PMID- 22407323
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20211021
IS  - 1361-6560 (Electronic)
IS  - 0031-9155 (Print)
IS  - 0031-9155 (Linking)
VI  - 57
IP  - 7
DP  - 2012 Apr 7
TI  - Activation of signaling pathways following localized delivery of systemically 
      administered neurotrophic factors across the blood-brain barrier using focused 
      ultrasound and microbubbles.
PG  - N65-81
LID - 10.1088/0031-9155/57/7/N65 [doi]
AB  - The brain-derived neurotrophic factor (BDNF) has been shown to have broad 
      neuroprotective effects in addition to its therapeutic role in neurodegenerative 
      disease. In this study, the efficacy of delivering exogenous BDNF to the left 
      hippocampus is demonstrated in wild-type mice (n = 7) through the noninvasively 
      disrupted blood-brain barrier (BBB) using focused ultrasound (FUS). The BDNF 
      bioactivity was found to be preserved following delivery as assessed 
      quantitatively by immunohistochemical detection of the pTrkB receptor and 
      activated pAkt, pMAPK, and pCREB in the hippocampal neurons. It was therefore 
      shown for the first time that systemically administered neurotrophic factors can 
      cross the noninvasively disrupted BBB and trigger neuronal downstream signaling 
      effects in a highly localized region in the brain. This is the first time that 
      the administered molecule is tracked through the BBB and localized in the neuron 
      triggering molecular effects. Additional preliminary findings are shown in 
      wild-type mice with two additional neurotrophic factors such as the glia-derived 
      neurotrophic factor (n = 12) and neurturin (n = 2). This further demonstrates the 
      impact of FUS for the early treatment of CNS diseases at the cellular and 
      molecular level and strengthens its premise for FUS-assisted drug delivery and 
      efficacy.
FAU - Baseri, Babak
AU  - Baseri B
AD  - Department of Biomedical Engineering, Columbia University, New York, NY, USA.
FAU - Choi, James J
AU  - Choi JJ
FAU - Deffieux, Thomas
AU  - Deffieux T
FAU - Samiotaki, Gesthimani
AU  - Samiotaki G
FAU - Tung, Yao-Sheng
AU  - Tung YS
FAU - Olumolade, Oluyemi
AU  - Olumolade O
FAU - Small, Scott A
AU  - Small SA
FAU - Morrison, Barclay
AU  - Morrison B
FAU - Konofagou, Elisa E
AU  - Konofagou EE
LA  - eng
GR  - R01 AG038961/AG/NIA NIH HHS/United States
GR  - R01 EB009041/EB/NIBIB NIH HHS/United States
GR  - R01 EB0009041/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120309
PL  - England
TA  - Phys Med Biol
JT  - Physics in medicine and biology
JID - 0401220
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/drug effects/*metabolism
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Delivery Systems/*methods
MH  - Feasibility Studies
MH  - Hippocampus/cytology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Microbubbles
MH  - Nerve Growth Factors/*administration & dosage/metabolism/*pharmacology
MH  - Neurons/cytology/drug effects
MH  - Signal Transduction/*drug effects
MH  - Ultrasonics/*methods
PMC - PMC3919955
MID - NIHMS375337
EDAT- 2012/03/13 06:00
MHDA- 2012/07/17 06:00
PMCR- 2014/02/10
CRDT- 2012/03/13 06:00
PHST- 2012/03/13 06:00 [entrez]
PHST- 2012/03/13 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
PHST- 2014/02/10 00:00 [pmc-release]
AID - 10.1088/0031-9155/57/7/N65 [doi]
PST - ppublish
SO  - Phys Med Biol. 2012 Apr 7;57(7):N65-81. doi: 10.1088/0031-9155/57/7/N65. Epub 
      2012 Mar 9.