Electroshocks delay seizures and subsequent epileptogenesis but do not prevent neuronal damage in the lithium-pilocarpine model of epilepsy

Electroconvulsive therapy, which is used to treat refractory major depressi on in humans increases seizure threshold and decreases seizure duration. Mo reover, the expression of brain derived neurotrophic factor induced by elec troshocks (ECS) might protect hippocampal cells from death in patients suff ering from depression. As temporal lobe epilepsy is linked to neuronal dama ge in the hippocampus, we tested the effect of repeated ECS on subsequent s tatus epilepticus (SE) induced by lithium-pilocarpine and leading to cell d eath and temporal epilepsy in the rat. Eleven maximal ECS were applied via ear-clips to adult rats. The last one was applied 2 days before the inducti on of SE by lithium-pilocarpine. The rats were electroencephalographically recorded to study the SE characteristics. The rats treated with ECS before pilocarpine (ECS-pilo) developed partial limbic (score 2) and propagated se izures (score 5) with a longer latency than the rats that underwent SE alon e (sham-pilo). Despite this delay in the initiation and propagation of the seizures, the same number of ECS- and sham-pilo rats developed SE with a si milar characteristic pattern. The expression of c-Fos protein was down-regu lated by repeated ECS in the amygdala and the cortex. In ECS-pilo rats, c-F os expression was decreased in the piriform and entorhinal cortex and incre ased in the hilus of the dentate gyrus. Neuronal damage was identical in th e forebrain areas of both groups, while it was worsened by ECS treatment in the substantia nigra pars reticulata, entorhinal and perirhinal cortices c ompared to sham-pilo rats. Finally, while 11 out of the 12 sham-pilo rats d eveloped spontaneous recurrent seizures after a silent period of 40 +/- 27 days, only two out of the 10 ECS-pilo rats became epileptic, but after a pr olonged latency of 106 and 151 days. One ECS-pilo rat developed electrograp hic infraclinical seizures and seven did not exhibit any seizures. Thus, th e extensive neuronal damage occurring in the entorhinal and perirhinal cort ices of the ECS-pilo rats seems to prevent the establishment of the hyperex citable epileptic circuit. (C) 2000 Elsevier Science B.V. All rights reserv ed.