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Pentylenetetrazol-induced recurrent seizures in rat pups: time course on spatial learning and long-term effects
Li-Tung Huang1, San Nan Yang, Chia-Wei Liou
1Department of Pediatrics, Chang Gung Memorial Hospital, Kaohsiung, Tainan, Taiwan. Huang_li@taiwan.com
Insights
Recurrent neonatal seizures, induced by pentylenetetrazol (PTZ), caused long-term spatial memory deficits in rats, even without observable brain cell loss. These cognitive impairments were evident during adolescence.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Epilepsy Research
Background:
- Infant seizures are linked to neurocognitive deficits.
- Immature brains may be less vulnerable to seizure injury than adult brains.
- This study investigates long-term effects of early-life seizures on cognitive function.
Purpose of the Study:
- To determine the long-term effects of recurrent neonatal seizures on cognitive tasks in adolescence and adulthood.
- To assess if early-life seizures impact spatial memory, motor performance, and activity levels.
- To examine potential morphologic changes in the hippocampus following seizures.
Main Methods:
- Neonatal rats received daily pentylenetetrazol (PTZ) injections from postnatal day 10.
- Spatial memory was assessed using the Morris water maze at postnatal days 35 and 60.
- Motor function, activity levels, seizure threshold, and hippocampal histology were evaluated.
Main Results:
- PTZ-treated rats exhibited significant spatial memory deficits at both tested ages.
- No differences were observed in seizure threshold, motor balance, or activity levels.
- Histology revealed increased Timm staining in the CA3 subfield, but no cell loss.
Conclusions:
- Recurrent PTZ-induced seizures lead to lasting cognitive deficits in the developing brain.
- Morphologic changes, specifically in the CA3 region, correlate with cognitive impairments.
- These deficits are detectable as early as pubescence, highlighting the vulnerability of the developing brain.
Purpose:
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.