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Neurotrophic Factor-Laden Acellular Chondroitin Sulfate Scaffolds Promote Chronic Functional Recovery After Severe Traumatic Brain Injury

View ORCID ProfileCharles-Francois V. Latchoumane, View ORCID ProfileMartha I. Betancur, View ORCID ProfileGregory A. Simchick, View ORCID ProfileMin Kyoung Sun, View ORCID ProfileRameen Forghani, View ORCID ProfileChristopher E. Lenear, View ORCID ProfileAws Ahmed, View ORCID ProfileRamya Mohankumar, Nivedha Balaji, View ORCID ProfileHannah D. Mason, Philip V. Holmes, View ORCID ProfileQun Zhao, Ravi V. Bellamkonda, View ORCID ProfileLohitash Karumbaiah
doi: https://doi.org/10.1101/2020.06.21.116970
Charles-Francois V. Latchoumane
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
2Edgar L. Rhodes Center for ADS, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, 30602, USA
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  • ORCID record for Charles-Francois V. Latchoumane
Martha I. Betancur
3Department of Biomedical Engineering, Pratt School of Engineering, Duke University, 101 Science Drive, Durham, NC, 27705 USA
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  • ORCID record for Martha I. Betancur
Gregory A. Simchick
4Department of Physics and Astronomy, University of Georgia, Athens, GA, 30602, USA
5Bio-Imaging Research Center, University of Georgia, Athens, GA, 30602, USA
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Min Kyoung Sun
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
6Division of Neuroscience, Biomedical & Health Sciences Institute, University of Georgia, Athens, GA 30602, USA
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Rameen Forghani
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
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  • ORCID record for Rameen Forghani
Christopher E. Lenear
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
2Edgar L. Rhodes Center for ADS, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, 30602, USA
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Aws Ahmed
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
2Edgar L. Rhodes Center for ADS, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, 30602, USA
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Ramya Mohankumar
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
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Nivedha Balaji
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
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Hannah D. Mason
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
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Philip V. Holmes
6Division of Neuroscience, Biomedical & Health Sciences Institute, University of Georgia, Athens, GA 30602, USA
7Psychology Department, University of Georgia, Athens, GA, 30602, USA
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Qun Zhao
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
4Department of Physics and Astronomy, University of Georgia, Athens, GA, 30602, USA
5Bio-Imaging Research Center, University of Georgia, Athens, GA, 30602, USA
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Ravi V. Bellamkonda
3Department of Biomedical Engineering, Pratt School of Engineering, Duke University, 101 Science Drive, Durham, NC, 27705 USA
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Lohitash Karumbaiah
1Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA
2Edgar L. Rhodes Center for ADS, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, 30602, USA
6Division of Neuroscience, Biomedical & Health Sciences Institute, University of Georgia, Athens, GA 30602, USA
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  • For correspondence: lohitash@uga.edu
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ABSTRACT

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 Statement

The authors have declared no competing interest.

Footnotes

  • 1. Minor mismatch for figure citation in text: Result section: p5: Fig 7A-C and E -> Sup Fig 6A-C and E p5: Sup Fig 8E -> Sup Fig 7E p6: Fig 6D -> Fig 5D p7: Fig2 -> Fig4 2. Missing Scale bars and Labels in Fig 1C and E 3. Figure Miss Label: Fig 5C-D 4. Missing Figure caption (Fig 5E-F) 5. Missing Figure Label: Sup Fig 11F 6. Minor typos and Grammar fixes 7. Authors middle initial and ORCID added 8. Mislabeling Methods: T2WI

  • https://doi.org/10.17632/47fzn6nt4m.1

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Neurotrophic Factor-Laden Acellular Chondroitin Sulfate Scaffolds Promote Chronic Functional Recovery After Severe Traumatic Brain Injury
Charles-Francois V. Latchoumane, Martha I. Betancur, Gregory A. Simchick, Min Kyoung Sun, Rameen Forghani, Christopher E. Lenear, Aws Ahmed, Ramya Mohankumar, Nivedha Balaji, Hannah D. Mason, Philip V. Holmes, Qun Zhao, Ravi V. Bellamkonda, Lohitash Karumbaiah
bioRxiv 2020.06.21.116970; doi: https://doi.org/10.1101/2020.06.21.116970
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Neurotrophic Factor-Laden Acellular Chondroitin Sulfate Scaffolds Promote Chronic Functional Recovery After Severe Traumatic Brain Injury
Charles-Francois V. Latchoumane, Martha I. Betancur, Gregory A. Simchick, Min Kyoung Sun, Rameen Forghani, Christopher E. Lenear, Aws Ahmed, Ramya Mohankumar, Nivedha Balaji, Hannah D. Mason, Philip V. Holmes, Qun Zhao, Ravi V. Bellamkonda, Lohitash Karumbaiah
bioRxiv 2020.06.21.116970; doi: https://doi.org/10.1101/2020.06.21.116970

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