Neuroprotective effects of protease-activated receptor-1 antagonist, SCH79797, on early stage of brain injury and expression patterns of brain-derived neuro trophic factor and nerve growth factor after subarachnoid hemorrhage in rats

Objective To investigate the neuroprotective effects of protease-activated receptor (PAR)-1 antagonist SCH79797 on early stage of brain injury and expression patterns of brain-derived neuro trophic factor (BDNF) and nerve growth factor (NGF) after subarachnoid hemorrhage (SAH) in rats. Methods Fifty-four clean male SD rats were randomly divided into three groups: sham-operative group, SAH group and treatment group (n=18). SAH rat models in the later two grou ps were induced by single cisterna magna blood injection. Rats in the treatment group were given SCH79797 (25 μg/kg) after SAH modeling. Neurologic function was assessed and scored after SAH for 24 h. Then the rats were sacrificed, and then, the brains were collected for determination of brain water content. The expression patterns of BDNF and NGF in cerebral tissues were tested by enzyme linked immunosorbent assay and immunofluorescence method. Results As compared with rats in the SAH group, rats in the treatment group had significantly increased neurological deficit scale scores (12.11 ± 2.62 vs. 14.59±2.24), statistically decreased water content in brain tissues (83.01% ± 0.38% vs. 79.79% ±0.44%), with significant difference (P<0.05). As compared with those in the SAH group, the expressions of BDNF and NGF in treatment group were significantly higher ([100.15±59.13] pg/mL vs. [368.00±137.52] pg/mL; [33.44±2.21] pg/mL vs. [37.49±2.29] pg/mL, P<0.05). As compared with those in the SAH group, the immunofluorescent staining intensities of BDNF and NGF in treatment group were significantly higher (41.65±1.50 vs. 91.40±1.30; 23.50±1.70 vs. 30.65±1.80, P<0.05). Conclusion SCH79797 given early may reduce the degree of brain edema and increase the expressions of BDNF and NGF, which has obvious neuroprotective effect. Key words: Subarachnoid hemorrhage; Early brain injury; Protease-activated receptor-1; Antagonist SCH79797; Brain-derived neuro trophic factor; Nerve growth factor