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Cell Based Therapy Reduces Secondary Damage and Increases Extent of Microglial Activation Following Cortical Injury
Author(s) -
Orczykowski Mary E,
Calderazzo Samantha M,
Shobin Eli,
Pessina Monica A,
Oblak Adrian L,
Finklestein Seth P,
Kramer Brian C,
Mortazavi Farzad,
Rosene Douglas L,
Moore Tara L
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb166
Subject(s) - microglia , white matter , oxidative stress , myelin , reactive oxygen species , cytotoxic t cell , cerebral cortex , brain damage , lesion , lipid peroxidation , chemistry , pathology , inflammation , medicine , neuroscience , central nervous system , biology , immunology , biochemistry , in vitro , magnetic resonance imaging , radiology
Cortical injury elicits long‐term cytotoxic and cytoprotective mechanisms within the brain and the balance of these pathways can determine the functional outcome for the individual. Cytotoxicity is exacerbated by production of reactive oxygen species, accumulation of iron, and peroxidation of cell membranes and myelin. There are currently no neurorestorative treatments to aid in balancing the cytotoxic and cytoprotective mechanisms following cortical injury. Cell based therapies are an emerging treatment that may function in immunomodulation, reduction of secondary damage, and reorganization of surviving structures. We previously evaluated human umbilical tissue‐derived cells (hUTC) in our non‐human primate model of cortical injury restricted to the hand area of primary motor cortex. Systemic hUTC treatment resulted in significantly greater recovery of fine motor function compared to vehicle controls. Here we investigate the hypothesis that hUTC treatment reduces oxidative damage and iron accumulation and increases the extent of the microglial response to cortical injury. To test this, brain sections from these monkeys were processed using immunohistochemistry to quantify oxidative damage (4‐HNE) and activated microglia (LN3), and Prussian Blue to quantify iron. hUTC treated subjects exhibited significantly reduced oxidative damage in the sublesional white matter and iron accumulation in the perilesional area as well as a significant increase in activated microglia along downstream white matter. Increased perilesional iron accumulation was associated with greater perilesional oxidative damage and larger reconstructed lesion volume. These findings support the hypothesis that systemic hUTC administered 24 hours after cortical damage decreases the cytotoxic response while increasing the extent of microglial activation. Support or Funding Information This study was supported by a contract from Advanced Technologies and Regenerative Medicine (ATRM), LLC. [RR# 101115‐PR] who provided the cell therapy product and the vehicle control and by the National Institutes of Health [NIH‐NINDS R21NS081261]. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .