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

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.

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.

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.

In summary, we discovered that granisetron had neuroprotective properties in a rat model of radiation-induced brain damage.