Immunologic Implications for Stroke Recovery: Unveiling the Role of the Immune System in Pathogenesis, Neurorepair, and Rehabilitation.

Abstract

Stroke is a debilitating neurologic condition characterized by an interruption or complete blockage of blood flow to certain areas of the brain. While the primary injury occurs at the time of the initial ischemic event or hemorrhage, secondary injury mechanisms contribute to neuroinflammation, disruption of the blood-brain barrier (BBB), excitotoxicity, and cerebral edema in the days and hours after stroke. Of these secondary mechanisms of injury, significant dysregulation of various immune populations within the body plays a crucial role in exacerbating brain damage after stroke. Pathological activity of glial cells, infiltrating leukocytes, and the adaptive immune system promote neuroinflammation, BBB damage, and neuronal death. Chronic immune activation can additionally encourage the development of neurologic deficits, immunosuppression, and dysregulation of the gut microbiome. As such, immunotherapy has emerged as a promising strategy for the clinical management of stroke in a highly patient-specific manner. These strategies include regulatory T cells (Tregs), cell adhesion molecules, cytokines, and monoclonal antibodies. However, the use of immunotherapy for stroke remains largely in the early stages, highlighting the need for continued research efforts before widespread clinical use.