Surviving Cerebral Ischemia
Dr. Rona Giffard's laboratory studies stroke. Stroke is a devastating problem that is the leading cause of long term neurological disability and the third leading cause of death worldwide. We try to identify ways to reduce ischemic brain injury, and to better understand the interactions between different brain cell types during injury and recovery. Astrocytes and their response to injury is an important focus in the lab. We have found that astrocyte impairment contributes to neuronal injury in global ischemia. Targeting protective strategies to astrocytes leads to markedly increased neuronal survival.
Another area of focus in the lab is the increase in neurogenesis following stroke, and the deleterious effects of inflammation on neurogenesis in this setting. We are studying ways to improve mitochondrial function to increase newborn neuron survival, and modulate inflammation.
MicroRNAs are small noncoding RNAs that reduce translation and thus inhibit gene expression. Recent work shows that microRNAs are regulated in response to stroke, and may play an important role in neuroprotection. We are studying microRNAs that regulate important survival proteins including members of the Bcl-2 family and heat shock proteins. Because each microRNA can target multiple messengerRNAs, this is a way to target several physiologically related genes at once.
Inflammation following stroke while having important necessary roles, can also contribute to worsening injury. We have investigated the importance of IL4 in stroke, and found that it protects male mice from stroke injury. Results in females however, differed. Biological sex differences are seen in differences in the age of stroke and outcome to stroke in patients. We are also investigating sex differences in response to stroke, with a focus on differences in inflammation.
Studies are performed in animal models and primary cultures from brain.
- Gene therapy for stroke with heat shock proteins especially members of the Hsp70 family, antiapoptotic proteins (bcl-2 and bcl-x), and antioxidant proteins
- Role of astrocyte impairment in global ischemia
- Role of mitochondria in neurogenesis, stress, inflammation, and cell death signaling
- Cell type specific injury studying isolated neurons, astrocytes, microglia, and endothelial cells
- Cell-cell interactions of theses cell types during injury using different types of mixed cultures, brain slices, and transgenic animals.
- Role of inflammation in brain injury
- Effects of development and sex differences on vulnerability to injury and type of cell death
- microRNAs as novel targets in cerebral ischemia