Rat Neonatal Immune Challenge Alters Adult Responses to Cerebral Ischaemia

Abstract

Infection, inflammation, and hyperthermia associated with cerebral ischaemia are known to contribute to enhanced neuronal cell loss and more severe behavioural deficits. Because neonatal exposure to an immune challenge has been shown to alter the severity of inflammatory and febrile responses to a further immune challenge experienced in adulthood, we hypothesised that this could also alter temperature responses and neuronal survival after ischaemia. Thus, male Sprague–Dawley rats were treated at postnatal day 14 with a single injection of the bacterial endotoxin lipopolysaccharide (LPS) and were examined as adults for temperature changes, behavioural deficits, and neuronal cell loss associated with global cerebral ischaemia after a two-vessel occlusion (2 VO). Neonatally LPS-treated rats showed behavioural differences in a novel object exploration paradigm, as well as altered temperature responses to the 2 VO compared with neonatally salinetreated controls. Interestingly, these neonatally LPS-treated rats also showed increased cell loss in the central nucleus of the amygdala, a region that is important in the processing of emotional responses, but that is not usually examined in animal models of cerebral ischaemia. No differences were seen in the CA1, CA3, or dentate gyrus regions of the hippocampus. This work shows the importance of examining brain regions other than the hippocampus in association with global ischaemia. We also highlight the importance of the early period of development in programming an animal's ability to deal with injury such as cerebral ischaemia in adulthood.