Mild traumatic brain injury increases vulnerability to cerebral ischemia in mice

Exp Neurol. 2021 May 13:113765. doi: 10.1016/j.expneurol.2021.113765. Online ahead of print.ABSTRACTRecent studies have reported that TBI is an independent risk factor for subsequent stroke. Here, we tested the hypothesis that TBI would exacerbate experimental stroke outcomes via alternations in neuroimmune and neurometabolic function. We performed a mild closed-head TBI and then one week later induced an experimental stroke in adult male mice. Mice that had previously experienced TBI exhibited larger infarcts, greater functional deficits, and more pronounced neuroinflammatory responses to stroke. We hypothesized that impairments in central metabolic physiology mediated poorer outcomes after TBI. To test this, we treated mice with the insulin sensitizing drug pioglitazone (Pio) after TBI. Pio prevented the exacerbation of ischemic outcomes induced by TBI and also blocked the induction of insulin insensitivity by TBI. However, tissue respiratory function was not improved by Pio. Finally, TBI altered microvascular responses including promoting vascular accumulation of serum proteins and significantly impairing blood flow during the reperfusion period after stroke, both of which were reversed by treatment with Pio. Thus, TBI appears to exacerbate ischemic outcomes by impairing metabolic and microvascular physiology. These data have important implications because TBI patients experience strokes at greater rates than individuals without a history of head injury, but these data sug...

Source: Experimental Neurology - May 16, 2021 Category: Neurology Authors: Zachary M Weil Kate Karelina Bailey Whitehead Ruth Velazquez-Cruz Robin Oliverio Mark Pinti Divine C Nwafor Samuel Nicholson Julie A Fitzgerald John Hollander Candice M Brown Ning Zhang A Courtney DeVries Source Type: research