Effect of Tocilizumab in Subarachnoid Hemorrhage-induced Cerebral Vasospasm of Experimental Rats

Background: and Aim: This study aimed to evaluate the effects of Tocilizumab (TCZ), a recombinant humanized, anti-human monoclonal antibody of the immunoglobulin G1k subclass, on vascular morphological changes, endothelial apoptosis, and the levels of pro-inflammatory and apoptotic cytokines, such as IL-6, tumor necrosis factor-alpha (TNF-α), caspase-3, Bcl-2 associated X-protein (BAX), and vascular endothelial growth factor (VEGF) in a rat SAH model. Methods: : The rats were randomly assigned to 4 groups: (1) normal control (without SAH); (2) SAH (without treatment); (3) SAH treated with saline (SAH + Sal.); and (4) SAH treated with TCZ (SAH + Toc.). The tissues were measured using the enzyme-linked immunosorbent assay (ELISA) kits. A series of brain and basilar artery sections were categorized into several subgroups for hematoxylin and eosin (H&E) staining, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results: : The levels of caspase, BAX, and IL-6 in the SAH + TOC group were significantly lower than in the control, SAH, and SAH + SAL groups (p=0.029, p=0.016, and p=0.002 respectively). TCZ treatment significantly increased the lumen of the basilar artery compared with that in the SAH and SAH + SAL groups without treatment (p=0.002 and p=0.004 respectively). SAH increased the apoptotic index in the endothelium compared with TCZ treatment (p=0.027) groups. Conclusion: It can be concluded that TCZ is safe and effective for treating experimental SAH. The results reveal clearly experimental evidence for the potential clinical application of TCZ in SAH patients.