Adaptive Immunity in Ischemic Stroke
Stroke is the fifth leading cause of death in the United States and a leading cause of disability. An ischemic stroke – the most common type of stroke – occurs as a result of an obstruction within a blood vessel supplying blood to the brain. Little progress has been made toward finding new treatments for ischemic stroke beyond administering the clot-busting drug called tPA. Our research will provide a better understanding regarding the activation of the immune system after stroke and the contribution of T cells to expanding ischemic brain injury. Such understanding could aid the design of new therapies to improve the clinical outcome for stroke patients.
Interleukin-15 in Ischemic Stroke
Stroke is a devastating event that causes significant morbidity and mortality. Clinical and preclinical experimental studies have highlighted the contributions from infiltrating lymphocytes to the progression of cerebral infarction after ischemic stroke, but the impact of local factors on central nervous system (CNS)- infiltrating lymphocytes in the specific context of stroke have not been studied in depth.
Interleukin (IL)-15 is a proinflammatory cytokine that is pivotal for lymphocytic activities. Astrocytes are implicated as contributors to immune responses taking place in the CNS and a major source of IL-15. Results from this project will provide valuable new knowledge concerning the role of IL-15 in regulating immune responses in ischemic brain injury. Furthermore, results from these studies could lead to the development of new therapeutic strategies designed to attenuate the progression of brain damage following stroke.
Modulation of Vascular Inflammation in Acute Ischemic Stroke
Acute ischemic stroke (AIS) is a serious health problem worldwide. Current therapies for this devastating disease are far from optimal. Tissue plasminogen activator (tPA) administered within 4.5 hours of symptom onset restores cerebral blood flow and promotes neurological recovery in stroke patients. However, this narrow time frame and the risk of intracerebral hemorrhage after tPA treatment pose major drawbacks to its clinical usage.
The development of neurovascular protectants to treat AIS has been beset by disappointments and setbacks. Armed with the insight that the immune system participates in ischemic brain injury and our increasing ability to modulate the immune system, we are exploring immune interventions as a new therapeutic avenue for improving outcomes in acute stroke patients.
Three proof-of-concept studies using fingolimod have demonstrated that immunomodulation in stroke patients is feasible. The goal of this project is to use immune modulation as a viable approach to overcome the limitations of tPA treatment. The results from this project demonstrate strong potential for the application of immune modulators as a safe and effective therapy for patients with ischemic stroke.