Combined Human Umbilical Cord-Derived Stem Cell and Hyperbaric Oxygen Therapy Effectively Preserved the Neurological Function and Brain Architecture in Rat After Acute Intracerebral Hemorrhage

Abstract

Background: This study tested the hypothesis that combined therapy with human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) and hyperbaric oxygen (HBO) was superior to either one on preserving neurological function and reducing brain-hemorrhagic volume (BHV) in rat after acute intracerebral hemorrhage (ICH) induced by intracranial injection of collagenase. Methods and Results: Adult-male SD rats (n=30) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH + HUCDMSCs/1.2x106 cells/intravenous injection at 3h and days 1/2 after ICH), group 4 (ICH + HBO/at 3h and days 1/2 after ICH) and group 5 (ICH + HUCDMSCs-HBO), and euthanized by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2 to 5 than in group 1 (p<0.001), but it did not differ among groups 2 to 5. By days 7/4/28, the integrity of neurological function was highest in group 1, lowest in group 2 and significantly progressively improved from groups 3 to 5 (all p<0.001). By day 28, the BHV was lowest in group 1, highest in group 2 and significantly lower in group 5 than in groups 3/4 (all p<0.0001). The protein expressions of inflammation (HMGB1/TLR-2/TLR-4/MyD88/TRAF6/p-NF-κB/IFN-γ/IL-1ß/TNF-α), oxidative-stress/autophagy (NOX-1/NOX-2/oxidized protein/ratio of LC3BII/LC3BI) and apoptosis (cleaved-capspase3/PARP), and cellular expressions of inflammation (CD14+, F4/80+) in brain tissues exhibited an identical pattern, whereas cellular levels of angiogenesis (CD31+/vWF+/small-vessel number) and number of neurons (NeuN+) exhibited an opposite pattern of BHV among the groups (all p<0.0001). Conclusion: combined HUCDMSC-HBO therapy offered better outcomes after rat ICH.