Inflammation contributes to seizure-induced hippocampal injury in the neonatal rat brain

Abstract

The extent of neuronal injury in the hippocampus produced by experimental status epilepticus (SE) is age dependent and is not readily demonstrable in many models of neonatal seizures. Neonatal seizures often occur in clinical settings that include an inflammatory component. We examined the potential contributory role of pre-existing inflammation as an important variable in mediating neuronal injury. Postnatal day 7 (P7) and P14 rat pups were injected with lipopolysaccharide (LPS), 2 h prior to SE induced by lithium-pilocarpine (LiPC). Neuronal injury was assessed by well-described histologic methods. While LPS by itself did not produce any discernible cell injury at either age, this treatment exacerbated hippocampal damage induced by LiPC-SE. The effect was highly selective for the CA1 subfield. Inflammation can contribute substantially to the vulnerability of immature hippocampus to seizure-induced neuronal injury. The combined effects of inflammation and prolonged seizures in early life may impact long-term outcomes of neonatal seizures.