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Published on: June 11, 2020
Long-term effects of status epilepticus in the immature brain are specific for age and model
Maria Roberta Cilio1, Yoshimi Sogawa, Byung-Ho Cha
1Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital Boston, Boston, Massachusetts, USA. cilio@opbg.net
Insights
Status epilepticus (SE) in developing rats impacts adult cognitive function and hippocampal plasticity differently based on age at insult. SE at P16 and P20, but not P12, caused lasting deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Epilepsy Research
Background:
- Status epilepticus (SE) in children carries significant mortality and morbidity.
- Adult brains show lasting cognitive and memory deficits after SE.
- The developing brain's vulnerability to SE-induced alterations is less understood.
Purpose of the Study:
- To investigate age-dependent long-term effects of SE on hippocampal plasticity and cognitive function.
- To determine if SE consequences during development are specific to age and model.
Main Methods:
- Lithium-pilocarpine (Li-PC) induced SE in rats at postnatal days 12, 16, and 20.
- Spatial memory and seizure susceptibility were assessed in adulthood (P55).
Main Results:
- SE at P12 did not cause detectable adult structural or functional changes.
- SE at P16 and P20 led to hippocampal cell loss and mossy fiber sprouting.
- Adult rats experiencing SE at P16 or P20 exhibited cognitive impairment.
Conclusions:
- The developing brain's response to SE is age-dependent.
- SE during specific developmental windows (P16, P20) results in long-term hippocampal and cognitive deficits.
- While generalized seizure threshold remained unchanged, SE at P20 increased susceptibility to kindling in adulthood.
Purpose:
Status epilepticus (SE) is more common in children than adults and has a high mortality and morbidity rate. SE in adult rats results in long-term disturbances in learning and memory, as well as an enhanced seizure susceptibility to further seizures. In contrast, a number of studies suggest that the immature brain is less vulnerable to the morphologic and physiologic alterations after SE. The goal of this study was to determine whether the long-term consequences of SE during development on hippocampal plasticity and cognitive function are age and model specific.
Methods:
We used lithium-pilocarpine (Li-PC) to induce SE at different age points during development (P12, P16, P20) and evaluated the effects of this abnormal neural activity on spatial memory performance and seizure susceptibility in the animals beginning at P55, corresponding to young adulthood.
Results:
We demonstrated that SE at P12 did not result in any structural or functional changes detectable in adulthood, whereas SE at both P16 and P20 induced cell loss and mossy fiber sprouting within the hippocampus and cognitive impairment when the animals were tested as adults.
Conclusions:
Whereas the seizure threshold to generalized seizures was not altered, animals with SE at P20 showed an increased susceptibility to kindling in adulthood.
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