Anoxia during kainate status epilepticus shortens behavioral convulsions but generates hippocampal neuron loss and supragranular mossy fiber sprouting

Mathern, Gary W; Price, Greg; Rosales, Carlos; Pretorius, James K; Lozada, Alana; Mendoza, Delia

« Previous Next »Epilepsy Research
Volume 30, Issue 2 , Pages 133-151, April 1998

Anoxia during kainate status epilepticus shortens behavioral convulsions but generates hippocampal neuron loss and supragranular mossy fiber sprouting

Gary W Mathern
- Division of Neurosurgery, Reed Neurological Research Center, UCLA Medical Center, Los Angeles, CA 90095-1769, USA
- The Brain Research Institute, The University of California, Los Angeles, CA, USA
- The Mental Retardation Research Center, The University of California, Los Angeles, CA, USA
- Corresponding author. Tel.: +1 310 2068777; fax: +1 310 2068461; e-mail: gmathern@ucla.edu
Greg Price
- Department of Neurology, The University of California, Los Angeles, CA, USA
Carlos Rosales
- Department of Neurology, The University of California, Los Angeles, CA, USA
- The Brain Research Institute, The University of California, Los Angeles, CA, USA
James K Pretorius
- The Brain Research Institute, The University of California, Los Angeles, CA, USA
Alana Lozada
- The Brain Research Institute, The University of California, Los Angeles, CA, USA
Delia Mendoza
- The Brain Research Institute, The University of California, Los Angeles, CA, USA

Received 9 January 1997; received in revised form 13 November 1997; accepted 4 December 1997.

Abstract

In rats, this study determined the impact of systemic hypoxia during late 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 chamber (hypoxia only; n=6); rats that seized for more than 6 h from kainic acid (KA-status; 12 mg/kg; i.p.; n=7); and another KA-status group 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). Hippocampal 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 minus outer molecular layer (IML-OML) gray value (GV) difference. Behaviorally, KA-status/hypoxia rats had a shorter duration of convulsive status epilepticus than KA-status animals without anoxia. Hippocampal sections showed that compared to controls: (1) hypoxia-only rats showed no differences in ventral neuron densities and neo-Timm's stained IML-OML GVs; (2) KA-status rats had decreased CA3 densities and a non-significant increase in ventral IML-OML GV differences; and (3) KA-status/hypoxia short-term animals showed decreased hilar, CA3 and CA1 densities and increased ventral IML-OML GV differences. Compared to KA-status/hypoxia short-term rats, long-term animals showed no differences in ventral hippocampal neuron densities, but middle and dorsal sections demonstrated increased IML-OML GV differences and animals were observed to have spontaneous limbic epilepsy. These results indicate that rats exposed to kainate-induced status epilepticus for over 1 h and then a hypoxic insult had a shorter duration of convulsive status, decreased hippocampal neuron densities and greater FD mossy fiber sprouting than controls and the amount of neuronal damage and sprouting was slightly more than animals subjected to 6 h of kainate-induced status. This supports 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 temporal lobe epilepsy (MTLE).

Keywords: Synaptic reorganization, Excitotoxicity, Epilepsy, NIH image