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Resveratrol Delivery by Albumin Nanoparticles Improved Neurological Function and Neuronal Damage in Transient Middle Cerebral Artery Occlusion Rats.

ABSTRACT: Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances. It is demonstrated in this study that the regional accumulation of albumin in the ischemia-reperfusion (I/R) brain may lead in the application of HSA based nanoparticles in the study of cerebral I/R injury. Resveratrol (RES) is potential in the treatment of cerebral I/R injury but is restricted for its water insolubility and short half-life in vivo. In our study, RES loaded HSA nanoparticles (RES-HSA-NPs) were prepared to facilitate the application of RES in protection from cerebral I/R injury. RES-HSA-NPs demonstrated spherical shape, a diameter about 100 nm, a highest RES encapsulation efficiency of 60.9 ± 5.07%, and controlled release pattern with the maximum release ratio of 50.2 ± 4.91% [in pH = 5.0 phosphate buffered saline (PBS)] and 26. 2 ± 2.73% (in pH = 7.4 PBS), respectively, after 90 h incubation at 37°C. After intravenous injection into transient middle cerebral artery occlusion (tMCAO) rats, RES-HSA-NPs improved neurological score and decreased infarct volume at 24 h after tMCAO in a dose dependent manner. A single dose of 20 mg/kg RES-HSA-NPs via tail vein improved neurological outcomes and decreased infarct volume at 24 and 72 h in tMCAO rats. I/R increased oxidative stress (indicated by products of lipid peroxidation, MDA) and neuronal apoptosis (indicated by yellow-brown TUNEL-positive cells), RES-HSA-NPs significantly attenuated oxidative stress and neuronal apoptosis. These results demonstrated the potential of RES-HSA-NPs in the therapy of cerebral I/R injury.

SUBMITTER: Xu H

PROVIDER: S-EPMC6288361 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Project description:BackgroundType 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO).MethodsTransient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography-based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining.ResultsCompared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 (P<0.001) but not male control mice. When normalized to pre-MCAO baseline, red blood cell flux 24 hours after stroke was 64% lower in male DM2 mice than male nondiabetic controls (P<0.01). In females, MCAO decreased capillary flux by 48% at 24 hours post-MCAO compared with baseline in DM2 (P<0.05) but not in control mice. Red blood cell flux of female DM2 mice did not differ from that of nondiabetic controls either before or 24 hours after MCAO. Furthermore, normalized capillary flux 24 hours after MCAO failed to differ between female DM2 mice and nondiabetic controls. Concomitantly, male but not female DM2 mice experienced 25% larger infarct in caudate-putamen versus respective nondiabetic controls (P<0.05).ConclusionsDM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.

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Resveratrol Delivery by Albumin Nanoparticles Improved Neurological Function and Neuronal Damage in Transient Middle Cerebral Artery Occlusion Rats.

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