Abstract
Cognitive impairment and memory loss are commonly seen after stroke and a third of patients will develop signs of dementia a year after stroke. Despite a large number of studies on the beneficial effects of neuroprotectants, few studies have examined the effects of these compounds/interventions on long-term cognitive impairment. Our previous work showed that the microRNA mir363-3p reduced infarct volume and sensory-motor impairment in the acute stage of stroke in middle-aged females but not males. Thus, the present study determined the impact of mir363-3p treatment on stroke-induced cognitive impairment in middle-aged females. Sprague–Dawley female rats (12 months of age) were subjected to middle cerebral artery occlusion (MCAo; or sham surgery) and injected (iv) with mir363-3p mimic (MCAo + mir363-3p) or scrambled oligos (MCAo + scrambled) 4 h later. Sensory-motor performance was assessed in the acute phase (2–5 days after stroke), while all other behaviors were tested 6 months after MCAo (18 months of age). Cognitive function was assessed by the novel object recognition test (declarative memory) and the Barnes maze (spatial memory). The MCAo + scrambled group showed reduced preference for a novel object after the stroke and poor learning in the spatial memory task. In contrast, mir363-3p treated animals were similar to either their baseline performance or to the sham group. Histological analysis showed significant deterioration of specific white matter tracts due to stroke, which was attenuated in mir363-3p treated animals. The present data builds on our previous finding to show that a neuroprotectant can abrogate the long-term effects of stroke.
Highlights
Cognitive impairment is a common consequence after a stroke that significantly impairs the patient’s functional recovery as well as the quality of life
Sensorimotor deficits were assessed by the adhesive tape removal test, where latency to tape removal from the paw contralateral is increased after middle cerebral artery occlusion (MCAo), and this measure is well correlated with the extent of infarction
This study focused on long-term cognitive impairment after stroke in acyclic middle-age rats and the effect of microRNA treatment
Summary
Cognitive impairment is a common consequence after a stroke that significantly impairs the patient’s functional recovery as well as the quality of life. Mir363-3p Attenuates Stroke-Induced Cognitive Impairment prevalence of cognitive decline after stroke increases exponentially with age (Gorelick et al, 2011). Previous or recurrent stroke, the volume of infarction, location of the stroke, and female sex are all strongly associated with post-stroke cognitive impairment (Pendlebury and Rothwell, 2009). Among these survivors, women are more likely to require assisted living facilities because of deteriorating cognitive function (Gall et al, 2012; Bushnell and McCullough, 2014; Bushnell et al, 2014)
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