Early pharmacological intervention in acute spinal cord injury (SCI) is based on the premise that secondary injury following the initial insult contributes to ultimate spinal cord damage and neurologic deficit. This contention is strengthened by the recent observation of the Second National Acute Spinal Cord Injury Studies (NASCIS II) showing that high dose methylprednisolone given within 8 hours of injury improved neurologic recovery in patients with acute SCI. Progressive vascular injury after SCI contributes to secondary injury. Vascular injury is a prominent feature in acute inflammation. All the cardinal features of acute inflammation including deposition of acute inflammatory cells, accumulation of inflammatory mediators, endothelial damage leading to increased vascular permeability and edema formation have been noted in the injured cord. We will continue to explore the vascular mechanism of secondary injury focusing on post-traumatic inflammatory reaction in the pathogenesis of progressive vascular injury. The main theme of this proposal will be on the kininogen-kinin system and eicosanoid profile. The roles of cellular and humoral factors of inflammation relevant to kinin-eicosanoid cascade will be studied in depth to explore cellular and molecular mechanism of progressive vascular injury in the context of a post-traumatic inflammatory reaction. New therapeutic regimens will also be designed based on these studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031767-04
Application #
2460556
Study Section
Neurology A Study Section (NEUA)
Program Officer
Heetderks, William J
Project Start
1994-08-01
Project End
1999-01-31
Budget Start
1997-08-01
Budget End
1999-01-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Neurology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Bennion, Beau; Dasgupta, Somsankar; Hogan, Edward L et al. (2007) Characterization of novel myelin components 3-O-acetyl-sphingosine galactosylceramides by electrospray ionization Q-TOF MS and MS/CID-MS of Li+ adducts. J Mass Spectrom 42:598-620
Dasgupta, Somsankar; Levery, Steven B; Hogan, Edward L (2002) 3-O-acetyl-sphingosine-series myelin glycolipids: characterization of novel 3-O-acetyl-sphingosine galactosylceramide. J Lipid Res 43:751-61
Tyor, William R; Avgeropoulos, Nicholas; Ohlandt, George et al. (2002) Treatment of spinal cord impact injury in the rat with transforming growth factor-beta. J Neurol Sci 200:33-41
Ray, S K; Matzelle, D D; Wilford, G G et al. (2001) Cell death in spinal cord injury (SCI) requires de novo protein synthesis. Calpain inhibitor E-64-d provides neuroprotection in SCI lesion and penumbra. Ann N Y Acad Sci 939:436-49
Dasgupta, S; Hogan, E L (2001) Chromatographic resolution and quantitative assay of CNS tissue sphingoids and sphingolipids. J Lipid Res 42:301-8
Dasgupta, S; van Halbeek, H; Spicer, S et al. (2000) Molecular characterization and immunohistochemical localization of IV(4)GalNAcGgOse(4)Cer: a naturally occurring novel neutral glycosphingolipid in bovine brain. Glycobiology 10:9-Jan
Li, Z; Tyor, W R; Xu, J et al. (1999) Immunohistochemical localization of kininogen in rat spinal cord and brain. Exp Neurol 159:528-37
Bhat, N R; Zhang, P; Lee, J C et al. (1998) Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures. J Neurosci 18:1633-41
Zhang, P; Hogan, E L; Bhat, N R (1998) Activation of JNK/SAPK in primary glial cultures: II. Differential activation of kinase isoforms corresponds to their differential expression. Neurochem Res 23:219-25
Bhat, N R; Zhang, P; Hogan, E L (1995) Thrombin activates mitogen-activated protein kinase in primary astrocyte cultures. J Cell Physiol 165:417-24