Multifaceted Benefits of GDF11 Treatment in Spinal Cord Injury: In Vitro and In Vivo Studies

Traumatic spinal cord injury (SCI) initiates a series of cellular and molecular events that include both primary and secondary injury cascades. This secondary cascade provides opportunities for the delivery of therapeutic intervention. Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-beta (TGF-beta) superfamily, regulates various biological processes in mammals. The effects of GDF11 in the nervous system were not fully elucidated. Here, we perform extensive in vitro and in vivo studies to unravel the effects of GDF11 on spinal cord after injury. In vitro culture studies showed that GDF11 increased the survival of both neuronal and oligodendroglial cells but decreased microglial cells. In stressed cultures, GDF11 effectively inhibited LPS stimulation and also protected neurons from ischemic damage. Intravenous GDF11 administration to rat after eliciting SCI significantly improved hindlimb functional restoration of SCI rats. Reduced neuronal connectivity was evident at 6 weeks post-injury and these deficits were markedly attenuated by GDF11 treatment. Furthermore, SCI-associated oligodendroglial alteration were more preserved by GDF11 treatment. Taken together, GDF11 infusion via intravenous route to SCI rats is beneficial, facilitating its therapeutic application in the future.

Automated summary

Traumatic spinal cord injury (SCI) triggers a series of cellular and molecular events, leading to both primary and secondary injury cascades. The secondary cascade provides an opportunity for therapeutic intervention, and in this study, the effects of Growth differentiation factor 11 (GDF11) on spinal cord injury were investigated. The results showed that GDF11 increased the survival of neuronal and oligodendroglial cells and decreased microglial cells. In addition, GDF11 protected neurons from ischemic damage and improved hindlimb functional restoration in SCI rat models. These findings suggest that GDF11 infusion could be a beneficial therapeutic approach for SCI in the future.