The role of crocetin in protection following cerebral contusion and in the enhancement of angiogenesis in rats

The protective role of crocetin following cerebral contusion and its effects on the enhancement of angiogenesis in rats was investigated. A total of 60 Sprague-Dawley rats were divided into three groups (n = 20 each): crocetin therapy group (cerebral contusion treated with crocetin), cerebral trauma control group (without treatment), sham operation control group. The effect of crocetin was examined by modified Neurological Severity Scores (mNSS), electron microscopy, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) procedure, western blotting analysis of Bcl-2 protein expression, microvessel count (MVC), endothelial cell culture and immunocyto-chemistry. The mNSS results indicated that neurological function of therapy group was significantly recovered seven days and fifteen days after the trauma. The TUNEL staining and electron microscopy revealed that crocetin treatment led to an inhibition of neuronal apoptosis 72 h following treatment; this finding was confirmed by western blot analysis of B cell lymphoma/leukemia-2 (Bcl-2) protein expression. Expression levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and serum response factor (SRF) were higher in the crocetin therapy group in comparison to the two other experimental groups. Our results demonstrate that the protective effects of crocetin upon brain injury may be related to its ability to inhibit apoptosis at early stages of the injury and its ability to promote angiogenesis at the sub-acute stage. (C) 2011 Published by Elsevier B.V.