Hernandez N E, MacDonall J S, Stier C T, Belmonte A, Fernandez R, Karpiak S E
Division of Neuroscience, New York Psychiatric Institute, New York.
Exp Neurol. 1994 Mar;126(1):95-100. doi: 10.1006/exnr.1994.1045.
Many reports indicate that GM1 ganglioside is effective in reducing CNS ischemic injury in animal models. These models employ invasive surgery to induce ischemic damage in otherwise healthy animals. The purpose of this study was to determine if the beneficial effects of GM1 could be generalized to Spontaneously Hypertensive Rats-Stroke Prone (SHRSP). The SHRSP strain develops a pathology similar to those observed in patients with stroke. The SHRSP have "risk" factors that include hypertension, fibrinoid necrosis, and sensitivity to diet. Female SHRSP were randomly assigned to GM1- or saline-treatment conditions. Rats were fed a stroke-inducing diet. Daily body weights, weekly blood pressure, time of stroke onset, and age at death were recorded. Spontaneous activity and performance on a tail-hang test were assessed thrice weekly. The results indicate that GM1 treatment did not delay the time of stroke onset or death. GM1 did reduce hyperactivity in the initial stages of the ischemic pathology, but did not prevent the marked decline in behavioral activity observed at later time points. There were no differences in weight loss, performance on the tail-hang test, or number of CNS injury-related symptoms observed. These findings suggest that GM1 was not as effective in decreasing mortality, weight loss, or behavioral deficits in SHRSP as previously reported using other animal models of ischemia. Distinguishing between those animal models in which GM1 is more and less effective may be useful in determining under which clinical situations GM1 is likely to be most suitable.
许多报告表明,GM1神经节苷脂在动物模型中可有效减轻中枢神经系统缺血性损伤。这些模型采用侵入性手术在原本健康的动物身上诱导缺血性损伤。本研究的目的是确定GM1的有益效果是否可推广至易患中风的自发性高血压大鼠(SHRSP)。SHRSP品系所产生的病理情况与中风患者中观察到的相似。SHRSP具有包括高血压、纤维蛋白样坏死和对饮食敏感等“风险”因素。将雌性SHRSP随机分配至GM1治疗组或生理盐水治疗组。给大鼠喂食诱发中风的饮食。记录每日体重、每周血压、中风发作时间和死亡年龄。每周三次评估自发活动和悬尾试验表现。结果表明,GM1治疗并未延迟中风发作时间或死亡时间。GM1确实在缺血性病理初期降低了多动,但并未防止在后续时间点观察到的行为活动显著下降。在体重减轻、悬尾试验表现或观察到的中枢神经系统损伤相关症状数量方面没有差异。这些发现表明,GM1在降低SHRSP的死亡率、体重减轻或行为缺陷方面并不像先前使用其他缺血动物模型所报告的那样有效。区分GM1效果较好和较差的动物模型可能有助于确定GM1最适合在哪种临床情况下使用。