Pentylenetetrazol-induced recurrent seizures in rat pups: time course on spatial learning and long-term effects.
OBJECTIVE
Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood.


METHODS
Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus.


RESULTS
PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone.


CONCLUSIONS
Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence.
Huang
Li-Tung
LT
Department of Pediatrics, Chang Gung Memorial Hospital, Kaohsiung, Tainan, Taiwan. Huang_li@taiwan.com
Yang
San Nan
SN
Liou
Chia-Wei
CW
Hung
Pi-Lien
PL
Lai
Ming-Chi
MC
Wang
Chih-Lu
CL
Wang
Tzu-Jou
TJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count / Q000706:statistics & numerical data; D005106:Exploratory Behavior / Q000502:physiology; D005481:Flurothyl / Q000494:pharmacology; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000473:pathology; D051381:Rats; D012008:Recurrence; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D013037:Spatial Behavior / Q000502:physiology*; D013997:Time Factors
D005481:Flurothyl