MARKERS OF CNS INJURY

Project: Research project

Description

This proposal explores expression of the rapidly inducible c-fos and heat
shock genes following neural injury. Molecular mechanisms of injury are
poorly understood and new indicators of injury are needed since many animal
studies use histological stains to assess the efficacy of therapeutic drug
regimens for ameliorating the CNS damage caused by stroke, excitotoxins,
and head injury. Many histological stains have serious limitations
including problems detecting early injury, particularly to single cells. Fos, the gene product of c-fos, is rapidly induced in the nuclei of single
cells throughout cortex and amygdala following focal cortical lesions and
focal cortical injections of NGF. Experiments will test the hypothesis
that local release of NGF and other molecules at the sites of injury
activate cholinergic neurons in the nucleus Basalis of Meynert (NBM) which
in turn project upon and induce Fos in cells throughout cortex. We will
determine (a) which cells express Fos and (b) which trophic substances,
when injected into cortex or into NBM, induce Fos, detected
immunocytochemically, and c-fos mRNA, detected using Northern blots and in
situ hybridization. Heat shock proteins (HSPs) are also rapidly expressed following injury.
Stroke, diffuse forebrain ischemia, systemic and local injections of kainic
acid, and local injections of kynurenic acid and MK801 rapidly induce the
heart shock protein, HSP72, in single neurons and glia. The time course
and topographic distribution of HSP72 induction following ischemic injury
will be described. This will be correlated with the regions where cell
death or cell survival occurs on standard histological stains. The
induction of HSP72 produced by excitatory amino acid agonists and
antagonists will be studied in primary cultures of neurons and glia.
Moreover, experiments will test whether induction of HSP72 proteins
protects cultured neurons and glia from otherwise lethal injuries. Future
studies will determine whether prior induction of either the heat shock or
c-fos genes protects the brain from injury.
StatusFinished
Effective start/end date6/1/905/31/08

Funding

  • National Institutes of Health: $262,820.00
  • National Institutes of Health: $351,357.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $234,391.00
  • National Institutes of Health
  • National Institutes of Health: $352,688.00
  • National Institutes of Health
  • National Institutes of Health: $255,166.00
  • National Institutes of Health: $359,219.00
  • National Institutes of Health
  • National Institutes of Health: $364,563.00
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Wounds and Injuries
Heat-Shock Proteins
fos Genes
Brain
Brain Ischemia
Ischemia
Proteins
Neuroglia
Neurons
Stroke
Basal Nucleus of Meynert
Genes
Recombinant Proteins
Cerebrovascular Circulation
Coloring Agents
Shock
Gerbillinae
Nerve Growth Factor
Heme Oxygenase (Decyclizing)
Hypoxia-Inducible Factor 1

ASJC

  • Medicine(all)
  • Neuroscience(all)