A heparan sulfate-based matrix therapy reduces brain damage and enhances functional recovery following stroke.

摘要: Alteration of the extracellular matrix (ECM) is one major events in pathogenesis brain lesions following ischemic stroke. Heparan sulfate mimetics (HSm) are synthetic pharmacologically active polysaccharides that promote ECM remodeling and tissue regeneration various types lesions. HSm bind to growth factors, protect them from enzymatic degradation increase their bioavailability, which promotes repair. As altered during stroke have been shown restore ECM, we investigated potential HSm4131 (also named RGTA-4131®) plasticity after a Methods: Ischemic was induced rats using transient (1 h) intraluminal middle cerebral artery occlusion (MCAo). Animals were assigned treatment (HSm4131; 0.1, 0.5, 1.5, or 5 mg/kg) vehicle control (saline) groups at different times (1, 2.5 6 MCAo. Brain damage assessed by MRI for acute (2 days) chronic (14 phases post-occlusion. Functional deficits evaluated with battery sensorimotor behavioral tests. HSm4131-99mTc biodistribution analyzed between min 3 h reperfusion. distribution cellular reactions, including angiogenesis neurogenesis, immunohistochemistry, factor gene expression (VEGF-A, Ang-2) quantified RT-PCR. Results: HSm4131, administered intravenously induction, located remained hemisphere. conferred long-lasting neuroprotection, significantly reduced functional no alteration physiological parameters. It also restored increased processes, i.e., affected Conclusion: represent promising ECM-based therapeutic strategy repair favor recovery.