Multiplex Immunofluorescence-Based Investigation of the Interventional Effect of Bisdemethoxycurcumin on Glial Cell Polarization in Radiation-Induced Brain Injury

Radiation-induced brain injury (RIBI) is a severe and common complication following radiotherapy for intracranial tumors, primarily manifested as brain tissue damage, neuroinflammation, and cognitive dysfunction. Currently, clinically effective therapeutic options remain lacking, severely compromising patient prognosis and quality of life. Bisdemethoxycurcumin (BDMC) is a highly stable active derivative of curcumin with antioxidant, anti-inflammatory, and neuroprotective properties. However, the therapeutic effect and underlying mechanisms of BDMC against RIBI remain poorly defined. Objective: To investigate the neuroprotective effects of BDMC on RIBI in rats and to elucidate the molecular mechanisms that regulate glial cell polarization. Methods: Forty SPF-grade male Sprague–Dawley (SD) rats were randomly assigned to four groups (n = 12 per group): control, model, amifostine (AMF) and BDMC. A rat RIBI model was established by whole-brain irradiation with a single dose of 30 Gy X-rays, followed by the respective drug interventions. After 4 consecutive weeks of treatment, body weight was recorded, and brain water content and oxidative-stress indicators in brain tissue were quantified. Hematoxylin–eosin (HE) staining was performed to assess pathological injury in brain tissues. Multiplex immunohistochemistry (mIHC) was employed to quantitatively analyze the polarization states of microglia and astrocytes in the cerebral cortex, hippocampus, and thalamus. Results: Radiation-induced RIBI induced body-weight loss, cerebral edema, and cerebral oxidative-stress disturbance in rats, accompanied by neuronal edema, degeneration,