Recombinant GDF11 Improves Neurological Recovery in Models of Hemorrhagic Stroke and Traumatic Brain Injury
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Background
Intracerebral hemorrhage (ICH) and traumatic brain injury (TBI) are leading causes of long-term neurological disability and mortality worldwide, with no approved therapies that promote functional recovery. Growth differentiation factor 11 (GDF11), a circulating TGFβ-family protein, has shown regenerative and neurorestorative potential in models of ischemic stroke.
Methods
We evaluated recombinant GDF11 (rGDF11) in mouse models of ICH and TBI. ICH was induced by intrastriatal collagenase injection, and neurological recovery was assessed using Neuroseverity Score (NSS), Rotarod (RR), and CatWalk (CW) analyses up to 28 days post-injury. Histological assessments of vascularization, neuronal density, and microglial/macrophage density were performed 28 days after ICH. For TBI, a closed-head injury model using a pneumatic impactor was employed, and NSS and RR assessments were conducted through 28 days post-injury.
Results
rGDF11 treatment significantly improved neurobehavioral performance following ICH, including NSS, RR, and CW parameters (forelimb base of support and average speed). Histological analyses revealed enhanced vascular area and neuronal density, with reduced microglial/macrophage density in rGDF11-treated mice. Following TBI, rGDF11 accelerated functional recovery, improving RR latency by day 6 and NSS by day 28 post-injury.
Conclusion
rGDF11 promotes structural and functional recovery after both hemorrhagic and traumatic brain injury in mice. These findings, together with prior evidence in ischemic stroke, support rGDF11 as a promising neurorestorative biologic with broad therapeutic potential for diverse forms of brain injury.
