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Umbilical cord-derived MSC and hyperbaric oxygen therapy effectively protected the brain in rat after acute intracerebral haemorrhage |
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| Authors: | Hon-Kan Yip Kun-Chen Lin Pei-Hsun Sung John Y. Chiang Tsung-Cheng Yin Re-Wen Wu Kuan-Hung Chen |
| Affiliation: | 1. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;2. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Contribution: Investigation (lead), Methodology (equal);3. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Contribution: Methodology (equal);4. Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan Contribution: Writing - review & editing (equal);5. Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Contribution: Methodology (equal);6. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan |
| Abstract: | 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 haemorrhagic volume (BHV) in rat after acute intracerebral haemorrhage (ICH) induced by intracranial injection of collagenase. Adult male SD rats (n = 30) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH +HUCDMSCs/1.2 × 106 cells/intravenous injection at 3h and days 1 and 2 after ICH), group 4 (ICH +HBO/at 3 hours and days 1 and 2 after ICH) and group 5 (ICH +HUCDMSCs-HBO), and killed by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2-5 than in group 1 (P < .001), but it did not differ among groups 2 to 5. By days 7, 14 and 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 < .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 < .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 LC3B-II/LC3B-I) 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 < .0001). These results indicate that combined HUCDMSC-HBO therapy offered better outcomes after rat ICH. |
| Keywords: | hyperbaric oxygen intracerebral haemorrhage mesenchymal stem cells neurological function |