Abstract
Docosahexaenoic acid complexed to albumin (DHA-Alb) is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo), but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270–330 g) underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg), Alb (0.63 or 1.25 g/kg), DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg) or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7–10 per group). Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg) by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36–40%) and moderate doses (by 34–42%) of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.
Highlights
Ischemic stroke is one of the leading causes of morbidity and mortality worldwide
Alb and Docosahexaenoic acid complexed to albumin (DHA-Alb) therapy led to the expected moderate reduction in hematocrit compared to the vehicle groups (Table 1)
Our results clearly indicate that Docosahexaenoic acid (DHA)-Alb therapy substantially improves neurological function and reduces T2 weighted images (T2WI) lesion and infarct volumes in rats after permanent middle cerebral artery occlusion (MCAo)
Summary
TPA, is currently the only therapeutic option available for stroke treatment. Its thrombolytic properties provide a means to break up blood clots during the hyper-acute phase of stroke, allowing for reperfusion of the ischemic area. The use of tPA is restricted by a narrow therapeutic window (it is only approved to be administered up to 4.5 h after stroke onset) and has multiple absolute contraindications, especially for individuals with any increased bleeding risk. In pre-clinical studies, the neuroprotective potential of new therapies is assessed by several variations of experimentally-induced ischemia but these tend to be transient focal cerebral ischemia models. Because the majority of strokes do not resolve with immediate reperfusion, it is vital that potential therapeutic compounds are studied using a permanent occlusion animal model as well
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