PERSISTENCE AND ATROPHY OF SEPTAL DIAGONAL BAND NEURONS EXPRESSING THE P75 NEUROTROPHIN RECEPTOR IN PILOCARPINE-INDUCED CHRONIC EPILEPSY INTHE RAT/

Systemic administration of pilocarpine, which results in status epilep ticus followed by recurrent seizures in rats, is a widely used experim ental model of chronic limbic epilepsy. Marked structural alterations have been documented in pilocarpine-induced epilepsy, and these includ e cell loss in the hippocampus and other brain areas, and sprouting of mossy and cholinergic fibers in the hippocampus. Evidence is accumula ting that neurotrophins and neurotrophin receptors are involved in the cascade of these events. Two and 4 months after pilocarpine-induced e pilepsy, neurons containing the 75-kDa low affinity neurotrophin recep tor (p75(NTR)) were investigated with immunohistochemistry in the medi al septal and diagonal band nuclei. No significant differences in the distribution and number of immunoreactive neurons were found in the ep ileptic rats compared to control saline-treated animals. However, in t he epileptic animals, a significant decrease in the perikaryal size of p75(NTR)-immunoreactive neurons of the septal/diagonal band region wa s found by 60 days, and such atrophic changes were more marked in the diagonal band nuclei by 120 days. These findings indicate that the p75 (NTR)-containing cell bodies, which include the neurons projecting to the hippocampal formation and are cholinergic in the normal brain, sur vive after months of spontaneous recurrent seizures, during which, the refore, a supply of p75NTR to target regions is maintained in the chro nic epileptic brain. However, the present data point out that these p7 5NTR-containing neurons undergo a significant shrinkage in pilocarpine -induced chronic epilepsy, thus indicating that they are involved in t he brain pathology of temporal lube epilepsy. (C) 1998 Elsevier Scienc e B.V. All rights reserved.