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Combination of mild therapeutic hypothermia and adipose-derived stem cells for ischemic brain injury

neural regeneration Research 2018年第10期13卷 1759-1770页

作者： Kai Zhao Rui Li Sheng Bi Yu Li Long Liu Yu-Long Jia Peng Han Chang-Cong Gu Xi-Ze Guo Wan-Ping Zhang Chun Wang Chun-Ying Pei Lin-Lu Tian Li-Xian Li Department of Neurosurgery First Affiliated Hospital of Harbin Medical University Department of Neurology University of Pennsylvania Department of Neurology First Affiliated Hospital of Harbin Medical University Department of Immunology Harbin Medical University

Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia（33°C） was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL） staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the m RNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approac

关键词： nerve regeneration brain injury stroke rats transient middle cerebrum artery occlusion cerebral resuscitation mild therapeutic hypothermia adipose-derived stem cells combination therapy neuroprotection neuronal cell death neural regeneration

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