VEGFA induces anxiety and depression-like behaviors in post-stroke mice by regulating the permeability of the blood-brain barrier

Abstract

Post-stroke depression (PSD) is the most common neuropsychiatric sequela of stroke, and its pathogenesis remains unclear. The blood-brain barrier (BBB) is an important barrier for maintaining the normal operation of neurons. The impairment of its function leads to the occurrence of various neurological diseases. Vascular endothelial growth factor A (VEGFA) is an important factor in regulating the permeability of the BBB. Its expression increases after stroke and aggravates brain injury. However, the role of VEGFA in PSD remains unclear. We used middle cerebral artery occlusion combined with shock to establish a PSD mouse model and evaluated the anxiety and depression-like behaviors of the mice through behavioral tests. The permeability of the BBB, the inflammatory response, and the expression levels of VEGFA and tight junction proteins in the hippocampus of PSD mice were detected. The results showed that middle cerebral artery occlusion combined with shock could lead to severe anxiety and depression-like behaviors in mice, and the increased expression of VEGFA led to BBB damage in PSD mice. Bevacizumab improved the permeability of the BBB, alleviated the inflammatory response in the hippocampus, and promoted neuronal repair in PSD mice by inhibiting VEGFA/VEGFR, thereby improving the depression-like behaviors of PSD mice. In conclusion, the above results indicate that VEGFA participates in the depression-like behaviors of PSD mice by regulating the permeability of the BBB.

Keywords: Blood-brain barrier; Post-stroke depression; Tight junction; Vascular endothelial growth factor A.