High levels of NGF during anxiety-like behavior in a murine model of brain ischemic stroke

Abstract Purpose Neuropsychiatric disorders following stroke, including depression and anxiety, are often associated with long-term disability. Neurotrophic factors play an important role in the pathophysiology of many neurodegenerative and neuropsychiatric disorders. In the current study, we investigated a potential participation of neurotrophic factors in stroke-associated behavioral and pathological changes 14 days after ischemia. Methods Transient global cerebral ischemia was induced by bilateral occlusion of common carotid arteries (BCCAo) in C57BL/6 mice. Neurological evaluation was performed daily up to 14 days after induction. The Open Field (OF) and Elevated Plus Maze (EPM) tests were performed. After behavioral tests, brains from sham and ischemic mice were removed and processed to evaluate histopathology and immunomarcation for cleaved caspase-3 as well as the neurotrophic factors brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), and neural growth factor (NGF) by ELISA. Results Ischemic animals presented anxiety-like behavior and histopathological alterations mainly characterized by formation of small necrotic cavities surrounded by penumbra zone and neuropil vacuolation in the frontal cortex, ischemic neurons in the hippocampus and gliosis in the midbrain. Some immunopositive neurons for cleaved caspase-3 were observed in the penumbra by immunohistochemical analysis. Higher levels of NGF were found in the brain of BCCAo mice compared with sham animals. Similar concentrations of BDNF and GDNF were detected in both groups. Conclusion Our results suggested the participation of NGF in anxiety-like behavior at 14 days after induction of experimental cerebral ischemia and reperfusion.