Importance of Angiogenin and Endothelial Progenitor Cells After Rehabilitation Both in Ischemic Stroke Patients and in a Mouse Model of Cerebral Ischemia

Background: Rehabilitation therapy is the only available treatment for stroke survivors presenting neurological deficits; however, the underlying molecules and mechanisms associated with functional/motor improvement during rehabilitation are poorly understood. Objective: Our aim is to study the modulation of angiogenin and endothelial progenitor cells (EPCs) as repair-associated factors in a cohort of stroke patients and mouse models of rehabilitation after cerebral ischemia. Methods: The clinical study included 18 ischemic strokes admitted to an intensive rehabilitation therapy (IRT) unit, 18 non-ischemic controls and brain samples from three deceased patients. Angiogenin and EPCs were measured in blood obtained before and up to 6 months after IRT together with an extensive evaluation of the motor/functional status. In parallel, C57BL/6 mice underwent middle cerebral artery occlusion, and the pasta matrix reaching-task or treadmill exercises were used as rehabilitation models. Angiogenin RNA expression was measured after 2 or 12 days of treatment together with cell counts from EPCs cultures. Results: Brain angiogenin was identified in both human and mouse tissue, whereas serum levels increased after 1 month of IRT in association with motor/functional improvement. EPC populations were increased after stroke and remained elevated during follow-up after IRT. The mouse model of rehabilitation by the task-specific pasta matrix exercise increased the number of EPCs at 2 days and increased angiogenin expression after 12 days of rehabilitation. Conclusions: Angiogenin and EPCs are modulated by rehabilitation after cerebral ischemia, suggesting that both angiogenin and EPCs could serve as biomarkers of improvement during rehabilitation or future therapeutic targets.