Role of calcium sensing receptor in the rat＇s neuronal apoptosis after traumatic brain injury

Abstract

Objective To investigate the apoptosis expression and role of calcium sensing receptor (CaSR) induced by traumatic brain injury (TBI) in rats. Methods Fifty-four healthy male SD rats were randomly divided into 3 groups: the control group, TBI group and inhibitor group (n=18). Each group was divided into 3 subgroups: 6 hours, 24 hours, and 72 hours (n=6). TBI animal models in the TBI and inhibitor groups were established using Feeney＇s method. CaSR antagonist NPS2390 (10 μmol/kg) was infused through caudal vein for 2 days before the establishment in the inhibitor group. Modified Neurological Severity Scores (mNSS) was used to evaluate the neurological behavior of rats in each group. Real-Time PCR was used to detect expressions of CaSR and Caspase-3 mRNA. Western blot was used to detect the protein expression of CaSR and Caspase-3 protein. TUNEL assay was used to detect neuronal apoptosis. Results (1) The results showed that the mNSS scores in TBI group compared with the control group and inhibitor group were increased in 6 h, 24 h, 72 h after modeling (P<0.01). (2) In both TBI and inhibitor groups, the mRNA and protein expressions of CaSR and Caspase-3 reached the peak at 24h (P<0.01). Compared with the control group and the inhibitor group, the expression of CaSR mRNA and its protein were increased in the TBI group (P<0.01). The expression of Caspase-3 was higher in the TBI group than that in the control and inhibitor groups at 24 h only (P<0.05). (3) The results of TUNEL assay showed that apoptosis reached the peak level at 24 h after TBI model was made (P<0.05). The TBI group had more apoptotic cells compared with the other 2 groups (P<0.01). (4) There was a positive correlation between CaSR as well as Caspase-3 and neuronal apoptosis (r=0.300, P<0.05; r=0.371, P<0.01). The protein expressions of CaSR and Caspase-3 had a positive correlation (r=0.434, P<0.01). Conclusion CaSR may play an important role in neuronal apoptosis in the rat model of TBI. Key words: Craniocerebral trauma; Receptors, calcium-sensing; Apoptosis; Rats