Neurogenesis and epilepsy in the developing brain

SummaryMultiple studies have highlighted how seizures induce different molecular, cellular, and physiologic consequences in an immature brain as compared to a mature brain. In keeping with these studies, seizures early in life alter dentate granule cell birth in different, and even opposing, fashion to adult seizure models (seeTable 1). During the first week of rodent postnatal life, seizures decrease cell birth in the postictal period, but do not alter the maturation of newborn cells. Seizures during the second week of life have varied effects on dentate granule cell birth, either causing no change or increasing birth, and may promote a mild increase in neuronal survival. During the third and fourth weeks of life, seizures begin to increase cell birth similar to that seen in adult seizure models. Interestingly, animals that experienced seizure during the first month of life have an increase in cell birth during adulthood, opposite to the reported decrease in chronic animals experiencing a prolonged seizure as an adult. Children have more ongoing cell birth in the dentate gyrus than adults, and markers of cell division are further increased in children with refractory temporal lobe epilepsy. There are clear age‐dependent differences in how seizures alter cell birth in the dentate gyrus both acutely and chronically. Future studies need to focus on how these changes in neurogenesis influence dentate gyrus function and what they imply for epileptogenesis and learning and memory impairments, so commonly found in children with temporal lobe epilepsy.1Early seizures alter cell birth in rodent dentate gyrusAge Seizure model Acute and subacute changes in cell birth Chronic changes in cell birth1st week of life Flurothyl Increased ictal a and decreased postictal b ND Pilocarpine Decreased postictal c Increased cKainate Decreased d ND 2nd week of life Pilocarpine Increased e ND Kainate Increased f ND Hyperthermia No change f,g Slight increase in newborn cell survival g (female only) 3rd –4th week of life Pilocarpine Increased e,h Increased in those animals that develop spontaneous seizures jKainate Increased i (similar to adults) NDND, not determined.aHolmes et al., 2008; b McCabe et al., 2001; c Xiu‐Yu et al., 2007; d Liu et al., 2003; e Sankar et al., 2000; f Bender et al., 2003; g Lemmens et al., 2005; h Porter et al., 2004; i Gray et al., 2002; j Cha et al., 2004.