Effects of second generation tetracyclines on penicillin-epilepsy-induced hippocampal neuronal loss and motor incoordination in rats.

Epileptic seizures cause pathological changes such as sclerosis and pyramidal neuronal loss in the hippocampus. Experimentally, epilepsy can be induced by application of various chemicals directly to the cerebral cortex. In this study, epilepsy was induced in rats by intracortical application of 500 IU penicillin G, and the effect of minocycline and doxycycline on the resulting motor incoordination (rotarod) and hippocampal neuronal loss in CA1, CA2 and CA3 fields (optical fractionator method) were investigated. The rotarod performance was reduced in the epilepsy group to 285.1+/-6.9 s (P<0.05 vs. sham-300 s). Minocycline and doxycycline increased this performance to 297.4+/-1.0 s and 296.9+/-1.2 s respectively. No significant difference was detected between minocycline and doxycycline. The present results also showed that the number of neurons (x10(3)) in the sham group was 150+/-9. In the penicillin-epileptic rats, the number was decreased to 105+/-7 (P<0.01). Minocycline, but not doxycycline (125+/-8), significantly increased the number to 131+/-3 (P<0.05). In conclusion, the second generation tetracycline minocycline decreased the loss of hippocampal neurons and motor incoordination in penicillin-epileptic rats. Minocycline could protect against a variety of neurological insults including epilepsy.