Increased Seizure Susceptibility and Up-regulation of nNOS Expression in Hippocampus Following Recurrent Early-life Seizures in Rats

다국어 초록 (Multilingual Abstract)

This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 or 50 using the flurothyl method.
Changes in nNOS expression were determined by quantitative immunoblotting on day 50. On average, rats had 8.4±2.7 seizures during 10 daily 1 hr behavioral monitoring sessions. As adults (days 50-60), all rats displayed interictal spikes in the hippocampus and/or overlying cortex. Brief electrographic seizures were recorded in only one of five animals. Rats appeared to progress from a period of marked seizure susceptibility (day 22) to one of lessened seizure susceptibility (day 50). Up-regulation of nNOS expression following early-life recurrent seizures was observed on day 50. In conclusion, these data suggested that recurrent early-life seizures had the long-term effects on seizure susceptibility late in life and up-regulatory nNOS expression on the hippocampus during brain development, and nNOS appeared to contribute to the persistent changes in seizure susceptibility, and epileptogenesis.

참고문헌 (Reference)

1 Lee CL, "Tetanus toxin-induced seizures in infant rats and their effects on hippocampal excitability in adulthood" 17 : 97-109, 1995

2 Albus U, "Tetanus toxin inhibits the evoked outflow of inhibitory (GABA) and excitatory (o-aspartate) amino acid from particulate brain cortex" 21 : 97-110, 1983

3 Haut SR, "Susceptibility of immature and adult brains to seizure effects" 3 : 608-617, 2004

4 Swann JW, "Spine loss and other dendritic abnormalities in epilepsy" 10 : 617-625, 2000

5 Baram TZ, "Short interval amygdale kindling in neonatal rats" 73 : 79-83, 1993

6 Lee CL, "Seizures produced in neonatal rats by stereotaxic injections of tetanus toxin (TT): in vivo and in vitro models of seizures in early infancy" 34 : 59-, 1993

7 Elmér E, "Regulation of neuronal nitric oxide synthase mRNA levels in rat brain by seizure activity" 7 : 1335-1339, 1996

8 Jefferys JG, "Physiological and behavioral consequences of seizures induced in the rat by intrahippocampal tetanus toxin" 110 : 517-532, 1987

9 Sunico CR, "Nitricoxide- directed synaptic remodeling in the adult mammal CNS" 25 : 1448-1458, 2005

10 Roskams AJ, "Nitric oxide mediates the formation of synaptic connections in developing and regenerating olfactory receptor neurons" 13 : 289-299, 1994

11 Holmes GL, "New concepts in neonatal seizures" 21 : 3-8, 2002

12 Tremblay E, "Maturation of kainic acid seizure-brain damage syndrome in the rat. I" 13 : 1051-1072, 1984

13 Smith KL, "Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy" 79 : 106-116, 1998

14 Hawkins CA, "Limbic epilepsy induced by tetanus toxin: a longitudinal electroencephalographic study" 28 : 431-444, 1987

15 Moshé SL, "Kindling in developing rats: persistence of seizures into adulthood" 256 : 67-71, 1982

16 Haas KZ, "Kindling in developing animals: expression of severe seizures and enhanced development of bilateral foci" 56 : 275-280, 1990

17 Cavalheiro EA, "Intracortical and intrahippocampal injections of kainic acid in developing rats: an electrographic study" 56 : 480-486, 1983

18 Endoh M, "Expression of the neural form of nitric oxide synthase by CA1 hippocampal neurons and other central nervous system neurons" 63 : 679-689, 1994

19 Mellanby J, "Epileptiform syndrome in rats produced by injecting tetanus toxin into the hippocampus" 40 : 404-414, 1977

20 Holmes GL, "Epilepsy in the developing brain: lessons from the laboratory and clinic" 38 : 12-30, 1997

21 Cha BH, "Effect of topiramate following recurrent and prolonged seizures during early development" 51 : 217-232, 2002

22 Williamson LC, "Differential effects of tetanus toxin on inhibitory and excitatory neurotransmitter release from mammalian spinal cord cells in culture" 59 : 2148-2157, 1992

23 Swann JW, "Developmental neuroplasticity: roles in early life seizures and chronic epilepsy" 79 : 203-216, 1999

24 Ohyu J, "Developmental characteristics of neuronal nitric oxide synthase (nNOS) immunoreactive neurons in fetal to adolescent human brains" 110 : 193-202, 1998

25 Bonthius DJ, "Deficiency of neuronal nitric oxide synthase (nNOS) worsens alcohol-induced microencephaly and neuronal loss in developing mice" 138 : 45-59, 2002

26 Jefferys JG, "Chronic epileptic foci in vitro in hippocampal slices from rats with tetanus toxin epileptic syndrome" 62 : 458-468, 1989

27 Swann JW, "Cellular abnormalities and synaptic plasticity in seizure disorders of the immature nervous system" 6 : 258-267, 2000

28 Michelson HB, "An ontogenetic study of kindling using rapidly recurring hippocampal seizures" 61 : 79-85, 1991

29 Jensen FE, "Acute and chronic effects of seizures in the developing brain: experimental models" 40 (40): 51-58, 1999

30 Dawson TM, "A novel neuronal messenger molecule in the brain: the free radical, nitric oxide" 32 : 297-311, 1992