PMID- 25840805
OWN - NLM
STAT- MEDLINE
DCOM- 20160420
LR  - 20181113
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 35
IP  - 6
DP  - 2015 Aug
TI  - Local Injection of Lenti-BDNF at the Lesion Site Promotes M2 Macrophage 
      Polarization and Inhibits Inflammatory Response After Spinal Cord Injury in Mice.
PG  - 881-90
LID - 10.1007/s10571-015-0182-x [doi]
AB  - There is much evidence to suggest that brain-derived neurotrophic factor (BDNF) 
      is a prominent candidate in promoting neuroprotection, axonal regeneration, and 
      synaptic plasticity following spinal cord injury (SCI). Although some evidence 
      indicates that BDNF has potent anti-oxidative effects and may be involved in the 
      regulation of the immune response, the effects of BDNF in the inflammatory 
      response during the course of secondary damage after SCI is still unclear. The 
      present study was designed to investigate the effects of BDNF with a special 
      focus on their effect on macrophage polarization after SCI. Adult C57 mice 
      underwent T10 spinal cord clip compression injury and received lenti-BDNF vector 
      injections at the epicenter of the lesion site. Four days later, total BDNF 
      levels were greatly increased in animals that received lenti-BDNF injections. 
      Confocal imaging showed that more than 80 % of the lenti-virus infected cells 
      were CD11b-positive macrophages. In addition, the expression of arginase-1 and 
      CD206 (associated with M2 macrophage phenotype) significantly increased in the 
      animals that received lenti-BDNF injections compared with those that received 
      lenti-EGFP injections. On the contrary, the expression of CD16/32 and inducible 
      nitric oxide synthase (M1 phenotype marker) was down-regulated as demonstrated 
      using flow cytometry and immunohistochemistry. Furthermore, the production of 
      interleukin 1beta and tumor necrosis factor alpha was significantly reduced whereas 
      the levels of interleukin 10 and interleukin 13 were elevated in subjects that 
      received lenti-BDNF vector injections. The time course of functional recovery 
      revealed that gradual recovery was observed in the subacute phase in lenti-BDNF 
      group, little improvement was observed in lenti-EGFP group. At the axonal level, 
      significant retraction of the CST axons were observed in lenti-EGFP injected 
      animals relative to lenti-BDNF group by biotinylated dextran amine tracing. In 
      addition, compared to lenti-BDNF group markedly demyelination was observed in the 
      lenti-EGFP group using luxol fast blue staining. In conclusion, we found that 
      BDNF could promote the shift of M1 to M2 phenotype and ameliorate the 
      inflammatory microenvironment. Furthermore, the roles of BDNF in immunity 
      modulation may enhance neuroprotective effects and partially contribute to the 
      locomotor functional recovery after SCI.
FAU - Ji, Xin-Chao
AU  - Ji XC
AD  - Graduate School, The Third Military Medical University, Chongqing, 400038, China, 
      eliteDr@163.com.
FAU - Dang, Yuan-Yuan
AU  - Dang YY
FAU - Gao, Hong-Yan
AU  - Gao HY
FAU - Wang, Zhao-Tao
AU  - Wang ZT
FAU - Gao, Mou
AU  - Gao M
FAU - Yang, Yi
AU  - Yang Y
FAU - Zhang, Hong-Tian
AU  - Zhang HT
FAU - Xu, Ru-Xiang
AU  - Xu RX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150404
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage/*genetics/pharmacology
MH  - Cell Polarity/drug effects
MH  - Female
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors
MH  - Injections, Intralesional
MH  - Injections, Spinal
MH  - Lentivirus/genetics
MH  - Macrophage Activation/drug effects/genetics
MH  - Macrophages/drug effects/metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelitis/genetics/pathology/*prevention & control
MH  - Spinal Cord Injuries/genetics/pathology/*therapy
EDAT- 2015/04/05 06:00
MHDA- 2016/04/21 06:00
CRDT- 2015/04/05 06:00
PHST- 2014/12/16 00:00 [received]
PHST- 2015/03/14 00:00 [accepted]
PHST- 2015/04/05 06:00 [entrez]
PHST- 2015/04/05 06:00 [pubmed]
PHST- 2016/04/21 06:00 [medline]
AID - 10.1007/s10571-015-0182-x [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2015 Aug;35(6):881-90. doi: 10.1007/s10571-015-0182-x. Epub 
      2015 Apr 4.