A2 improved survival and neurological function of TBI mice. C57BL/6J male mice were subjected to TBI and received 4 mg/kg of A2 through IP 30 minutes after injury. (A,B) Survival (n = 95) (A) and mNSS (n = 59) (B) were compared between mice receiving A2 and those receiving TBST (1-way ANOVA on rank, *P < .001 and **P < .005 vs untreated). (C-E) Hematoxylin and eosin brain histology on brain tissue collected 24 hours after TBI shows subdural hematoma (C,D, arrow) and multiple intracerebral hemorrhage (D,E, arrowhead) loci of mice receiving TBST. (F-H) The subdural (F, arrow) and intracerebral bleeding (G, arrow) were observed less frequently in TBI mice receiving A2 (H, the brain of a sham mouse as control). The images are representative of 36 mice examined. (I) Hemoglobin in brain homogenates at 24 and 72 hours after TBI (n = 9, 1-way ANOVA). (J-L) Coronal views of the brains from TBI mice receiving TBST (J) or A2 (K) and sham mice (L) infused with FITC-dextran (3 hours after TBI) and counterstained with DAPI (scale bars, 1 mm, representative of 9 brains reviewed). (M) FITC fluorescein intensity of these brains (1-way ANOVA). (N) Plasma levels of endothelial EVs (CD31⁺/VWF⁺) in TBI mice receiving A2 or TBST and sham mice (n = 21, 1-way ANOVA).