Ross D T, Duhaime A C
Department of Clinical Neurosciences, Brown University, Providence, RI.
Brain Res. 1989 Oct 30;501(1):129-43. doi: 10.1016/0006-8993(89)91034-2.
Transient global ischemia was produced in rats by cisternal fluid infusion, producing a negative cerebral perfusion pressure by elevating the intracranial pressure (ICP) 25-50 mm Hg above mean arterial pressure (MAP). Animals were allowed to survive for 2-7 days following a transient ischemic episode of 5-30 min. The brains were examined for signs of ischemic degeneration in Nissl-stained sections and adjacent sections reacted with antisera against glial fibrillary acidic protein (GFAP) or aspartate aminotransferase (AAT). Neurons in the thalamic reticular nucleus (RT), a pure population of gamma-aminobutyric acid (GABA)ergic neurons which project their axons to thalamic relay nuclei, were found to have the lowest threshold for degeneration in this model, consistently undergoing degeneration under conditions which completely spared the hippocampal CA1 from degeneration. Whereas it took up to 30 min of complete ischemia to produce degeneration of CA1 neurons when ICP was raised using room temperature infusion fluids, 15 min of ischemia under these conditions was sufficient to produce extensive degeneration of neurons in the entire ventral 3/4 of the RT. Prolonged (greater than 25 min) episodes of partial ischemia (ICP less than or equal to MAP) were also sufficient to produce massive degeneration of RT neurons. The lesion in the RT was most clearly evident in sections reacted with antisera to GFAP, labeling intensely reactive protoplasmic astrocytes within the regions of the RT where neuronal degeneration had occurred. Neuronal loss and accompanying proliferation of microglial cells were evident in Nissl-stained sections but the extent of the neuronal loss was most clearly obvious in sections reacted with an antisera to AAT, an enzyme present in detectable quantities in GABAergic neurons. Pretreatment with the non-competitive NMDA antagonist MK-801 at doses sufficient to completely prevent massive degeneration of the hippocampal CA1 failed to prevent the degeneration of RT neurons, suggesting that if RT degeneration involves an excitotoxic process it acts through non-NMDA receptors.
通过脑池内输注液体在大鼠中诱导短暂性全脑缺血，将颅内压（ICP）升高至高于平均动脉压（MAP）25 - 50 mmHg，从而产生负性脑灌注压。在经历5 - 30分钟的短暂缺血发作后，让动物存活2 - 7天。对大脑进行检查，在尼氏染色切片以及与抗胶质纤维酸性蛋白（GFAP）或天冬氨酸转氨酶（AAT）抗血清反应的相邻切片中寻找缺血性变性的迹象。丘脑网状核（RT）中的神经元，这是一群纯的γ-氨基丁酸（GABA）能神经元，其轴突投射到丘脑中继核，在该模型中被发现具有最低的变性阈值，在完全使海马CA1免于变性的条件下持续发生变性。当使用室温输注液升高ICP时，需要长达30分钟的完全缺血才能使CA1神经元发生变性，而在这些条件下15分钟的缺血就足以使整个RT腹侧3/4的神经元发生广泛变性。延长（大于25分钟）的部分缺血发作（ICP小于或等于MAP）也足以导致RT神经元大量变性。RT中的病变在与抗GFAP抗血清反应的切片中最为明显，在RT中神经元发生变性的区域标记出强烈反应性的原浆性星形胶质细胞。在尼氏染色切片中可见神经元丢失以及伴随的小胶质细胞增殖，但在与抗AAT抗血清反应的切片中神经元丢失的程度最为明显，AAT是一种在GABA能神经元中可检测到的酶。用足以完全预防海马CA1大量变性的剂量的非竞争性NMDA拮抗剂MK - 801进行预处理未能预防RT神经元的变性，这表明如果RT变性涉及兴奋性毒性过程，它是通过非NMDA受体起作用的。
