PMID- 11718838
DA - 20011123
DCOM- 20020204
IS - 0165-3806
VI - 131
IP - 1-2
DP - 2001 Nov 26
TI - Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus.
PG - 73-83 AB - Neonatal seizures are frequently associated with cognitive impairment and reduced seizure threshold. Previous studies in our laboratory have demonstrated that rats with recurrent neonatal seizures have impaired learning, lower seizure thresholds, and sprouting of mossy fibers in CA3 and the supragranular region of the dentate gyrus in the hippocampus when studied as adults. The goal of this study was to determine the age of onset of cognitive dysfunction and alterations in seizure susceptibility in rats subjected to recurrent neonatal seizures and the relation of this cognitive impairment to mossy fiber sprouting and expression of glutamate receptors. Starting at postnatal day (P) 0, rats were exposed to 45 flurothyl-induced seizures over a 9-day period of time. Visual-spatial learning in the water maze and seizure susceptibility were assessed in subsets of the rats at P20 or P35. Brains were evaluated for cell loss, mossy fiber distribution, and AMPA (GluR1) and NMDA (NMDAR1) subreceptor expression at these same time points. Rats with neonatal seizures showed significant impairment in the performance of the water maze and increased seizure susceptibility at both P20 and P35. Sprouting of mossy fibers into the CA3 and supragranular region of the dentate gyrus was seen at both P20 and P35. GluR1 expression was increased in CA3 at P20 and NMDAR1 was increased in expression in CA3 and the supragranular region of the dentate gyrus at P35. Our findings indicate that altered seizure susceptibility and cognitive impairment occurs prior to weaning following a series of neonatal seizures. Furthermore, these alterations in cognition and seizure susceptibility are paralleled by sprouting of mossy fibers and increased expression of glutamate receptors. To be effective, our results suggest that strategies to alter the adverse outcome following neonatal seizures will have to be initiated during, or shortly following, the seizures.
AD - Department of Neurology, Harvard Medical School, Clinical Neurophysiology
Laboratory - Hunnewell 2, Children's Hospital, 300 Longwood Avenue,
Boston, MA 02115, USA.
FAU - Sogawa, Y
AU - Sogawa Y
FAU - Monokoshi, M
AU - Monokoshi M
FAU - Silveira, D C
AU - Silveira DC
FAU - Cha, B H
AU - Cha BH
FAU - Cilio, M R
AU - Cilio MR
FAU - McCabe, B K
AU - McCabe BK
FAU - Liu, X
AU - Liu X
FAU - Hu, Y
AU - Hu Y
FAU - Holmes, G L
AU - Holmes GL
LA - eng
ID - 2P30 HD 18655/HD/NICHD
ID - NS 27984/NS/NINDS
PT - Journal Article
CY - Netherlands
TA - Brain Res Dev Brain Res
JID - 8908639
RN - 0 (Antibodies)
RN - 0 (Convulsants)
RN - 0 (GluR1 protein)
RN - 0 (NMDA receptor A1)
RN - 0 (Receptors, AMPA)
RN - 0 (Receptors, N-Methyl-D-Aspartate)
RN - 333-36-8 (Flurothyl)
SB - IM
MH - Animal
MH - Animals, Newborn
MH - Antibodies
MH - Cognition Disorders/*pathology
MH - Convulsants
MH - Epilepsy/chemically induced/*pathology
MH - Flurothyl
MH - Immunoenzyme Techniques
MH - Male
MH - Maze Learning
MH - Memory
MH - Mossy Fibers, Hippocampal/chemistry/*pathology
MH - Rats
MH - Rats, Sprague-Dawley
MH - Receptors, AMPA/analysis/immunology
MH - Receptors, N-Methyl-D-Aspartate/analysis/immunology
MH - Staining and Labeling
MH - Support, Non-U.S. Gov't
MH - Support, U.S. Gov't, P.H.S.
EDAT- 2001/11/24 10:00
MHDA- 2001/11/24 10:00
AID - S0165380601002656 [pii]
PST - ppublish
SO - Brain Res Dev Brain Res 2001 Nov 26;131(1-2):73-83.