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New concepts in neonatal seizures
Gregory L Holmes1, Roustem Khazipov, Yehezkiel Ben-Ari
1Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital, Boston, MA 02115, USA.
Insights
Neonatal seizures, often thought benign, injure the developing brain. Immature brains are prone to seizures due to excitatory/inhibitory imbalances, leading to functional deficits and altered brain development.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Epilepsy Research
Background:
- The immature brain exhibits a higher susceptibility to seizures compared to the mature brain.
- This increased propensity is attributed to an imbalance between excitatory and inhibitory neural inputs.
- Specific factors include the depolarizing effect of GABA(A) and delayed GABA(B) inhibition in early life, alongside overexpressed glutamatergic synapses.
Purpose of the Study:
- To investigate the impact and consequences of seizures on the developing brain.
- To determine if neonatal seizures are indeed benign events or if they cause lasting injury.
- To characterize the age-related patterns of seizure-induced brain injury.
Main Methods:
- The study likely involved preclinical models (rodents) to examine brain activity and responses to seizures during early developmental stages.
- Analysis of neurochemical and synaptic changes post-seizure.
- Assessment of cognitive functions, such as visual-spatial memory, and seizure thresholds.
Main Results:
- While the immature brain shows resistance to acute cell death from seizures, functional abnormalities are evident.
- Seizures in neonates lead to impaired visual-spatial memory and a reduced seizure threshold.
- Neonatal seizures trigger activity-dependent developmental changes, including altered synaptogenesis and reduced neurogenesis.
Conclusions:
- Neonatal seizures are not benign and can cause significant, age-related injury to the developing brain.
- The findings challenge the long-held view of neonatal seizures as inconsequential events.
- Understanding these effects is crucial for managing and treating epilepsy in infants and children.
Abstract:
The immature brain is more prone to seizures than the older brain as a result of an imbalance between excitatory and inhibitory input. The depolarizing, rather than hyperpolarizing effect of GABA(A) during the first week of life in the rodent, and the delay in postsynaptic GABA(B) inhibition coupled with the over-expression of glutamatergic synapses contribute to this increased propensity toward seizures. It is now clear that seizures can be injurious to the immature brain, although the pattern of seizure-induced injury is age-related. While the immature brain is resistant to acute seizure-induced cell loss, there are functional abnormalities following seizures with impairment of visual-spatial memory and reduced seizure threshold. Neonatal seizures are also associated with a number of activity-dependent changes in brain development including altered synaptogenesis and reduction in neurogenesis. These results argue that neonatal seizures should no longer be considered as benign events.