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

(P)eriodic 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 unknow n. In the present study, we demonstrate that the kainic acid model of limbic status epilepticus provides a useful system for the study of PA S-positive staining. The relationship between PAS-positive deposition, induction of fos-like immunoreactivity (FLI), neuronal necrosis, reac tive gliosis, and blood-brain barrier breakdown following the kainic a cid induction of status epilepticus was investigated. Epileptiform act ivity 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 af ter drug injection. Four distinct types of PAS-positive staining in ra t brain were observed: type 1, extracellular matrix (ECM) or blood ves sel associated-material; type 2, granular deposits; type 3, glial labe lling; and type 4, neuronal labelling. Results demonstrated that the f our 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 majo rity of type 3 glia were identified as reactive astrocytes, while a mi nority of appeared to be proliferating microglia; (3) type 1 blood ves sels labelled hemorrhaging vasculature; (4) early deposition of type 2 granules was predictive of subsequent cell loss; (5) chronic type 2 g ranular deposits and type 4 neuronal labelling not associated with cel l death could be predicted by early changes in FLI; and (6) chronic de position of all four forms of PAS-positive material was correlated wit h earlier, transient blood-brain barrier compromise. The results suppo rt the growing literature that local carbohydrate metabolism may be on e of a constellation of parameters important to the development of pro gressive neurodegeneration.