This is a revised submission of a request for continuation of a project aimed at studying functional recovery of penile and external anal sphincter ('sacral') spinal cord reflexes after contusion injuries in rats meant to model human spinal cord injury (SCI). Recovery of sacral reflexes was compared to recovery of locomotion. Serotonergic (5-HT) descending systems are thought to be involved in this recovery, and in the previous funding period, evidence was provided for denervation and reinnervation of sacral MNs by 5-HT after SCI. The source of the 5-HT sprouting is thought to be the small number of axons that remain in the spared rim of fibers after severe contusion SCI. We have shown that glial restricted precursor cells (GRPs) can be transplanted into contusion injuries, and that they alter the lesion environment by reducing glial scarring. The revised submission focuses on the hypothesis that the transplantation of GRPs into the contusion lesion cavity after SCI will result in more 5-HT sprouting and will enhance the recovery of sacral reflexes and locomotion.
In aim 1, we will compare the long-term recovery of sacral and locomotor functions in rats receiving contusion lesions with and without GRP transplants given at 9-10 days following injury.
In aim 2 we will compare the amount of serotonergic input to identified external anal sphincter (EAS) and bulbospongiosis (BS) motoneurons (MNs) in rats with and without GRP transplants.
In aim 3, we will examine the source of the sprouting into the sacral cord by labeling brainstem sources of 5-HT with anterograde tracers combined with 5-HT IHC. This will also allow us to test the hypothesis that the reinnervation of the cord by spared descending systems maintains the specificity of the original connections. These studies represent a collaboration between laboratories studying SCI and developmental biology, and are intended to provide guidance on the possible therapeutic value of glial precursor transplantation in SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031193-11
Application #
6927155
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (01))
Program Officer
Kleitman, Naomi
Project Start
1994-02-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
11
Fiscal Year
2005
Total Cost
$341,094
Indirect Cost
Name
Ohio State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Nielson, Jessica L; Paquette, Jesse; Liu, Aiwen W et al. (2015) Topological data analysis for discovery in preclinical spinal cord injury and traumatic brain injury. Nat Commun 6:8581
Nielson, Jessica L; Guandique, Cristian F; Liu, Aiwen W et al. (2014) Development of a database for translational spinal cord injury research. J Neurotrauma 31:1789-99
Ferguson, Adam R; Irvine, Karen-Amanda; Gensel, John C et al. (2013) Derivation of multivariate syndromic outcome metrics for consistent testing across multiple models of cervical spinal cord injury in rats. PLoS One 8:e59712
Downing, Timothy L; Wang, Aijun; Yan, Zhi-Qiang et al. (2012) Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair. J Control Release 161:910-7
Gensel, John C; Tovar, C Amy; Bresnahan, Jacqueline C et al. (2012) Topiramate treatment is neuroprotective and reduces oligodendrocyte loss after cervical spinal cord injury. PLoS One 7:e33519
Veiga, S; Ly, J; Chan, P H et al. (2011) SOD1 overexpression improves features of the oligodendrocyte precursor response in vitro. Neurosci Lett 503:10-4
Nout, Yvette S; Culp, Esther; Schmidt, Markus H et al. (2011) Glial restricted precursor cell transplant with cyclic adenosine monophosphate improved some autonomic functions but resulted in a reduced graft size after spinal cord contusion injury in rats. Exp Neurol 227:159-71
Sun, Fang; Lin, Chien-Liang Glenn; McTigue, Dana et al. (2010) Effects of axon degeneration on oligodendrocyte lineage cells: dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis. Glia 58:1304-19
Beattie, Michael S; Ferguson, Adam R; Bresnahan, Jacqueline C (2010) AMPA-receptor trafficking and injury-induced cell death. Eur J Neurosci 32:290-7
Nout, Yvette S; Mihai, Georgeta; Tovar, C Amy et al. (2009) Hypertonic saline attenuates cord swelling and edema in experimental spinal cord injury: a study utilizing magnetic resonance imaging. Crit Care Med 37:2160-6

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