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.
|Number of pages||8|
|State||Published - Dec 1 2009|
Bibliographical noteFunding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke (RO 1-NS052839-03 to K.R.P. and A.E.W.; 5R21NS060907 to K.R.P. and A.E.W.) and the American Heart Association (0715096B to A.A.H.). We would also like to acknowledge Karen Lai M.S. for her contributions with image analysis. AEW is an inventor on multiple cord blood patents. She consults to Saneron CCEL Therapeutics, Inc. which has licensed the cord blood technology from the University of South Florida.
- human umbilical cord blood cells
- sigma receptors
ASJC Scopus subject areas
- Neuroscience (all)