engleski

Npas4 is up-regulated in the corticolimbic system of the rodent brain following focal cerebral ischaemia

The aim of this study was to use immunohistochemistry to investigate the expression of the neural activity-dependent transcription factor Neuronal PAS domain protein 4 (Npas4) in two different rodent models of stroke ; middle cerebral artery occlusion in rats and Rose Bengalmediated photochemical ischaemia in mice. Despite the differences in the size and location of the infarcts produced by these two models, the pattern of Npas4 expression was remarkably similar across both paradigms. Npas4 was found to be rapidly, robustly and transiently upregulated in the ipsilateral hemisphere following cerebral ischaemia. No expression was observed in the infarct core or the contralateral hemisphere. In both models the same characteristic pattern of Npas4 expression was observed in discrete corticolimbic regions which included sites that were undamaged and were some distance away from the lesion. Highest expression was seen in the frontal and piriform cortices, nucleus accumbens, ventral pallidum, amygdala, thalamus and hypothalamus. This study demonstrates that: (1) following cerebral ischaemia there is a unique induction of Npas4 expression in corticolimbic regions of the rodent brain that are linked to cognition and emotion, and (2) this distinctive pattern of expression is reproduced in two distinct models of stroke that differ vastly in the size and location of the resulting infarct. We hypothesise that Npas4 is part of a transcriptional programme that becomes activated specifically within the corticolimbic circuitry following an ischemic insult and that this aberrant expression is linked to the cognitive and emotional dysfunction associated with ischaemic insult to the brain.

Npas4 ; cerebral ischaemia ; rodent ; middle cerebral artery occlusion, photochemical stroke

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