Targeting PD-L1 in Traumatic Brain Injury

TBI damages the BBB, enabling recruitment of circulating immune cells, such as M/Mɸ, neutrophils, and activated T cells to the injured site. We also took advantage of the injury-induced transient breakdown of the BBB to study whether administration of PD-L1 blocking antibody (Ab) via subcutaneous (SC) injection could reach the injured site of the brain to exert its blocking function. Previous studies have shown that a single dose of anti-PD-L1 Ab (50 μg/kg or 200 μg/kg) via intravenous or intraperitoneal injection can significantly affect stroke outcome through regulating CNS inflammation [37 (link), 38 (link)]. In our study, mice at 24 h post-TBI were subcutaneously injected with either PD-L1 blocking Ab (ab233482, Abcam, Cambridge, MA), PD-L1-Alex 647-conjugated Ab (ab224030, Abcam, Cambridge, MA), or an irrelevant IgG Ab as a control at 200 μg/kg in 100 μL PBS. PD-L1-Alex 647-conjugated Ab was used for histological examination of Ab penetration into the brain, while PD-L1 blocking Ab was used to study the PD-L1 function in the brain. The treatments were blinded to researchers who performed histological evaluations, behavior tests, and flow cytometry.