RT Journal Article
SR Electronic
T1 Neurotrophic Factor-Laden Acellular Chondroitin Sulfate Scaffolds Promote Chronic Functional Recovery After Severe Traumatic Brain Injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.21.116970
DO 10.1101/2020.06.21.116970
A1 Charles-Francois V. Latchoumane
A1 Martha I. Betancur
A1 Gregory A. Simchick
A1 Min Kyoung Sun
A1 Rameen Forghani
A1 Christopher E. Lenear
A1 Aws Ahmed
A1 Ramya Mohankumar
A1 Nivedha Balaji
A1 Hannah D. Mason
A1 Philip V. Holmes
A1 Qun Zhao
A1 Ravi V. Bellamkonda
A1 Lohitash Karumbaiah
YR 2020
UL http://biorxiv.org/content/early/2020/07/07/2020.06.21.116970.abstract
AB Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain’s poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely post-sTBI, significantly enhanced cellular repair and gross motor function recovery when compared to controls, 20 weeks post-sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations, demonstrated the significant recovery of ‘reach-to-grasp’ function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely post-sTBI can support complex cellular, vascular, and neuronal circuit repair, chronically after sTBI.Competing Interest StatementThe authors have declared no competing interest.