial artery dilation (PAD) was blunted after FPI but partially protected by pretreatment with the NMDA antagonist MK801. Cerebral blood flow (CBF) was reduced during normotension by FPI, further reduced by hypotension, but both were partially protected by MK801 in the newborn. In contrast, blunted hypotensive PAD was protected significantly less by MK801 in the juvenile pig. Similarly, MK801 had less protective effect on normotensive and hypotensive CBF values post FPI in the juvenile. These data indicate that NMDA receptor activation contributes to impaired hypotensive cerebral hemodynamics following FPI in an age dependent manner. Further, these data suggest that NMDA receptor activation, NOC/oFQ, and prostaglandins dynamically interact to impair cerebral hemodynamics following FPI.     

Antagonism of NMDA receptors by butanesulfonyl-homospermine guanidine and neuroprotective effects in in vitro and in vivo

The polyamine derivative BsHSPMG (butanesulfonyl-homospermine with guanidine group) was found to inhibit macroscopic currents strongly at heteromeric N-methyl-d-aspartate (NMDA) receptors (NR1/NR2A and NR1/NR2B) and Ca²⁺-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (homomeric glutamate receptor 1) receptors expressed in Xenopus laevis oocytes on voltage-clamp recording. The IC₅₀ values of BsHSPMG for NR1/NR2A, NR1/NR2B, NR1/NR2C, and NR1/NR2D receptors were 0.016, 0.021, 5.4, and 9.0 μM, respectively. BsHSPMG inhibited the activity of NR1/NR2A and NR1/NR2B receptors more strongly and did it for those of NR1/NR2C and NR1/NR2D receptors more weakly than a therapeutic drug of Alzheimer's disease, memantine. The inhibition by BsHSPMG was voltage-dependent, since it was prominent at −100 mV compared to that at −20 mV. Mutations including NR1 N616Q, E621Q, N650A, L655A, T807C, NR2B W559L, M562S, W607L, N616Q, and V620E, among others, reduced the inhibition by BsHSPMG, suggesting that BsHSPMG penetrates the channel pore of NMDA receptors deeply. The toxicity of BsHSPMG in neuroblastoma SH-SY5Y cells was much weaker than that of memantine. The effect of BsHSPMG was measured on the focal cerebral ischemia induced by occlusion (1 h) of the middle cerebral artery in mice. BsHSPMG applied before or after occlusion greatly reduced the volume of infarct in mice. These findings demonstrate that BsHSPMG penetrates the NMDA channel pore and exhibits neuroprotective effects against excitatory toxicity in mice.     

Netrin-1 attenuates ischemic stroke-induced apoptosis

In the present study we tested the protective effects of netrin-1 in stroke and investigated the potential underlying mechanisms. When we performed middle cerebral artery occlusion (MCAO) on adult mice, up-regulation of the receptor uncoordinated gene 5H2 (UNC5H2) but not its ligand netrin-1 was detected with RT-PCR and immunohistochemistry. Injection of netrin-1, 1 day after MCAO, significantly reduced infarct volume at 3 days after MCAO as revealed by functional magnetic resonance imaging. The ischemic cortex was preserved when netrin-1 was continuously administered. Fluoro-Jade and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining showed that netrin-1 reduced the number of dying neurons and apoptotic cells after MCAO. Ischemia-induced p53 expression was attenuated by netrin-1. We also tested the ability of netrin-1 to attract intrinsic neuronal stem cells to the infarct area. Both DCC and UNC5H2 were expressed in neurosphere culture and netrin-1 attracted stem cells in an in vitro transwell assay. However, in vivo netrin-1 administration did not enhance the MCAO-induced stem cell migration toward the infarct area. Our study shows that UNC5H2 expression was elevated after MCAO and administration of netrin-1 protected infarct tissue from p53-mediated apoptosis. These data indicate that the p53/dependent receptor pathway is involved in ischemic stroke pathology and suggest possible new stroke therapies.     

鸟氨酸脱羧酶/多胺系统在大鼠缺血预适应心肌保护中的作用

目的：探讨鸟氨酸脱羧酶（ODC）/多胺系统在缺血预适应（IPC）心肌保护中的作用。方法:应用离体灌流大鼠心脏复制模拟心肌缺血/再灌注模型。心脏随机分为6组：对照组 (control)、缺血/再灌注组 (IR)、弱缺血预适应组 (IPCw)、强缺血预适应组 (IPCs)、IPCw+多胺抑制剂组 (DF-EG-IPCw)和IPCs+多胺抑制剂组(DF-EG-IPCs)。免疫印迹法定量分析多胺合成限速酶鸟氨酸脱羧酶 (ODC)的表达;高效液相色谱测定心肌组织中的多胺（腐胺、精脒、精胺）含量;Powerlab多导生理记录系统记录心脏功能;氯化三苯基四氮唑 (TTC) 染色检测心肌梗死面积;TUNEL方法检测细胞凋亡率,比较其中的差异性。结果:（1）与对照组比,IR组ODC表达下调,腐胺含量增加,精胺含量减少,总多胺池减少（P<0.05）,此时心功能下降（LVDP、HR、CF均低于对照组,P<0.05）,心肌梗死面积及心肌细胞凋亡率增加（P<0.05）;（2）与IR组比,弱及强缺血预处理组（IPCw、IPCs）心肌ODC表达上调,腐胺含量减少,精胺含量增加,总多胺池增加（P<0.05或P<0.01）,此时大鼠心功能有明显改善（LVDP、HR、CF与IR组比,P<0.05）,心肌梗死面积及心肌细胞凋亡率均明显降低（P<0.01）;（3）给予多胺抑制剂后,心肌ODC表达,腐胺、精脒、精胺及总多胺池含量均明显降低（DF-EG-IPCw组 vs IPCw组;DF-EG-IPCs组vs IPCs组,P<0.05或P<0.01）,心功能明显下降（P<0.05）,心肌梗死面积及细胞凋亡率均明显增加（P<0.05）。结论:缺血预适应能明显上调大鼠心肌ODC/多胺系统,减轻缺血/再灌注心肌损伤;多胺合成代谢抑制剂取消了预适应介导的心功能改善、缩小心肌梗死面积及减少心肌细胞凋亡的作用,提示ODC/多胺系统可能参与了缺血预适应介导的心肌保护作用。     

The specific NMDA receptor antagonist AP-7 attenuates focal ischemic brain injury

Pharmacologic blockade of excitatory amino acid receptors, especially the N-methyl-D-aspartate-preferring subclass of glutamate receptors, has been shown to reduce neuronal damage in models of global cerebral ischemia followed by reperfusion. The pharmacologic blockade at the NMDA receptor attenuates infarct size following permanent focal vascular occlusion in brain. Functional recovery is improved as well. These effects were seen with treatment begun 15 min following the stroke.     

Facilitatory effect of docosahexaenoic acid on N-methyl-D-aspartate response in pyramidal neurones of rat cerebral cortex.

1. The effect of docosahexaenoic acid (DHA) on N-methyl-D-aspartic acid (NMDA) responses in the presence of glycine was investigated in pyramidal neurons acutely dissociated from rat cerebral cortex in whole-cell and single channel configurations. 2. DHA potentiated the NMDA-induced response but reduced the non-NMDA (kainate-induced) response in a concentration-dependent manner at a holding potential of -60 mV under voltage-clamp conditions. 3. Arachidonic acid (AA) also potentiated the NMDA-induced response in a manner similar to DHA. Oleic acid caused a slight potentiation. However, other polyunsaturated and saturated fatty acids had no such effects. 4. The facilitatory action of DHA on the NMDA-induced response was not affected by adding inhibitors of cyclo-oxygenase, lipoxygenase or phospholipase A2, suggesting that DHA may exert its facilitatory effect directly on the NMDA receptor. 5. The facilitatory action of DHA was observed in the presence of a saturating dose of NMDA. Moreover, a detailed analysis of the NMDA receptor-operated single channel currents revealed that, in the presence of DHA, the open probability of the channel increased without changing the conductance, indicating that DHA may act by binding directly to a novel site on the NMDA receptor or by altering the lipid environment of the NMDA receptor and thereby potentiating the response to NMDA. 6. The results are discussed in terms of the possibility that DHA may play an important role in the genesis of long-term potentiation, at least that involving the activation of NMDA receptors.     

锥体束行程上无症状性腔隙性脑梗死大脑脚面积及FA值变化特点

目的探讨锥体束行程上无症状性腔隙性脑梗死大脑脚面积和FA值变化特点及临床意义。方法选取经核磁共振检查检确诊为锥体束行程上无症状性腔隙性脑梗死病人54例及正常人群组105例为研究对象,54例病人的大脑脚面积及FA值按梗死灶累及侧别,分为患侧组及健侧组并与对照组的左侧和右侧大脑脚的面积及FA值进行比较,同时比较了腔梗组和对照组的大脑脚面积及FA值的不对称比。结果无症状腔隙性脑梗死组双侧大脑脚面积小于对照组(左侧F=17.104,P=0.000,右侧F=12.581,P=0.000),双大脑脚的FA值无差异(左侧P=0.894,右侧P=0.968)。腔梗组双侧大脑脚面积及FA值无差异(分别为t=0.254 P=0.8,t=0.268 P=0.790),腔梗组与对照组双大脑脚面积及FA值不对称比值无差异(分别为t=0.114 P=0.67,t=1.463 P=0.175)。结论无症状性腔隙性脑梗死对于局限性脑梗死所引起Wallerian变性而导致的大脑脚面积及FA值的改变的无影响。