α2-Adrenoceptors do not mediate neuroprotection in acute ischemic stroke in mice

We assessed the neuroprotective potential of alpha(2)-adrenoceptors in ischemic stroke using mice with targeted deletions of individual alpha(2)-adrenoceptor subtypes (alpha(2A) (-/-), alpha(2B) (-/-), alpha(2C) (-/-), alpha(2A/C) (-/-)). The effects of the alpha(2)-adrenoceptor agonist clonidine were studied in parallel. Focal cerebral ischemia was induced with or without clonidine pretreatment by transient middle cerebral artery occlusion. Neurologic outcome and infarct volumes were evaluated on day 1. Cerebral blood flow (CBF) and mean arterial pressure were determined. alpha(2)-Adrenoceptor null mice did not display larger infarct volumes compared with wild-type (WT) mice under basal conditions (P > 0.05). In line with this finding, pretreatment with clonidine did not protect from ischemic brain damage in WT mice or alpha(2A) (-/-), alpha(2B) (-/-), and alpha(2C) (-/-) mice. Clonidine induced smaller infarct volumes only in alpha(2A/C) (-/-) mice (P < 0.05), but this did not translate into improved neurologic function (P > 0.05). Importantly, while clonidine caused a significant decrease in arterial blood pressure in all groups, it had no blood pressure lowering effect in alpha(2A/C) (-/-) mice, and this correlated with higher CBF and smaller infarct volumes in this group. In summary, we could not demonstrate a neuroprotective function of alpha(2-)adrenoceptors in focal cerebral ischemia. Careful controlling of physiological parameters relevant for stroke outcome is recommended in experimental stroke studies. Journal of Cerebral Blood Flow & Metabolism (2011) 31; doi:10.1038/jcbfm.2011.110; published online 27 July 2011