Upregulation of the neuronal Per‐Arnt‐Sim domain protein 4 (Npas4) in the rat corticolimbic system following focal cerebral ischemia

The neuronal Per‐Arnt‐Sim domain protein 4 (Npas4) is an important transcriptional regulator of synaptic plasticity and cognition. The present study characterises the in vivo neuroanatomical expression pattern of the Npas4 protein in a rat model of focal cerebral ischemia. Animals were subjected to unilateral middle cerebral artery occlusion for 2 h, after which the spatiotemporal and neuronal profiles of Npas4 protein expression were analysed by immunohistochemistry at different time points post‐reperfusion. Focal cerebral ischemia induced an early, transient and robust upregulation of Npas4 in a brain region‐dependent manner involving predominantly principal neurons. Interestingly, we observed a unique differential induction of Npas4 protein expression in corticolimbic regions of the rat brain that are critically linked to cognition and emotion. These findings suggest that stroke‐induced Npas4 upregulation may be involved in a transcriptional regulatory program within the corticolimbic circuitry following an ischemic insult.