可注射脑源性细胞外基质水凝胶对大鼠脑内出血后功能恢复的影响OA

Objective To investigate the regulatory effect of an injectable brain-derived extracellular matrix(BdECM)hydrogel on rat motor functional recovery and angiogenesis after intracerebral hemorrhage(ICH).Methods Decellularized BdECM was prepared from the cerebral cortex of SD rats using a modified acid-enzyme combined method.The BdECM was digested with pepsin and pH-induced to form a hydrogel,whose physicochemical properties were characterized by scanning electron microscopy(SEM)and rheological analysis.Twenty male SD rats were randomly divided into sham,ICH,ICH+PBS,and ICH+Hydrogel groups.AnICHmodel was established by injecting autologous blood into the caudate nucleus.On day 7 post-surgery,equal volume PBS or BdECM hydrogel was injected into the hematoma cavity.Neurological functional recovery was assessed on days 7,14,and 21 post-surgery using corner test,rotarod test,and foot fault test.On day 21,immunofluorescence staining was performed to detect the expression of vascular endothelial growth factor A(VEGFA),von Willebrand factor(VWF),laminin β1,CD31,and CD34 in the peri-hematoma region.Hematoxylin and eosin(HE)staining was used to observe histopathological changes.Results The BdECM hydrogel was successfully prepared with a porous three-dimensional structure(confirmed by SEM)and self-healing properties,exhibiting a storage modulus of 442.61 Pa.Behavioral tests showed that compared to theICHand ICH+PBS groups,the ICH+Hydrogel group demonstrated significantly improved turning preference in the corner test(P<0.05),prolonged latency in the rotarod test(P<0.05),and reduced error rate in the foot fault test(P<0.05).Immunofluorescence results indicated that the fluorescence intensities of VEGFA,VWF,laminin β1,and the density of CD31/CD34-positive microvessels in the peri-hematoma region were significantly higher in the ICH+Hydrogel group than in theICHand ICH+PBS groups(P<0.05).HE staining showed significantly alleviated histopathological damage around the hematoma in the ICH+Hydrogel group.Conclusions The BdECM hydrogel effectively promotes rat motor functional recovery after ICH,potentially through enhancing angiogenesis in the peri-hematoma region.