Pathological changes and aquaporin-4 expression after bevacizumab treatment of traumatic penumbra in the rat brain.

The traumatic penumbra (TP) is a secondary injury zone surrounding the core area of traumatic brain injury (TBI) and plays a critical role in determining TBI outcomes. The primary pathological change in the TP is brain edema, which includes both vasogenic and intracellular edema. Brain edema is closely associated with the expression of aquaporin-4 (AQP4). Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, reduces vascular permeability. However, the effect of bevacizumab on traumatic brain edema remains unclear, as does its potential molecular mechanism in relation to AQP4. To examine the pathological changes and alterations in AQP4 expression following bevacizumab treatment in the TP. A total of 70 Wistar rats were randomly divided into five groups: a control group, a sham group, a TBI group, a TBI + normal saline group, and a TBI + bevacizumab group. Twenty-four hours after treatment, TP tissue samples were collected for analysis. Histopathological structural changes were examined using hematoxylin-eosin staining and transmission electron microscopy. Western blot was employed to assess changes in AQP4 protein levels, and double-labeling immunofluorescence was utilized to observe the AQP4 and VEGF. After TBI, the primary pathological changes in the TP were characterized by cerebral edema, which included both vasogenic and intracellular edema. Bevacizumab treatment reduced both types of edema. After TBI, AQP4 and VEGF expression in the TP was upregulated, and depolarization of AQP4 distribution was observed. However, bevacizumab treatment led to a downregulation of AQP4 and VEGF expression, and suppression of the AQP4 depolarized distribution. Bevacizumab alleviates cerebral edema in the TP after TBI by modulating the expression and polarized distribution of AQP4. Thus, bevacizumab may serve as a potential therapeutic agent for the clinical treatment of TP.