Periodic acid-Schiff (PAS)-positive deposits in brain following kainic acid-induced seizures: relationships to fos induction, neuronal necrosis, reactive gliosis, and blood-brain barrier breakdown.

Abstract

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.