Treadmill rehabilitation treatment enhanced BDNF-TrkB but not NGF-TrkA signaling in a mouse intracerebral hemorrhage model

Intracerebral hemorrhage (ICH), accounting for 15-20% of strokes, can cause significant brain injury and life long neurological deficits. We investigated whether treadmill exercise rehabilitation could improve brain repair after ICH and whether involvement of NFG-TrkA and BDNF-TrkB signaling could be observed during repair period in an experimental mouse ICH model reproduced by heparinized-collagenase infusion into the left caudate putamen. 5-Bromo-2-deoxyuridine (BrdU) labeled new dividing cell can be observed clearly around the injured cortex and striatum region on day 7 (D7) after operation, and both TrkA and TrkB neurotropic receptors were activated. A subgroup of these ICH mice began the treadmill exercise from D4 after operation. Then we found that the overall immunofluorescent signals of p-Y490-TrkA and p-Y705-TrkB were both decreased in all groups at D14 after operation. However, compared to the non-exercise ICH group mouse, the immunofluorescent intensity of BDNF and p-Y705-TrkB were significantly higher in the exercise group. In addition, there was no difference in p-Y490-TrkA. Our results suggest that BDNF-TrkB but not NGF-TrkA signaling is involved in the brain repair after ICH, and early proper treadmill exercise might promote this repair process.

► We investigated the activation of NGF-TrkA and BDNF-TrkB signaling in a hemorrhage mouse model. ► NGF-TrkA and BDNF-TrkB signaling may play the neuroprotection role after ICH injury. ► Neurogenesis presented in the peri-hemorrhagic area on D7 after the ICH operation. ► Neurotrophins-Trk receptor signaling is involved in the process of brain repair. ► BDNF-p-Y705-TrkB signaling pathway is enhanced by early treadmill exercise after ICH operation.