Abstract Body: Abstract: Growth differentiation factor 11 (GDF11), a member of the TGFβ superfamily, has emerged as a promising therapeutic candidate for stroke recovery, due to its roles in promoting tissue regeneration, new blood vessel formation, neurogenesis, and anti-inflammatory responses. This study investigates the effects of recombinant GDF11 (rGDF11) on serum biomarkers in a rat model of ischemic stroke (IS), aiming to identify biomarkers that can support the clinical application of GDF11-based therapies.
Hypothesis: We propose that blood, which contains proteins secreted from various tissues, can reveal biomarkers that elucidate rGDF11's mechanisms of action in stroke recovery and support its clinical development.
Methods: Male Sprague-Dawley rats (8–10 weeks old) with ischemic brain injury, induced by permanent middle cerebral artery occlusion (pMCAO), received intravenous rGDF11 injections starting 24 hours after injury. Recovery was assessed using limb placement and body swing tests. Serum samples were collected at multiple time points, with biomarker analysis conducted via ELISA and further profiling performed using the SomaScan Assay.
Results: Behavioral testing confirmed improvements in sensorimotor functions. ELISA analysis of serum samples detected an acute-phase protein that increased after stroke and decreased following rGDF11 treatment. SomaScan profiling identified a range of stroke-related proteins responsive to rGDF11, offering a view of potential recovery pathways. Protein data from days 2, 3, and 5 suggested enhanced angiogenesis, neurogenesis, axon growth, and synapse development, along with reduced neuroinflammation.
Conclusions: rGDF11 shows potential as a neurorestorative treatment for ischemic stroke. This study identifies potential pharmacodynamic and mechanistic biomarkers that could facilitate the clinical translation of GDF11-based therapies.