Bennett S A, Stevenson B, Staines W A, Roberts D C
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Acta Neuropathol. 1995;89(2):126-38. doi: 10.1007/BF00296356.
Periodic acid-Schiff (PAS)-positive deposits have been demonstrated in the central nervous system (CNS) of patients suffering from a wide variety of neurodegenerative disorders including Alzheimer's disease, presenile dementia, Parkinson's disease, diabetes mellitus, myoclonic epilepsy, and cerebral palsy. The etiology of these deposits and their relationship to mechanisms of progressive neurodegeneration is unknown. In the present study, we demonstrate that the kainic acid model of limbic status epilepticus provides a useful system for the study of PAS-positive staining. The relationship between PAS-positive deposition, induction of fos-like immunoreactivity (FLI), neuronal necrosis, reactive gliosis, and blood-brain barrier breakdown following the kainic acid induction of status epilepticus was investigated. Epileptiform activity was elicited in rats by intraperitoneal administration of 10 mg/kg kainic acid and brains were examined 3, 5, 12, 24, 72, and 168 h after drug injection. Four distinct types of PAS-positive staining in rat brain were observed: type 1, extracellular matrix (ECM) or blood vessel associated-material; type 2, granular deposits; type 3, glial labelling; and type 4, neuronal labelling. Results demonstrated that the four types of PAS-positive staining were differentially associated with specific markers of neuropathology: (1) type 1 ECM staining and type 3 glia were preferentially localized to edematous tissue; (2) the majority of type 3 glia were identified as reactive astrocytes, while a minority of appeared to be proliferating microglia; (3) type 1 blood vessels labelled hemorrhaging vasculature; (4) early deposition of type 2 granules was predictive of subsequent cell loss; (5) chronic type 2 granular deposits and type 4 neuronal labelling not associated with cell death could be predicted by early changes in FLI; and (6) chronic deposition of all four forms of PAS-positive material was correlated with earlier, transient blood-brain barrier compromise. The results support the growing literature that local carbohydrate metabolism may be one of a constellation of parameters important to the development of progressive neurodegeneration.
在患有包括阿尔茨海默病、早老性痴呆、帕金森病、糖尿病、肌阵挛性癫痫和脑瘫在内的多种神经退行性疾病的患者中枢神经系统（CNS）中，已证实存在过碘酸希夫（PAS）阳性沉积物。这些沉积物的病因及其与进行性神经退行性变机制的关系尚不清楚。在本研究中，我们证明边缘性癫痫持续状态的 kainic 酸模型为研究 PAS 阳性染色提供了一个有用的系统。研究了 kainic 酸诱导癫痫持续状态后 PAS 阳性沉积、fos 样免疫反应性（FLI）诱导、神经元坏死、反应性胶质增生和血脑屏障破坏之间的关系。通过腹腔注射 10 mg/kg kainic 酸在大鼠中引发癫痫样活动，并在药物注射后 3、5、12、24、72 和 168 小时检查大脑。在大鼠脑中观察到四种不同类型的 PAS 阳性染色：1 型，细胞外基质（ECM）或血管相关物质；2 型，颗粒沉积物；3 型，胶质细胞标记；4 型，神经元标记。结果表明，这四种类型的 PAS 阳性染色与神经病理学的特定标志物存在差异关联：（1）1 型 ECM 染色和 3 型胶质细胞优先定位于水肿组织；（2）大多数 3 型胶质细胞被鉴定为反应性星形胶质细胞，而少数似乎是增殖的小胶质细胞；（3）1 型血管标记出血性脉管系统；（4）2 型颗粒的早期沉积可预测随后的细胞丢失；（5）早期 FLI 变化可预测与细胞死亡无关的慢性 2 型颗粒沉积物和 4 型神经元标记；（6）所有四种形式的 PAS 阳性物质的慢性沉积与早期短暂的血脑屏障损害相关。这些结果支持了越来越多的文献观点，即局部碳水化合物代谢可能是对进行性神经退行性变发展至关重要的一系列参数之一。
