Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling

Haas, K. Z., Sperber, E. F., Opanashuk, L. A., Stanton, P. K., Moshe, S. L. (2001) Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling. Hippocampus, 11 (6). pp. 615-625. ISSN 1050-9631

URL: http://www.ncbi.nlm.nih.gov/pubmed/11811655
DOI: 10.1002/hipo.1076

Abstract

Seizures in adult rats result in long-term deficits in learning and memory, as well as an enhanced susceptibility to further seizures. In contrast, fewer lasting changes have been found following seizures in rats younger than 20 days old. This age-dependency could be due to differing amounts of hippocampal neuronal damage produced by seizures at different ages. To determine if there is an early developmental resistance to seizure-induced hippocampal damage, we compared the effects of kainic acid (KA)-induced status epilepticus and amygdala kindling on hippocampal dentate gyrus anatomy and electrophysiology, in immature (16 day old) and adult rats. In adult rats, KA status epilepticus resulted in numerous silver-stained degenerating dentate hilar neurons, pyramidal cells in fields CA1 and CA3, and marked numerical reductions in CA3c pyramidal neuron counts (-57%) in separate rats. Two weeks following the last kindled seizure, some, but significantly less, CA3c pyramidal cell loss was observed (-26%). Both KA status epilepticus and kindling induced mossy-fiber sprouting, as evidenced by ectopic Timm staining in supragranular layers of the dentate gyrus. In hippocampal slices from adult rats, paired-pulse stimulation of perforant path axons revealed a persistent enhancement of dentate granule-cell inhibition following KA status epilepticus or kindling. While seizures induced by KA or kindling in 16-day-old rats were typically more severe than in adults, the immature hippocampus exhibited markedly less KA-induced cell loss (-22%), no kindling-induced loss, no detectable synaptic rearrangement, and no change in dentate inhibition. These results demonstrate that, in immature rats, neither severe KA-induced seizures nor repeated kindled seizures produce the kind of hippocampal damage and changes associated with even less severe seizures in adults. The lesser magnitude of seizure-induced hippocampal alterations in immature rats may explain their greater resistance to long-term effects of seizures on neuronal function, as well as future seizure susceptibility. Conversely, hippocampal neuron loss and altered synaptic physiology in adults may contribute to increased sensitivity to epileptogenic stimuli, spontaneous seizures, and behavioral deficits.

Item Type: Paper
Uncontrolled Keywords: CA1 CA3 kainic acid seizures development epilepsy dentate gyrus PAIRED-PULSE DEPRESSION BRAIN DAMAGE SYNDROME INDUCED SYNAPTIC REORGANIZATION INDUCED NEURONAL INJURY LONG-TERM CONSEQUENCES ACID-INDUCED SEIZURES KAINIC-ACID DENTATE GYRUS RECURRENT SEIZURES DEVELOPING RATS
Subjects: diseases & disorders > nervous system diseases and disorders > epilepsy
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
CSHL Authors:
Communities: CSHL labs > Cline lab
Depositing User: Matt Covey
Date: 2001
Date Deposited: 22 Jan 2014 19:18
Last Modified: 22 Jan 2014 19:18
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29241

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