Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Brad Lang Thesis.pdf (6.98 MB)

ETD Abstract Container

Abstract Header

THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY

Lang, Bradley Thomas
http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
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.
Heather Broihier (Committee Chair)
Jerry Silver (Advisor)
Lynn Landmesser (Committee Member)
Paul Tesar (Committee Member)
212 p.
Biology; Biomedical Research; Neurobiology; Neurology; Neurosciences
Spinal Cord Injury; Regenerative Medicine; Chondroitin Sulfate Proteoglycans; PTPsigma; Protein Tyrosine Phosphatase Sigma; Receptor Protein Tyrosine Phosphatase Sigma; Axonal Regeneration; Axonal Plasticity; Glial Scar

Recommended Citations

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)

case1417619755
1,272
© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.