The first two authors contributed equally to this work.
Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy
Article first published online: 21 FEB 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 83, Issue 6, pages 1088–1105, 1 May 2006
How to Cite
Rao, M. S., Hattiangady, B., Reddy, D. S. and Shetty, A. K. (2006), Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy. J. Neurosci. Res., 83: 1088–1105. doi: 10.1002/jnr.20802
- Issue published online: 11 APR 2006
- Article first published online: 21 FEB 2006
- Manuscript Accepted: 3 JAN 2006
- Manuscript Revised: 2 JAN 2006
- Manuscript Received: 4 OCT 2005
- National Institute of Neurological Disorders and Stroke. Grant Number: RO1 NS 043507
- Department of Veterans Affairs
- temporal lobe epilepsy;
- hippocampal neurodegeneration;
- spontaneous seizures;
- mossy fiber sprouting
The links among the extent of hippocampal neurodegeneration, the frequency of spontaneous recurrent motor seizures (SRMS), and the degree of aberrant mossy fiber sprouting (MFS) in temporal lobe epilepsy (TLE) are a subject of contention because of variable findings in different animal models and human studies. To understand these issues further, we quantified these parameters at 3–5 months after graded injections of low doses of kainic acid (KA) in adult F344 rats. KA was administered every 1 hr for 4 hr, for a cumulative dose of 10.5 mg/kg bw, to induce continuous stages III–V motor seizures for >3 hr. At 4 days post-KA, the majority of rats (77%) exhibited moderate bilateral neurodegeneration in different regions of the hippocampus; however, 23% of rats exhibited massive neurodegeneration in all hippocampal regions. All KA-treated rats displayed robust SRMS at 3 months post-KA, and the severity of SRMS increased over time. Analyses of surviving neurons at 5 months post-KA revealed two subgroups of rats, one with moderate hippocampal injury (HI; 55% of rats) and another with widespread HI (45%). Rats with widespread HI exhibited greater loss of CA3 pyramidal neurons and robust aberrant MFS than rats with moderate HI. However, the frequency of SRMS (∼3/hr) was comparable between rats with moderate and widespread HI. Thus, in comparison with TLE model using Sprague-Dawley rats (Hellier et al.  Epilepsy Res. 31:73–84), a much lower cumulative dose of KA leads to robust chronic epilepsy in F344 rats. Furthermore, the occurrence of SRMS in this model is always associated with considerable bilateral hippocampal neurodegeneration and aberrant MFS. However, more extensive hippocampal CA3 cell loss and aberrant MFS do not appear to increase the frequency of SRMS. Because most of the features are consistent with mesial TLE in humans, the F344 model appears ideal for testing the efficacy of potential treatment strategies for mesial TLE. © 2006 Wiley-Liss, Inc.