Neuroprotection by Progesterone through Stimulation of Mitochondrial Gene Expression

Abstract

In year I of this grant, we have made good progress toward meeting our stated objectives. For Objective I, we have; A. established that administration of kainic acids to rats at a dose of 8.5 mg/kg results in consistent and reliable seizure behavior and that survival times of 96 hr post-injection is optimal for detection of brain injury and B. established that progesterone can protect animals from seizures produced by kainate, and that a relatively low dose of progesterone is effective in conveying this effect. In addition, we are beginning studies to examine the effects of co-administration of estrogen on the neuroprotective effects of progesterone. For Objectives 2 and 3, we have; established that transient (30 min) exposure to glutamate (100 micrometer) produced reliable and consistent neuronal death after 24 hr. Furthermore, our studies have established that addition of progesterone does not protect rat cerebellar neurons against glutamate-induced excitotoxic neuronal death. We are extending these studies to cultures of cortical neurons that may possess more progesterone receptors, and are beginning to examine the effects of estrogen and co-administration of estrogen and progesterone on glutamate-induced excitotoxicity.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2000
Accession Number
ADA389018

Entities

People

  • Gary Fiskum

Organizations

  • University of Maryland, Baltimore

Tags

DTIC Thesaurus Topics

  • Antigens
  • Brain
  • Brain Injuries
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Culture Techniques
  • Detection
  • Epilepsy
  • Estrogens
  • Gene Expression
  • Glutamates
  • Hormones
  • Nervous System
  • Survival

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Neuroscience