Pilocarpine-induced status epilepticus in rats involves ischemic and excitotoxic mechanisms.
The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology.
Fabene
Paolo Francesco
PF
Section of Anatomy and Histology, Department of Morphological and Biomedical Sciences, University of Verona, Verona, Italy. paolo@anatomy.univr.it
Merigo
Flavia
F
Galiè
Mirco
M
Benati
Donatella
D
Bernardi
Paolo
P
Farace
Paolo
P
Nicolato
Elena
E
Marzola
Pasquina
P
Sbarbati
Andrea
A
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005911:Gliosis / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007511:Ischemia; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D046529:Microscopy, Electron, Transmission; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009474:Neurons / Q000473:pathology; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced*
D018721:Muscarinic Agonists; D010862:Pilocarpine