Investigation of the efficacy of bevacizumab treatment in an experimental rat model of chronic subdural hematoma

Introduction: Especially with the advances in medicine, the elderly population has increased in the world and chronic subdural hematoma (CSDH) is a common neurosurgical pathology that will increase in incidence in the future. Considering that surgical comorbidity and mortality increase with age, medical treatments are being investigated for patients who do not meet the neurologic criteria for surgery. In our study, we compared the efficacy of bevacizumab treatment with combined dexamethasone (DEX) and atorvastatin (ATO), the current conventional medical treatment, in a model of CSDH. Materials and method: 95 rats were divided into 4 groups of sham operation (n=18), control hematoma (n=18), DEX-ATO (n=18) and bevacizumab (n=18). In these groups, except for the sham group, 400μl + 300μl autologous blood was injected into the subdural space with an interval of 72 hours. In the sham operation, all steps except the injection step were performed. Intraperitoneal (i.p.) SF was administered to the control hematoma group, DEX-ATO group was administered by gavage and bevacizumab group was administered i.p. for 10 days. Six rats from all groups were sacrificed on days 7, 14 and 21 and freshly removed brain samples were analysed for VEGF-A, VEGF-C, VEGF-D, IL-6 and IL-8 levels by ELISA and immunohistochemical analysis. At the same time, weight differences, hematoma and surrounding ischemic tissue volume were measured. 23 rats were excluded for various reasons. Results: While hematoma volumes decreased with time in all modeled groups, hematoma volumes in the control hematoma group were higher than those in the medically treated groups. While weights decreased with time, DEX-ATO treatment resulted in more weight loss. Both bevacizumab and DEX-ATO showed similar anti-inflammatory effect and hematoma volume reduction. Discussion: The results showed that bevacizumab treatment and conventional therapy had a similar effect on reducing hematoma volume. However, bevacizumab exhibited superior neuroprotective effects compared to conventional therapy. Furthermore, bevacizumab was better tolerated than conventional therapy, indicating its potential as a viable treatment option for patients with CSDH. These findings also suggest that macrophages may play a crucial role in the pathogenesis of CSDH, highlighting the need for further studies in this area. Key Words: Chronic subdural hematoma, bevacizumab, dexamethasone, atorvastatin, rat model