Connexin 36 promotes cortical spreading depolarization and ischemic brain damage

Cortical spreading depolarization (CSD) promotes the progression of neuronal injury after cerebral ischemia. However, the mechanisms of propagation of postischemic CSD events are still unclear. In this study we characterized the role of the main neuronal gap junction protein connexin 36 (Cx36) in generating postischemic CSDs. In Cx36-deficient mice and controls we occluded the distal middle cerebral artery. To detect CSD events we recorded the direct current and laser Doppler flow. In addition, locomotor function and the infarct size were determined. Cx36-deficient mice had significantly fewer and shorter CSD events than wild-type controls. Additionally, Cx36 deletion is neuroprotective, leading to a better functional outcome and decreased infarct size after ischemia. These results suggest a detrimental role for Cx36 after ischemia, possibly by promoting CSD. (C) 2012 Elsevier B.V. All rights reserved.