Increasing evidence has revealed that exercise produces endogenous protection in focal cerebral ischemia through a variety of mechanisms. However, whether exercise preconditioning promotes protection in stroke by enhancing the integrity of the neurovascular unit (a construct consisting of microvascular endothelium, astroglia, neurons, and the extracellular matrix) has never been investigated.
We first determine if exercise enhances brain microvascular integrity against ischemia/reperfusion injury by maintaining blood brain barrier (BBB) function and proper structural relations of endothelium, astrocyte, and intervening basal lamina in the neurovascular unit, leading to functional recovery after stroke. We investigate if the reduction in ischemic injury is caused by endothelial and astrocytic integrin upregulation after exercise preconditioning. Finally, we elucidate causal roles of tumor necrosis factor-alpha (TNF-alpha) induced during exercise in mediating integrin expression as well as BBB function and behavioral outcome. Identification of the TNF-alpha-integrin mechanism in exercise-induced neuroprotection would help establish an efficacious approach for stroke treatment beyond levels achieved by current studies. Insights gained by this investigation are also likely to refine evolving concepts of the neurovascular unit.
Recent Publications in Peer-reviewed Journals:
Ding YH, Rafols, JA, Li J, Denise A. Bessert, Ding Y. (2005) Exercise Pre-conditioning Strengthens Brain Microvascular Integrity in A Rat Stroke Model. Neurological Res.
Ding YH, Rafols, JA, Li J, Denise A. Bessert, Ding Y. (2005) Upregulation of Tumor Necrosis Factor- a and Integrins After Exercise Pre-conditioning Enhances Cerebrovascular Integrity in Ischemic Rats.
Ding Y, Clark JC (2006) Cerebrovascular Injury in Stroke. Neurological Res. 28 (1):3-10.
Ding YH, Rafols HA, Li J, McAllister JP II, Guthinkonda M, Ding Y. (2006) Neuroprotective Effect of Exercise Pre-conditioning on Brain Integrity After Experimental Stroke in Rats. Neurological Res. 28 (2):184-9.
Ding YH, Li J, Rafols JA, Clark JC, Ding Y. (2006) Upregulation of Tumor Necrosis Factor-α and Integrins After Exercise Pre-conditioning Enhances Cerebrovascular Integrity in Ischemic Rats. Acta Neuropathologica. 112 (1):74- 84.
Davis W, Mahale S, Ding Y. (2007) Exercise Ameliorates BBB Dysfunction in Stroke by Enhancing Basal Lamina. Neurological Res. (in press).