Stress and social isolation increase vulnerability to stroke

Abstract

Stress is a universal experience for living organisms. Under many circumstances activation of the hypothalamic-pituitary adrenal (HPA) axis is an adaptive response to stress. However, when stress or HPA activation is prolonged or its timing immediately precedes or coincides with an ongoing neurodegenerative process, the results can be deleterious. A causal relationship among stress, HPA axis activity, and stroke outcome exists. Stress is one of many potential triggers of ischemic stroke and sustained elevations in glucocorticoids compromise neuronal survival following an ischemic attack. Indeed, glucocorticoid exposure is a critical determinant of stroke outcome; prior exposure to stress and elevated peri-ischemic glucocorticoid concentrations are associated with poor outcome among stroke patients and in rodent models of cerebral ischemia. Likely, stress and glucocorticoid exposure exacerbate stroke by sensitizing the neuroimmune response to ischemia; stroke induces an upregulation of pro-inflammatory cytokines which contributes to migration of leukocytes into cerebral tissue and neuronal death. Social isolation also appears to compromise stroke outcome through priming of the neuroimmune system. Among individuals who survive the stroke, residual inflammation is apt to further compromise quality of life via its effect on cognitive function and affect. A better understanding of the mechanisms through which stress and social environment modulate neuroimmune function could lead to improved treatment of stroke and other neurodegenerative diseases.