Abstract
Preclinical studies using rodent models of stroke have had difficulty in translating their results to human patients. One possible factor behind this inability is the lack of studies utilizing aged rodents of both sexes. Previously, this lab showed that leukemia inhibitory factor (LIF) promoted recovery after stroke through antioxidant enzyme upregulation. This study examined whether LIF promotes neuroprotection in aged rats of both sexes. LIF did not reduce tissue damage in aged animals, but LIF-treated female rats showed partial motor skill recovery. The LIF receptor (LIFR) showed membrane localization in young male and aged rats of both sexes after stroke. Although LIF increased neuronal LIFR expression in vitro, it did not increase LIFR in the aged brain. Levels of LIFR protein in brain tissue were significantly downregulated between young males and aged males/females at 72 h after stroke. These results demonstrated that low LIFR expression reduces the neuroprotective efficacy of LIF in aged rodents of both sexes. Furthermore, the ability of LIF to promote motor improvement is dependent upon sex in aged rodents.
Highlights
Stroke is the fifth leading cause of death among Americans and a leading cause of major disability
Our study shows that leukemia inhibitory factor (LIF) treatment is less effective at promoting neuroprotection after middle cerebral arterial occlusion (MCAO) in aged rats of both sexes, which coincides with significantly lower LIF receptor (LIFR) expression in the brain compared to young rats
Magnetic resonance Imaging (MRI) scans were used to measure the volume of edema (T2) and infarcted tissue (DTI) in the brains of PBS and LIF-treated aged rats
Summary
Stroke is the fifth leading cause of death among Americans and a leading cause of major disability. One of the most damaging types of ischemic stroke, an emergent large vessel occlusion (ELVO), occurs when a thrombus impedes blood flow in a major cerebral artery. Intravenous administration of tissue plasminogen activator (tPA), the only FDA-approved drug for ischemic stroke, is often ineffective in ELVO patients (Broderick et al, 2013; Ciccone et al, 2013; Kidwell et al, 2013), and others are unable to undergo endovascular thrombectomy (EVT). The permanent intraluminal middle cerebral arterial occlusion (MCAO) model of stroke best represents ELVO without tPA administration or EVT.
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