Fine Mapping of the Spatial Relationship between Acute Ischemia and Dendritic Structure Indicates Selective Vulnerability of Layer V Neuron Dendritic Tufts within Single Neurons in Vivo

Abstract

We have evaluated the spatial relationship between clotted vasculature and the structural integrity of layer V cortical neurons in YFP (yellow fluorescent protein)-H transgenic mice 2 to 10 h after photothrombotic stroke. Fortuitously, ischemic zones could be finely mapped about dysmorphic YFP labeled axons and dendrites using histology since texas-red dextran used to assess blood flow in vivo was trapped within fixed clotted vessels. Ischemic damage to layer V neurons located at the border of ischemia was contained within apical tuft spiny dendritic structures and did not propagate to spines on the more proximal region of the apical dendrite. The lateral spread of dendritic damage decayed sharply with distance from the edge of ischemia (50% reduction in beaded dendrites within ~ 100 μm) and increased with time up to 6 h after stroke but not thereafter. Axonal damage also increased with time but extended further laterally than dendritic damage, up to 500 μm from the stroke core. Apoptotic and necrotic cell death cascades were activated 6 h after stroke; however, only within 300 μm of the ischemic core. These data suggest that the axonal and dendritic circuitry of neurons located 300 μm outside of an ischemic zone can be relatively free of damage or commitment to cell death suggesting that they may be in an ideal position to contribute to functional recovery. Given that ischemic damage may have a larger effect on circuitry involving superficial dendrites and projecting axons, it is conceivable that surviving peri-infarct neurons may have unique structural and functional properties.