PMID- 18374360
OWN - NLM
STAT- MEDLINE
DCOM- 20080924
LR  - 20131121
IS  - 0022-510X (Print)
IS  - 0022-510X (Linking)
VI  - 270
IP  - 1-2
DP  - 2008 Jul 15
TI  - Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in 
      experimental allergic encephalomyelitis.
PG  - 70-6
LID - 10.1016/j.jns.2008.02.011 [doi]
AB  - Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) 
      which includes a neurodegenerative component. Brain derived neurotrophic factor 
      (BDNF) is a neuroprotective agent which might be useful in preventing 
      neurodegeneration but its application has been limited because the blood brain 
      barrier restricts its access to the CNS. We have developed a novel delivery 
      system for BDNF using transformed bone marrow stem cells (BMSC) and undertook 
      studies of EAE to determine whether the delivery of BDNF could reduce 
      inflammation and apoptosis. Mice receiving BDNF producing BMSC had reduced 
      clinical impairment compared to control mice receiving BMSC that did not produce 
      BDNF. Pathological examination of brain and spinal cord showed a reduction in 
      inflammatory infiltrating cells in treated compared to control mice. Apoptosis 
      was reduced in brain and spinal cord based on TUNEL and cleaved Caspase-3 
      staining. Consistent with the known mechanism of action of BDNF on apoptosis, 
      Bcl-2 and Akt were increased in treated mice. Further studies suggested that 
      these increases could be mediated by inhibition of both caspase dependent and 
      caspase independent pathways. These results suggest that the BDNF delivered by 
      the transformed bone marrow stem cells reduced clinical severity, inflammation 
      and apoptosis in this model.
FAU - Makar, Tapas K
AU  - Makar TK
AD  - VA Maryland Healthcare System, Baltimore, MD 21201, USA.
FAU - Trisler, David
AU  - Trisler D
FAU - Sura, Karna T
AU  - Sura KT
FAU - Sultana, Shireen
AU  - Sultana S
FAU - Patel, Niraj
AU  - Patel N
FAU - Bever, Christopher T
AU  - Bever CT
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080418
PL  - Netherlands
TA  - J Neurol Sci
JT  - Journal of the neurological sciences
JID - 0375403
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cystatins)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Myelin Proteolipid Protein)
RN  - 0 (Peptide Fragments)
RN  - 0 (cathestatin B)
RN  - 0 (cystatin, egg-white)
RN  - 0 (myelin proteolipid protein (139-151))
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Brain/drug effects/pathology
MH  - Brain-Derived Neurotrophic Factor/metabolism/*therapeutic use
MH  - Caspase 3/metabolism
MH  - Cell Count
MH  - Cystatins/genetics/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/chemically 
      induced/complications/*drug therapy
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Epoxy Compounds/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - In Situ Nick-End Labeling
MH  - Inflammation/*drug therapy/etiology
MH  - Mice
MH  - Myelin Proteolipid Protein
MH  - Oncogene Protein v-akt/genetics/metabolism
MH  - Peptide Fragments
MH  - Spinal Cord/drug effects/pathology
MH  - Tyrosine/analogs & derivatives/genetics/metabolism
EDAT- 2008/04/01 09:00
MHDA- 2008/09/25 09:00
CRDT- 2008/04/01 09:00
PHST- 2007/09/14 00:00 [received]
PHST- 2008/01/30 00:00 [revised]
PHST- 2008/02/07 00:00 [accepted]
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/09/25 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
AID - S0022-510X(08)00085-3 [pii]
AID - 10.1016/j.jns.2008.02.011 [doi]
PST - ppublish
SO  - J Neurol Sci. 2008 Jul 15;270(1-2):70-6. doi: 10.1016/j.jns.2008.02.011. Epub 
      2008 Apr 18.