Abstract

This revised renewal proposal is to investigate the mechanisms by which certain interventions protect against the cascade of deleterious events that follow a period of spinal ischemia. There are two specific aims. The first is to define the optimal thermal and temporal characteristics of perischemic cooling. Measures of ischemic consequences or correlative changes with protection include spinal extracellular potassium, dorsal horn neuronal activity, amino acid and PGE2 release, neurological outcome at 2-5 days and spinal histopathology.
The second aim i s to define the factors governing spinal expression of HSP72 and immediate early genes, and the correlation of such expression with post-ischemia functional recovery. hsp72, c-fos and c-jun expression will be measured following transient cooling or heating to two different temperatures, intrathecal delivery of substance P; NMDA, AMPA, or kainic acid; high potassium; or either of two transient non-injurious intervals of spinal ischemia. The protective effects of these manipulations will be measured on damage observed with a fixed injurious duration of ischemia delivered at 3 different intervals after the conditioning treatments which induce hsp72 and/or fos/jun expression; measures of damage include neurologic outcome, spinal amino acid and PGE2 release and histopathology. The role of HSP72 expression in protection will be tested by examining the effects of antisense pretreatment on HSP72 expression and the same three measures of ischemic damage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS032794-04A1
Application #
2612316
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Heetderks, William J
Project Start
1994-09-01
Project End
2002-03-31
Budget Start
1998-05-01
Budget End
1999-03-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Marsala, Jozef; Lukacova, Nadezda; Kolesar, Dalibor et al. (2007) The distribution of primary nitric oxide synthase- and parvalbumin- immunoreactive afferents in the dorsal funiculus of the lumbosacral spinal cord in a dog. Cell Mol Neurobiol 27:475-504
Marsala, Jozef; Lukacova, Nadezda; Kolesar, Dalibor et al. (2006) Nitrergic proprioceptive afferents originating from quadriceps femoris muscle are related to monosynaptic Ia-motoneuron stretch reflex circuit in the dog. Cell Mol Neurobiol 26:1387-412
Lukacova, Nadezda; Kolesarova, Maria; Kucharova, Karolina et al. (2006) The effect of a spinal cord hemisection on changes in nitric oxide synthase pools in the site of injury and in regions located far away from the injured site. Cell Mol Neurobiol 26:1367-85
Lukacova, Nadezda; Kolesar, Dalibor; Marsala, Martin et al. (2006) Immunohistochemical, histochemical and radioassay analysis of nitric oxide synthase immunoreactivity in the lumbar and sacral dorsal root ganglia of the dog. Cell Mol Neurobiol 26:17-44
Marsala, Jozef; Lukacova, Nadezda; Sulla, Igor et al. (2005) The evidence for nitric oxide synthase immunopositivity in the monosynaptic Ia-motoneuron pathway of the dog. Exp Neurol 195:161-78
Marsala, Martin (2004) Loop dialysis catheter: a technology for chronic spinal dialysis in a freely moving rat. Methods Mol Med 99:99-108
Carmel, Jason B; Kakinohana, Osamu; Mestril, Ruben et al. (2004) Mediators of ischemic preconditioning identified by microarray analysis of rat spinal cord. Exp Neurol 185:81-96
Cizkova, Dasa; Carmel, Jason B; Yamamoto, Kenji et al. (2004) Characterization of spinal HSP72 induction and development of ischemic tolerance after spinal ischemia in rats. Exp Neurol 185:97-108
Marsala, Jozef; Lukacova, Nadezda; Cizkova, Dasa et al. (2004) Premotor nitric oxide synthase immunoreactive pathway connecting lumbar segments with the ventral motor nucleus of the cervical enlargement in the dog. J Chem Neuroanat 27:43-54
Marsala, Martin; Kakinohana, Osamu; Yaksh, Tony L et al. (2004) Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia. Eur J Neurosci 20:2401-14

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