Abstract W P94: Autologous Bone Marrow Derived Mononuclear Cells Attenuate Cerebral Edema and Inflammation in Intracerebral Hemorrhage
Background: Autologous bone marrow derived mononuclear cells (MNCs) improve functional recovery after ischemic stroke in rodent models. We now investigate the therapeutic effects of MNCs in intracerebral hemorrhage (ICH) and explore if MNCs impact the post-ICH inflammatory response.
Methods: ICH was induced by stereotaxic infusion of 70 ul autologous whole blood into the left striatum in young male Long Evans rats. At 24 hrs after ICH, rats were randomized to receive an intravenous administration of autologous MNCs (10 million cell/kg) or saline. MNCs were isolated from the bone marrow harvest of the tibias at 22 hrs after ICH without causing limb impairment. A separate sham control group underwent the same surgical procedures but without the blood injection and the aspiration of bone marrow. At 3 days after randomization, brains were harvested to measure cerebral edema and various markers of inflammation in the perihematomal area.
Results: Compared to the saline treated controls, MNCs significantly decreased brain water content in the ipsilateral hemisphere (p < 0.05, n = 3 in each group; Fig. 1). MNCs significantly reduced the number of neurotrophils and iNOS-positive microglia in the perihematomal area compared with saline-treated animals (P < 0.05, n = 3 in each group; Fig. 2). Moreover, MNCs reduced the expression of high-mobility group protein box-1 (HMGB1), S100β, matrix metalloproteinase 9 (MMP9), and aquaporin 4 (AQP4) in the perihematomal area compared with saline-treated animals (P < 0.05, n = 3 in each group; Fig. 3).
Conclusions: We demonstrate for the first time that intravenously transplanted autologous MNCs can ameliorate brain edema and modulate the inflammatory responses after ICH. This is the first study to perform a bone marrow harvest and autologous infusion of MNCs after ICH. Functional behavioral tests are underway to assess the long-term effects of MNCs as a potential treatment for ICH.
Author Disclosures: S. Suda: None. B. Yang: None. X. Xi: None. K. Schaar: None. K. Parsha: None. J. Aronowski: None. S.I. Savitz: None.
- © 2014 by American Heart Association, Inc.