T he oxygen energy failure due to the loss of blood supply results in major disturbances in ionic balance leading to depolarization and release of excitatory amino acids such as glutamate. Glutamate signals through receptors leading to further depolarization and the release of calcium. Being a potent second messenger calcium activated multiple enzymatic pathways lead to increased production of ROS and RNS and activation of different proteases. All these processes further increase cytotoxicity, which is especially critical for survival of already vulnerable neurons. The release of inflammatory mediators and many signals from damaged tissue result in recruitment of leukocytes from the periphery and activation of CNS residing immune cells.
Immune response plays integral part in the development of stroke. Global anti-inflammatory strategies to treat stroke, albeit promising, didn’t transform into standard treatments of stroke as immune system is already inhibited as a result of increased sympathetic activity. This immune depressed state increases risk of infection that increase expression of pro-inflammatory cytokines which leads to secondary complications in stroke patients. Therefore, novel approaches are needed to target inflammation within the developing core of the stroke lesion. This treatment has to augment wound-healing (resolution of inflammation) components of the immune response while inhibiting pro-inflammatory tissue damaging action of the immune response.
As part of our stroke recovery research, we are studying ways that augment existing feedback mechanisms to limit inflammatory response within the core and penumbra of the stroke lesion.