Actin Reorganization Is A Rapid And Reversible Adaptive Response By Neurons Exposed To Ischemic And Excitotoxic Injury In Vitro And In Vivo

In initial stages of ischemic injury, glutamate receptor hyperactivation mediates extensive neuronal cell death. Most of this initial death is due to cytotoxic edema, whereby sodium and chloride entry cause cell swelling. Early subcellular responses to neuronal edema are poorly understood. We observed that actin filaments (F-actin) undergo a dramatic reorganization within the somatodendritic domain of neurons exposed to ischemia and/or sublethal excitotoxicity in vivo and in vitro. Fluorescence imaging was performed on embryonic rat hippocampal neurons cultured for 21-days in vitro. “Ministrokes” were induced in vivo by photothrombosis of a single penetrating vessel in mouse sensorimotor cortex. Animals were fixed 4 or 6 hours after vessel occlusion. Fluorescence images were analyzed in infarct, peri-infarct, and contralateral regions. All experiments were repeated 3-4 times, and quantified in a blinded fashion In control tissue F-actin is concentrated within dendritic spines, with little F-actin in the d...