Effect of TTX suppression of hippocampal activity following status epilepticus.
Status epilepticus (SE) is a severe neurological condition that can result in brain damage. In animals, SE is associated with cell loss and aberrant synaptogenesis. These pathological processes appear to be activity-dependent and may continue after the SE has ended. We postulated that suppression of electrical activity following SE at the site of the epileptic focus will reduce seizure-induced damage. To achieve this goal, tetrodotoxin (TTX) was used to suppress electrical activity in the hippocampi bilaterally following SE. Adult rats experienced lithium-pilocarpine-induced SE for 2h while controls underwent sham-SE with saline injections. Starting 12h after the SE or sham-SE rats received either continuous TTX (1 microM) or saline infusions through cannulas implanted in the bilateral hippocampi for 5h daily for 4 days. TTX resulted in significant EEG suppression and reduction in spikes and sharp waves. Rats were sacrificed 2 weeks after SE and the brains examined for cell loss and sprouting. Rats receiving TTX following SE had significantly more cell loss as well as a trend toward more mossy fiber sprouting than saline-treated rats following SE. TTX injection in sham-SE rats caused no cell loss or mossy fiber sprouting. These results suggest that suppression of electrical activity following SE is detrimental.
Zhao
Qian
Q
Neuroscience Center at Dartmouth, Department of Neurology, Dartmouth Medical School, Hanover, NH 03756, USA. qian.zhao@Dartmouth.edu
Raghavendra
Meghana
M
Holmes
Gregory L
GL
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D018021:Lithium Chloride; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D013779:Tetrodotoxin / Q000494:pharmacology* / Q000627:therapeutic use
D000779:Anesthetics, Local; D010862:Pilocarpine; D013779:Tetrodotoxin; D018021:Lithium Chloride