Delayed treatments for stroke influence neuronal death in rat organotypic slice cultures subjected to oxygen glucose deprivation.

Abstract

A major limitation of current stroke therapies is the need to treat candidate patients within 3 h of stroke onset. Human umbilical cord blood cell (HUCBC) and the sigma receptor agonist 1,3, di-o-tolylguanidine (DTG) administration both caused significant reductions in brain damage in the rat middle cerebral artery occlusion model of stroke when administered at delayed timepoints. In vivo, these treatments suppress the infiltration of peripheral lymphocytes into the brain in addition to decreasing neurodegeneration. An ex vivo organotypic slice culture (OTC) model was utilized to characterize the efficacy of these treatments in mitigating neurodegeneration in ischemic brain tissue in the absence of the peripheral immune system. Slice cultures subjected to oxygen glucose deprivation (OGD) had significantly elevated levels of degenerating neurons and microglial nitric oxide production when compared to their normoxic counterparts. In cultures subjected to OGD, HUCBC but not DTG treatment reduced the number of degenerating neurons and the production of microglial derived nitric oxide back to levels detected in normoxic controls. These data show that HUCBC treatment can mediate direct neuroprotection and suppress innate inflammation in ischemic brain tissue in the absence of the peripheral immune system, whereas DTG requires peripheral effects to mediate neuroprotection. These experiments yield insight into the mechanisms by which these neuroprotective treatments function at delayed timepoints following stroke.

• Authors: A A Hall, C C Leonardo, L A Collier, D D Rowe, A E Willing, K R Pennypacker
• Journal: Neuroscience (Neuroscience) Vol. 164 Issue 2 Pg. 470-7 (Dec 01 2009) ISSN: 1873-7544 [Electronic] United States
• PMID: 19723565 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Guanidines
• Receptors, sigma
• Nitric Oxide
• Glucose
• 1,3-ditolylguanidine

Topics

• Animals
• Brain (drug effects, physiopathology)
• Brain Ischemia (drug therapy, physiopathology, therapy)
• Cell Hypoxia (drug effects, physiology)
• Cord Blood Stem Cell Transplantation
• Disease Models, Animal
• Female
• Glucose (deficiency, metabolism)
• Guanidines (pharmacology)
• Humans
• In Vitro Techniques
• Male
• Microglia (drug effects, physiology)
• Nerve Degeneration (drug therapy, physiopathology, therapy)
• Neurons (drug effects, physiology)
• Nitric Oxide (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, sigma (agonists)
• Stroke (drug therapy, physiopathology, therapy)
• Time Factors