Intrathecal coral-derived cembranolide improves functional recovery after experimental spinal cord i

来源 :第三届国际神经再生高峰论坛暨第五届脊髓损伤治疗与临床试验国际交流会(INRS2013 & 5th ISCITT) | 被引量 : 0次 | 上传用户:gzlwh
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  Functional loss resulting from spinal cord injury (SCI) can often have permanent devastating effects on patient quality of life.The marine-derived natural cembranolide compound WH was originally isolated from the Formosan soft coral.WH significantly decreases the expression of the pro-inflammatory proteins inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in activated microglial cells.Moreover,it attenuates neuronal cytotoxicity and apoptosis.The aim of the present study was to determine whether WH is also a neuroprotective agent that can attenuate the progression of SCI-associated neurodegeneration.WH,methylprednisolone,or saline (control) were administered by intrathecal injection to Wistar rats after a thoracic spinal cord contusion injury was induced using a New York University Multicenter Animal Spinal Cord Injury Study impactor.Compared with methylprednisolone or saline treatment,WH-treated animals showed significantly better locomotor function recovery after SCI.In addition,WH attenuated the SCI-induced upregulation of pro-inflammatory proteins (ICAM-1,iNOS,TNF-alpha,and IL-1beta) and provided neuroprotection by activating the survival signaling proteins Akt,ERK,and CREB.Today,it is possible to produce WH by cultivating soft coral in terrestrial tanks for further assessment in pre-clinical trials.In conclusion,these results show that WH exerts anti-apoptotic effects in the early phase and anti-inflammatory effects in the late phase of SCI.We believe this compound may be a promising therapeutic agent for SCI.
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