Role Of MANF Against Secondary Injury Following Traumatic Spinal Cord Injury And Its Mechanism In Rats

PurposeTraumatic spinal cord injury(t-SCI)is a common injury of the central nervous system,usually resulting severe neurological deficits.It has been identified that MANF(mesencephalic astrocyte-derived neurotrophic factor,MANF)plays a neuroprotective role in cerebral ischemia,traumatic cerebral injury and Parkinson's disease.But the neuroprotection of MANF to t-SCI has not yet been investigated.The aim of this study was to investigate the potential effect and its mechanism of MANF in attenuating neuronal apoptosis following t-SCI.MethodsA clip compressive model was used to induce a crush injury of the spinal cord in a total of 150 rats.The spinal cord water content and blood spinal cord barrier(BSCB)permeability were evaluated.The expression levels of MANF and its downstream proteins were examined by western blotting.Immunofluorescence staining of MANF,NeuN,GFAP,Iba-1 and TUNEL staining were also performed.Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites(2 mm rostral and caudal to the epicenter of the injury)per sample.ResultsMANF was mainly expressed in neurons.The expression levels of MANF and its downstream target,pAkt,were gradually increased and after t-SCI.Treatment with MANF increased Bcl-2 and decreased Bax and CC-3 levels;these effects were reversed by treatment with MK2206.The spinal cord water content and BSCB destruction were also ameliorated by MANF treatment.MANF decreases neuronal apoptosis through Akt/MDM-2/p53 pathway after t-SCI.ConclusionThe present research found that MANF has an important role in preventing neuronal apoptosis after t-SCI.The neuroprotective functions of MANF are possibly mediated by Akt/MDM-2/p53 signaling pathway.MANF may,therefore,be a potential therapeutic agent for the treatment of t-SCI.