Peripherally-Derived BDNF Promotes Regeneration of Ascending Sensory Neurons after Spinal Cord Injury 英文参考文献.docVIP

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Peripherally-Derived BDNF Promotes Regeneration of Ascending Sensory Neurons after Spinal Cord Injury 英文参考文献.doc

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Peripherally-Derived BDNF Promotes Regeneration of Ascending Sensory Neurons after Spinal Cord Injury 英文参考文献

Peripherally-DerivedBDNFPromotesRegenerationof AscendingSensoryNeuronsafterSpinalCordInjury Xing-YunSong1.,FangLi1,2.,Feng-HeZhang1,Jin-HuaZhong1,Xin-FuZhou1* 1DepartmentofHumanPhysiologyandCentreforNeuroscience,FlindersUniversity,Adelaide,Australia,2DepartmentofAnatomyandNeurobiology,XiangyaSchoolof Medicine,CentralSouthUniversity,Changsha,People’sRepublicofChina Abstract Background: The blood brain barrier (BBB) and truncated trkB receptor on astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF) applied into the peripheral (PNS) and central nervous system (CNS) thus restrict its application in the treatment of nervous diseases. As BDNF is anterogradely transported by axons, we propose that peripherallyderivedand/orappliedBDNFmayactontheregenerationofcentralaxonsofascendingsensoryneurons. Methodology/PrincipalFindings:Thepresentstudyaimedtotestthehypothesisbyusingconditioninglesionofthesciatic nerveasamodeltoincreasetheexpressionofendogenousBDNFinsensoryneuronsandbyinjectingexogenousBDNFinto theperipheralnerveortissues.HereweshowedthatmostofregeneratingsensoryneuronsexpressedBDNFandp-CREB butnotp75NTR.Conditioning-lesioninducedregenerationofascendingsensoryneuronandtheincreaseinthenumberof p-ErkpositiveandGAP-43positiveneuronswasblockedbytheinjectionoftheBDNFantiserumintheperiphery.Enhanced neurite outgrowth of dorsal root ganglia (DRG) neurons in vitro by conditioning lesion was also inhibited by the neutralizationwiththeBDNFantiserum.ThedeliveryofexogenousBDNFintothesciaticnerveorthefootpadsignificantly increased the number of regenerating DRG neurons and regenerating sensory axons in the injured spinal cord. In a contusioninjurymodel,aninjectionofBDNFintothefootpadpromotedrecoveryofmotorfunctions. Conclusions/Significance:OurdatasuggestthatendogenousBDNFinDRGandspinalcordisrequiredfortheenhanced regenerationofascendingsensoryneuronsafterconditioninglesionofsciaticnerveandperipherallyappliedBDNFmay havetherapeuticeffectsonthespinalcordi