Barone F C, Price W J, White R F, Willette R N, Feuerstein G Z
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Neurosci Biobehav Rev. 1992 Summer;16(2):219-33. doi: 10.1016/s0149-7634(05)80182-4.
A review of the sensitivity of genetically hypertensive rats to cerebral ischemia was presented together with original data describing the systematic comparison of the effects of focal ischemia (permanent and temporary with reperfusion) performed in hypertensive and normotensive rats (i.e., blood pressures verified in conscious instrumented rats). Microsurgical techniques were used to isolate and occlude the middle cerebral artery (MCAO) of spontaneously hypertensive (SHR), Sprague-Dawley (SD) and Wistar Kyoto (WKY) rats at the level of the inferior cerebral vein. Following permanent (24 h) MCAO, persistent and similar decreases in local microvascular perfusion (i.e., to 15.6 +/- 1.7% of pre-MCAO levels) were verified in the primary ischemic zone of the cortex for all strains using Laser-Doppler flowmetry. A contralateral hemiplegia that occurred following MCAO, evidenced by forelimb flexion and muscle weakness, was greater in SHR (neurological grade = 2.0 +/- 0.1) than SD (1.0 +/- 0.4) or WKY (0.7 +/- 0.4) rats (N = 7-9, p less than 0.05). SHR also exhibited sensory motor deficits following MCAO compared to sham-operation, with decreased normal placement response of the hindlimb (% normal = 20 vs. 83, N = 23-30, p decreased rota-rod (41 +/- 7 vs. 126 +/- 19 on rod, N = 10-15, p less than 0.05) and balance beam (25 +/- 5 vs. 116 +/- 29 s on beam, N = 5-7, p less than 0.05) performance. However, an index of general motor activity was not affected by permanent MCAO. Triphenyltetrazolium-stained forebrain tissue analyzed by planimetry revealed a significantly larger and more consistent cortical infarction in SHR (hemispheric infarction = 27.9 +/- 1.5%) compared to SD (15.4 +/- 4.1%) and WKY (4.0 +/- 2.4%) rats (N = 7-9, p less than 0.05), occupying predominantly the frontal and parietal areas. Also, a significant degree of ipsilateral hemispheric swelling (4.6 +/- 0.9%, N = 7-9, p less than 0.05) and increased brain water content (78.4 +/- 0.3% to 80.4 +/- 0.2%, N = 8-9, p less than 0.05) was identified in SHR that was not observed in SD or WKY rats. A novel model of temporary MCAO also was evaluated in the hypertensive and normotensive rat strains. Initially, the effect of increasing MCAO-time followed by 24 h reperfusion in SHR was studied. During temporary MCAO (20 to 300 min), persistent and stable decreases in local microvascular perfusion (i.e., to 15-20% of pre-MCAO levels) were verified in the primary ischemic zones of the cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
本文回顾了遗传性高血压大鼠对脑缺血的敏感性，并给出了原始数据，这些数据描述了在高血压大鼠和正常血压大鼠（即在清醒的植入仪器的大鼠中测得的血压）中进行局灶性缺血（永久性和暂时性伴再灌注）效应的系统比较。采用显微外科技术，在大脑下静脉水平分离并阻断自发性高血压大鼠（SHR）、Sprague-Dawley大鼠（SD）和Wistar Kyoto大鼠（WKY）的大脑中动脉（MCAO）。永久性（24小时）MCAO后，使用激光多普勒血流仪在所有品系大鼠的皮质原发性缺血区均证实局部微血管灌注持续且相似地下降（即降至MCAO前水平的15.6±1.7%）。MCAO后出现的对侧偏瘫，表现为前肢屈曲和肌肉无力，在SHR（神经学评分=2.0±0.1）中比SD大鼠（1.0±0.4）或WKY大鼠（0.7±0.4）更严重（N=7-9，p<0.05）。与假手术相比，SHR在MCAO后还表现出感觉运动缺陷，后肢正常放置反应降低（正常百分比=20%对83%，N=23-30，p<0.05），旋转棒性能下降（在棒上的时间为41±7秒对126±19秒，N=10-15，p<0.05），平衡木性能下降（在平衡木上的时间为25±5秒对116±29秒，N=5-7，p<0.05）。然而，一般运动活动指数不受永久性MCAO影响。通过平面测量分析的三苯基四氮唑染色前脑组织显示，与SD大鼠（15.4±4.1%）和WKY大鼠（4.0±2.4%）相比，SHR的皮质梗死明显更大且更一致（半球梗死=27.9±1.5%）（N=7-9，p<0.05），主要占据额叶和顶叶区域。此外，在SHR中发现有明显程度的同侧半球肿胀（4.6±0.9%，N=7-9，p<0.05）和脑含水量增加（从78.4±0.3%增至80.4±0.2%，N=8-9，p<0.05），而在SD或WKY大鼠中未观察到。还在高血压和正常血压大鼠品系中评估了一种新型的暂时性MCAO模型。最初，研究了在SHR中增加MCAO时间后再灌注24小时的效果。在暂时性MCAO（20至300分钟）期间，在皮质的原发性缺血区证实局部微血管灌注持续且稳定地下降（即降至MCAO前水平的15-20%）。（摘要截断于400字）
