Role of ionotropic glutamate receptors in ischemic injury and dendritic spine dynamics

Inadequate blood supply (ischemia), resulting in neuronal cell death caused by stroke, cardiac arrest or profound hypotension is a leading cause of death and permanent disability. Brain damage resulting from ischemic injury typically manifests as the immediate loss of neurons within the ischemic core, surrounded by a region of brain tissue exposed to reduced blood flow and oxygen called the penumbra or peri-infarct region. This peri-infarct region has been the target of therapeutic protection following ischemic insult (e.g. stroke), and is thought to play a potentially critical role in functional recovery following stroke. Although the precise mechanisms of underlying delayed neuronal cell death are multi-faceted, the over-activation of N-methyl-D-spartate receptors (NMDARs), is known to have a key role in mediating neuronal injury in both in vitro and in vivo models of stroke and traumatic brain injury. Dr. Allen Chan is examining the role of selective NMDAR activation and blockade on dendritic spine dynamics immediately following a focal ischemic stroke, with the aid of established pharmacological treatments and in vivo brain imaging techniques. Dendritic spines are hypothesized to be key structural substrates within the penumbra that mediate plasticity changes necessary for functional recovery after stroke. Dr. Chan’s project will increase our understanding of the mechanisms and pathology of stroke injury with respect to the damage and death caused to pivotal brain cell connections called synapses, and ways to potentially alleviate this damage and death. In so doing, rescue and protection of damaged but repairable parts of the brain may lead to treatments that enhance functional recovery and therapies that directly impact patient health and quality of life.