Ibotenate injections into the pre- and parasubiculum provide partial protection against kainate-induced epileptic damage in layer III of rat entorhinal cortex.
OBJECTIVE
A loss of neurons in layer III of the entorhinal cortex (EC) is often observed in patients with temporal lobe epilepsy and in animal models of the disorder. We hypothesized that the susceptibility of layer III of the EC to prolonged seizure activity might be mediated by excitatory afferents originating in the presubiculum.


METHODS
Experiments were designed to ablate the presubiculum unilaterally by focal ibotenate injections and to evaluate the effect of this deafferentation on the vulnerability of EC layer III neurons to the chemoconvulsant kainate (injected systemically 5 days later).


RESULTS
After treatment with kainate, 11 of the 15 rats preinjected with ibotenate showed clear-cut, partial neuroprotection in layer III of the EC ipsilateral to the ibotenate lesion. Serial reconstruction of the ibotenate-induced primary lesion revealed that entorhinal neurons were protected only in animals that had lesions in the pre- and parasubiculum, especially in the deep layers (IV-VI).


CONCLUSIONS
The deep layers of the pre- and parasubiculum appear to control the seizure-induced damage of EC layer III. This phenomenon may be of relevance for epileptogenesis and for the pathogenesis of temporal lobe epilepsy.
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Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA.
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Schwarcz
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D000818:Animals; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects* / Q000502:physiology*; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology* / Q000517:prevention & control; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D007051:Ibotenic Acid; D007608:Kainic Acid