EXPERIMENTAL OPTIC NEURITIS--OXIDATIVE INJURY

Project: Research project

Description

Optic neuritis is a major cause of visual loss in healthy young adults and
the first sign of multiple sclerosis in 80% of such patients. Disruption
of the blood-brain barrier plays a paramount role in the pathophysiology of
this autoimmune disorder of demyelination. Our recent studies in a closely
related guinea pig model of reliable and reproducible immune-mediated
demyelination suggest reactive oxygen metabolites, discharged by
macrophages,make an important contribution to altered permeability of the
blood-brain barrier and destruction of the myelin sheath. Based on these preliminary observations, we propose a hypothesis that
reactive oxygen (free radical) induced disruption of the blood-brain
barrier is the initial tissue alteration contributing to lipid peroxidation
of myelin an demyelination of the optic nerve. In order to test this
hypothesis and explore the potential for treatment with antioxidants and
free radical scavengers, we will perform the following studies: (1) Assessment of endogenous production of reactive oxygen species and
their relationship t blood-brain barrier permeability, by ultrastructural,
histochemical localization of hydrogen peroxide in an animal model of optic
nerve demyelination. (2) Suppression of altered vascular permeability induced by disruption of
the blood-brain barrier and myelin peroxidation by hydrogen peroxide and
reactive oxygen metabolites derived from hydrogen peroxide in experimental
demyelination of the optic nerve, by exogenous administration of
antioxidants and free radical scavengers. (3) Assessment of sequential stages in the disruption of the blood-brain
barrier by study of magnetic resonance imaging of gadolinium leakage in the
optic nerve and the effect of hydrogen peroxide detoxification in
suppressing these alterations of vascular permeability during initial and
chronic phases of experimental allergic encephalomyelitis.
StatusFinished
Effective start/end date5/1/908/31/13

Funding

  • National Institutes of Health: $221,691.00
  • National Institutes of Health: $290,000.00
  • National Institutes of Health: $239,779.00
  • National Institutes of Health: $375,418.00
  • National Institutes of Health: $290,000.00
  • National Institutes of Health
  • National Institutes of Health: $389,423.00
  • National Institutes of Health: $290,000.00
  • National Institutes of Health: $160,498.00
  • National Institutes of Health: $291,000.00
  • National Institutes of Health: $360,330.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $379,283.00

Fingerprint

Optic Neuritis
Genetic Therapy
Demyelinating Diseases
Optic Nerve
Hydrogen Peroxide
Autoimmune Experimental Encephalomyelitis
Blood-Brain Barrier
Myelin Sheath
Multiple Sclerosis
Reactive Oxygen Species
Capillary Permeability
Permeability
Oxygen
Animal Models
Free Radical Scavengers
Free Radicals
Magnetic Resonance Imaging
Gadolinium
Young Adult
Wounds and Injuries

ASJC

  • Medicine(all)