Abstract Body: Introduction: Intracranial hemorrhage (ICH) and traumatic brain injury (TBI) are severe neurological conditions with different causes but similar consequences, such as brain tissue damage, elevated intracranial pressure, and impaired neurological function. TBI typically arises from external trauma, while ICH usually stems from vascular issues. Despite their prevalence, no effective neurorestorative treatments exist for either condition. Recent studies suggest that Growth Differentiation Factor 11 (GDF11), a member of the TGFβ family, may aid brain recovery through mechanisms like neovascularization and anti-inflammatory effects. Here we explore the therapeutic potential of recombinant GDF11 (rGDF11) in enhancing recovery in rodent models of ICH and TBI.
Methods: Sensorimotor recovery was assessed in mouse models of ICH and TBI. In the ICH model, intrastriatal collagenase injections were performed as described by Lei et al., 2014. For TBI, the murine closed head injury model with a pneumatic impactor was used, following Laskowitz et al., 2017. Mice received intraperitoneal injections of rGDF11 or a vehicle post injury. Behavioral assessments, including NeuroSeverity Score (NSS) and Rotarod Latency (RR) were performed pre- and post-injury. Immunohistochemical analysis was conducted 28 days post-ICH to examine vascularization (Cd31) and microglia density (F4/80).
Results: rGDF11 treatment significantly improved behavioral outcomes following ICH and TBI compared to the vehicle group. In the ICH model, rGDF11 improved NSS at 21 and 28 days and RR at 14 and 28 days post-injury. Treated mice also exhibited faster gait speeds and narrower forelimb base of support 7 days after injury, indicating enhanced locomotor function. Similar improvements in sensorimotor function were observed in the TBI model. Histological analyses revealed that rGDF11 increased vascularization and reduced microglial density in the brain 28 days after ICH.
Conclusions: rGDF11 shows strong potential as a neurorestorative therapy for ICH and TBI. Its ability to improve motor and behavioral outcomes highlights its promise in promoting recovery through mechanisms such as neovascularization and anti-inflammatory effects, which are essential for brain repair and functional recovery.