Exogenous insulin-like growth factor 1 attenuates acute ischemic stroke-induced spatial memory impairment via modulating inflammatory response and tau phosphorylation.

Acute ischemic stroke is one of the main causes of mortality and morbidity worldwide. The present study aimed to explore the effects of exogenous insulin-like growth factor 1 (IGF-1) on the cognitive injuries induced by acute ischemic stroke and the underlying mechanisms. Acute ischemic stroke rat model was established via transient occlusion of the left middle cerebral artery to male Sprague-Dawley rats. IGF-1 was administered intravenously every other day 24 h after surgery for 14 days. Cognitive functions were determined by Morris water maze assay. Cerebral infarction and edema were determined by riphenyltetrazolium chloride staining and cerebral water content measurement. ELISA and Western blot were performed to detect concentrations of target proteins. Ischemic stroke rats exhibited reduced plasma IGF-1 level and impaired cognitive functions. Intravenous IGF-1 delivery increased the IGF-1 levels in plasma, ischemic amygdala, hippocampus and cortex, improved the neurological dysfunction, cognitive deficits, cerebral infarction and brain edema. Furthermore, IGF-1 relieved the systemic and cerebral inflammatory response by inhibiting the secretion of pro-inflammatory cytokines, interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α), in serum and ischemic hippocampus of ischemic rats. Additionally, IGF-1 attenuated tau phosphorylation in ischemic hippocampus. In short, intravenous IGF-1 administration attenuates acute ischemic stroke-induced cognitive injuries in the experimental rat model possibly via modulating inflammatory response and tau phosphorylation, and might be of promising therapeutic value to ischemic stroke in the future.