PMID- 12969262 OWN - NLM STAT- MEDLINE DCOM- 20031112 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 87 IP - 1 DP - 2003 Oct TI - Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting. PG - 147-59 AB - A significant upregulation of neurotrophins particularly brain-derived neurotrophic factor (BDNF) is believed to be involved in the initiation of epileptogenic changes such as the aberrant axonal sprouting and synaptic reorganization in the injured hippocampus. However, it is unknown which of the neurotrophins are upregulated during the peak period of aberrant mossy fiber sprouting in the chronically injured hippocampus. We measured chronic changes in the levels of BDNF, nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the adult hippocampus using enzyme-linked immunosorbent assay (ELISA) after a unilateral intracerebroventricular administration of kainic acid (KA), a model of temporal lobe epilepsy. For comparison, neurotrophins were also measured from the control intact hippocampus. Further, to see the association between changes in neurotrophin levels and the progression of mossy fiber sprouting, chronic changes in the mossy fiber distribution within the dentate supragranular layer (DSGL) were quantified. In the KA-lesioned hippocampus, the neurotrophins BDNF and NGF were upregulated at 4 days post-lesion, in comparison to their levels in the intact hippocampus. However, the concentration of BDNF reached the baseline level at 45 days post-lesion and dramatically diminished at 120 days post-lesion. In contrast, the upregulation of NGF observed at 4 days post-lesion was sustained at both 45 days and 120 days post-lesion. The concentration of NT-3 was upregulated at 45 days post-lesion but remained comparable to baseline levels at 4 days and 120 days post-lesion. Interestingly, analysis of mossy fiber sprouting revealed that most of the aberrant sprouting in the lesioned hippocampus occurs between 45 days and 120 days post-lesion. Taken together, these results suggest that the period of robust mossy fiber sprouting does not correlate with the phase of post-lesion BDNF upregulation. Rather, it shows a relationship with the time of upregulation of neurotrophins NGF and NT-3. FAU - Shetty, Ashok K AU - Shetty AK AD - Medical Research Service, Veterans Affairs Medical Center, Durham, North Carolina, USA. Ashok.Shetty@duke.edu FAU - Zaman, Vandana AU - Zaman V FAU - Shetty, Geetha A AU - Shetty GA LA - eng GR - R01AG20924/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 9061-61-4 (Nerve Growth Factor) RN - SIV03811UC (Kainic Acid) SB - IM MH - Animals MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Disease Models, Animal MH - Disease Progression MH - Epilepsy, Temporal Lobe/chemically induced/*metabolism/pathology MH - Hippocampus/drug effects/*metabolism/pathology MH - Injections, Intraventricular MH - Kainic Acid MH - Male MH - Mossy Fibers, Hippocampal/drug effects/*pathology MH - Nerve Growth Factor/metabolism MH - Nerve Growth Factors/*metabolism MH - Neurotrophin 3/metabolism MH - Rats MH - Rats, Inbred F344 EDAT- 2003/09/13 05:00 MHDA- 2003/11/13 05:00 CRDT- 2003/09/13 05:00 PHST- 2003/09/13 05:00 [pubmed] PHST- 2003/11/13 05:00 [medline] PHST- 2003/09/13 05:00 [entrez] AID - 1979 [pii] AID - 10.1046/j.1471-4159.2003.01979.x [doi] PST - ppublish SO - J Neurochem. 2003 Oct;87(1):147-59. doi: 10.1046/j.1471-4159.2003.01979.x.