Increased cortical expression of the orexin-1 receptor following permanent middle cerebral artery occlusion in the rat

The orexins (hypocretins) have recently been implicated in neurodegeneration associated with narcolepsy. Therefore, the current study was designed to investigate changes in the expression of prepro-orexin and the orexin receptors, OX 1R and OX 2R following permanent middle cerebral artery occlusion (MCAO) in the rat. Six and twenty-four hours following MCAO, increased OX 1R mRNA and protein expression (as assessed by Western blotting and immunohistochemistry) was detected in the ischaemic cortex compared with control tissue. In contrast, however, no increase in OX 2R mRNA was detected at any time-point and prepro-orexin levels in the cortex were below assay detection levels. This study shows that orexin receptor localization is altered following cerebral ischaemia. The development of selective orexin receptor antagonists will be crucial in establishing a role for this family of novel peptides in the mechanisms underlying ischaemic cell death.