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.