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Brad Lang Thesis.pdf (6.98 MB)
ETD Abstract Container
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THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY
Author Info
Lang, Bradley Thomas
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755
Abstract Details
Year and Degree
2015, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Abstract
Contusive spinal cord injury (SCI) is a devastating condition that leads to permanent disability due to the lack of neuronal regeneration and functional plasticity. It is well established that an upregulation of glial derived chondroitin sulfate proteoglycans (CSPGs) within the scar creates a barrier to axonal regrowth. Additionally, CSPGs in the perineuronal net (PNN) distal to the injury site prevent remodeling of spared pathways that could provide functional recovery. Protein tyrosine phosphatase-sigma (PTPs), along with its sister phosphatase leukocyte common antigen-related (LAR), and the Nogo receptors 1 and 3 (NgRs) have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. We found that PTPs plays a critical role in converting growth cones into a stabilized dystrophic state within CSPG gradients. Furthermore, we identified a critical regulatory wedge domain within the first intracellular phosphatase repeat of PTPs. In vitro, a peptide mimetic of this wedge bound to PTPs and released CSPG inhibition. In vivo, we utilized this peptide as a daily systemic treatment to prevent inhibition and promote axonal growth following SCI. This treatment paradigm induced functional recovery of both locomotor and bladder systems, and restored a large volume of serotonergic innervation to the caudal spinal cord below the level of the lesion. Our results provide strong validation of the critical role of PTPs in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.
Committee
Heather Broihier (Committee Chair)
Jerry Silver (Advisor)
Lynn Landmesser (Committee Member)
Paul Tesar (Committee Member)
Pages
212 p.
Subject Headings
Biology
;
Biomedical Research
;
Neurobiology
;
Neurology
;
Neurosciences
Keywords
Spinal Cord Injury
;
Regenerative Medicine
;
Chondroitin Sulfate Proteoglycans
;
PTPsigma
;
Protein Tyrosine Phosphatase Sigma
;
Receptor Protein Tyrosine Phosphatase Sigma
;
Axonal Regeneration
;
Axonal Plasticity
;
Glial Scar
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Citations
Lang, B. T. (2015).
THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755
APA Style (7th edition)
Lang, Bradley.
THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY .
2015. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755.
MLA Style (8th edition)
Lang, Bradley. "THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY ." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755
Chicago Manual of Style (17th edition)
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Document number:
case1417619755
Download Count:
1,322
Copyright Info
© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.