ANOXIA DURING KAINATE STATUS EPILEPTICUS SHORTENS BEHAVIORAL CONVULSIONS BUT GENERATES HIPPOCAMPAL NEURON LOSS AND SUPRAGRANULAR MOSSY FIBER SPROUTING

In rats, this study determined the impact of systemic hypoxia during l ate kainate-induced status epilepticus on hippocampal neuron loss and mossy fiber sprouting. Non-fasted Sprague-Dawley rats were prepared as follows: Naive controls (n = 5); rats placed 2 min in a hypoxia chamb er (hypoxia only; n = 6); rats that seized for more than 6 h from kain ic acid (KA-status; 12 mg/kg; i.p.; n = 7); and another KA-status grou p placed into the hypoxia chamber 75 min after the convulsions started (KA-status/hypoxia n=16). All rats, except for half of the KA-status/ hypoxia animals, were perfused 2 weeks later (short-term). The other 8 KA-status/hypoxia rats were perfused after 2 months (long-term). Hipp ocampal sections were studied for neuron densities and aberrant mossy fiber sprouting at three ventral to dorsal levels. Fascia dentata (FD) mossy fiber sprouting was quantified as an increase in the inner minu s outer molecular layer (IML-OML) gray value (GV) difference. Behavior ally, KA-status/hypoxia rats had a shorter duration of convulsive stat us epilepticus than KA-status animals without anoxia. Hippocampal sect ions showed that compared to controls: (1) hypoxia-only rats showed no differences in ventral neuron densities and neo-Timm's stained IML-OM L GVs; (2) KA-status rats had decreased CA3 densities and a non-signif icant increase in ventral IML-OML GV differences; and (3) KA-status/hy poxia short-term animals showed decreased hilar, CA3 and CA1 densities and increased ventral IML-OML GV differences. Compared to KA-status/h ypoxia shortterm rats, long-term animals showed no differences in vent ral hippocampal neuron densities, but middle and dorsal sections demon strated increased IML-OML GV differences and animals were observed to have spontaneous limbic epilepsy. These results indicate that rats exp osed to kainate-induced status epilepticus for over 1 h and then a hyp oxic insult had a shorter duration of convulsive status, decreased hip pocampal neuron densities and greater FD mossy fiber sprouting than co ntrols and the amount of neuronal damage and sprouting was slightly mo re than animals subjected to 6 h of kainate-induced status. This suppo rts the hypothesis that a physiologic insult during status can shorten the convulsive episode, but still produce hippocampal pathology with a number of clinical and pathologic similarities to human mesial tempo ral lobe epilepsy (MTLE). (C) 1998 Elsevier Science B.V. All rights re served.