Autologous bone marrow mononuclear cells therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.

Supinder S. Bedi, Peter A. Walker, Shinil K. Shah, Fernando Jimenez, Chelsea P. Thomas, Philippa Smith, Robert A. Hetz, Hasen Xue, Shibani Pati, Pramod K. Dash, Charles S. Cox

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Autologous bone marrow-derived mononuclear cells (AMNCs) have shown therapeutic promise for central nervous system insults such as stroke and traumatic brain injury (TBI). We hypothesized that intravenous injection of AMNC provides neuroprotection, which leads to cognitive improvement after TBI. A controlled cortical impact (CCI) rodent TBI model was used to examine blood-brain barrier (BBB) permeability, neuronal and glial apoptosis, as well as cognitive behavior. Two groups of rats underwent CCI with AMNC treatment (CCI-autologous) or without AMNC treatment (CCI-alone), consisting of 2 million AMNC per kilogram body weight harvested from the tibia and intravenously injected 72 hours after injury. CCI-alone animals underwent sham harvests and received vehicle injections. Ninety-six hours after injury, AMNC significantly reduced the BBB permeability in injured animals, and there was an increase in apoptosis of proinflammatory activated microglia in the ipsilateral hippocampus. At 4 weeks after injury, we observed significant improvement in probe testing of CCI-Autologous group in comparison to CCI-Alone in the Morris Water Maze paradigm. Our data demonstrate that the intravenous injection of AMNC after TBI leads to neuroprotection by preserving early BBB integrity, increasing activated microglial apoptosis and improving cognitive function.

Original languageEnglish (US)
Pages (from-to)410-416
Number of pages7
JournalThe journal of trauma and acute care surgery
Volume75
Issue number3
DOIs
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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