Brain recovery mediated by toll-like receptor 4 in rats after intracerebral hemorrhage

• TLR4 levels were significantly higher in the ICH group than in the Sham group.
• By 14 d, the ICH group showed significantly higher levels of VEGF, BDNF, and MMP-9.
• Administering TAK-242 blocked these increase.
• TLR4 may promote brain repair in the late phase of ICH.

Activation of the immune system via toll-like receptor 4 (TLR4) is implicated in both negative and positive processes in the central nervous system, including inflammation and angiogenesis. Whether TLR4 also participates in brain recovery following intracerebral hemorrhage (ICH) has not been investigated. We used the rat model of collagenase-induced ICH to determine whether TLR4 acts as a key regulator of brain recovery in the late phase of injury. After ICH, TLR4 levels in the ipsilateral striatum were significantly higher in the ICH group than in the Sham group on days 1, 3, 7 and 14 after ICH induction. By 14 d, the ICH group showed significantly higher levels of vascular endothelial growth factor, brain-derived neurotrophic factor, and MMP-9 than the Sham group, as well as greater numbers of vessels and BrdU- and DCX-positive cells. All these ICH-induced increases were significantly smaller in the TAK-242 group. The TLR4 antagonist also inhibited the recovery of neurological function after ICH. A TLR4 antagonist reduced ICH-induced neurogenesis and angiogenesis in a rat. These findings suggest that TLR4 may promote brain repair in the late phase of ICH.