Investigation of the neuroprotective effect of Granisetron through SV2A and 5-HT3 modulation in a radiation-induced brain injury rat model

Background: the development of neurotoxicity in healthy, non-targeted brain tissue exposed to radiation during cranial radiotherapy (rt) is the most frequent event of radiation-induced adverse effects. the 5-hydroxytryptamine-3 (5-ht3) receptor antagonists may also have a range of neuroprotective, anti-inflammatory, and antiphlogistic properties in addition to their anti-emetic effects. materials and methods: study groups were formed in the following ways: group 2: irradiation (ir)-only (ir+saline); group 1: normal control (orally fed control); group 3: ir+granisetron (ir+granisetron): whole-brain ir and granisetron 1 mg/kg/day (merck) administered orally. 15 days of all therapies were given. the 15 days were completed with behavioral testing. in the entire brain ir-only (placebo) group, a substantial deterioration was seen in all studied marker levels and behavioral test results. results: compared to the ir-only group, all of these biochemical indicators significantly improved in the granisetron group (ir+granisetron), and levels of the control group returned to normal. in behavioral test analyses, a substantial decline in the open field and passive avoidance learning social recognition tests was seen in the ir-only group compared to the healthy control group, whereas an improvement was seen in the ir+granisetron group. in addition, the ir-only group showed a reduction in hippocampus neurons and purkinje neurons as well as an increase in hippocampal gliosis, whereas the ir+granisetron group showed an improvement and a return to the normal control group counts. conclusion: in summary, we discovered that granisetron had neuroprotective properties in a rat model of radiation-induced brain damage.