PMID- 20019327
OWN - NLM
STAT- MEDLINE
DCOM- 20100223
LR  - 20220331
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 41
IP  - 2
DP  - 2010 Feb
TI  - Brain-derived neurotrophic factor stimulates production of prostacyclin in 
      cerebral arteries.
PG  - 350-6
LID - 10.1161/STROKEAHA.109.564492 [doi]
AB  - BACKGROUND AND PURPOSE: The role of brain-derived neurotrophic factor (BDNF) and 
      its receptor, tropomyosin receptor kinase B, in control of cerebral circulation 
      is poorly understood. The present study was designed to investigate the cerebral 
      vascular effects of BDNF in vivo. METHODS: Replication incompetent adenovirus 
      encoding either rat BDNF (AdBDNF) or green fluorescent protein was injected 
      intracisternally into rabbits. Forty-eight hours later, animals were euthanized. 
      Plasma and cerebrospinal fluid levels of BDNF were measured by enzyme-linked 
      immunosorbent assay, vasomotor function of isolated basilar arteries was studied 
      in organ chambers, protein expression in the basilar arteries was studied by 
      Western blotting, prostanoid levels were measured by enzyme-linked immunosorbent 
      assay, and cyclic adenosine 3',5'-monophosphate levels were measured by 
      radioimmunoassay. RESULTS: The levels of BDNF in the cerebrospinal fluid were 
      significantly elevated in AdBDNF-treated rabbits as compared with adenovirus 
      encoding green fluorescent protein-treated rabbits (37+/-5 ng/mL versus 
      0.006+/-0.003 ng/mL, respectively; P<0.05; n=14). Western blotting studies 
      revealed that in basilar arteries, AdBDNF increased protein expression of 
      prostacyclin synthase, whereas expression of endothelial nitric oxide synthase 
      and phosphorylated (Ser 1177) endothelial nitric oxide synthase remained 
      unchanged. During incubation with arachidonic acid (1 micromol/L), PGI(2) 
      production and levels of cyclic adenosine 3',5'-monophosphate were significantly 
      elevated only in AdBDNF-treated rabbit basilar arteries (P<0.05, n=6). 
      Relaxations to acetylcholine (10(-9) to 10(-5) mol/L) and arachidonic acid 
      (10(-9) to 10(-5) mol/L) were significantly potentiated in basilar arteries from 
      rabbits injected with AdBDNF. Potentiation of relaxations to acetylcholine in 
      AdBDNF-treated basilar arteries was inhibited by the nonselective cyclooxygenase 
      inhibitor, indomethacin (10(-5) mol/L, P<0.05, n=6) and constitutive 
      phospholipase A(2) inhibitor, AACOCF3 (2x10(-5) mol/L, P<0.05, n=5). CONCLUSIONS: 
      Our results demonstrate that in cerebral arteries, BDNF-induced activation of 
      tropomyosin receptor kinase B receptor signaling in vivo promotes prostacyclin 
      biosynthesis. These findings provide novel mechanistic insight into the vascular 
      protective effect of BDNF in cerebral circulation.
FAU - Santhanam, Anantha Vijay R
AU  - Santhanam AV
AD  - Departments of Anesthesiology, and Molecular Pharmacology and Experimental 
      Therapeutics, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.
FAU - Smith, Leslie A
AU  - Smith LA
FAU - Katusic, Zvonimir S
AU  - Katusic ZS
LA  - eng
GR  - R01 HL091867-01A2/HL/NHLBI NIH HHS/United States
GR  - R01 HL053524/HL/NHLBI NIH HHS/United States
GR  - HL-91867/HL/NHLBI NIH HHS/United States
GR  - HL-53524/HL/NHLBI NIH HHS/United States
GR  - R01 HL091867/HL/NHLBI NIH HHS/United States
GR  - R01 HL053524-13/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091217
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cerebrospinal Fluid Proteins)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.99.4 (prostacyclin synthetase)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Arachidonic Acid/pharmacology
MH  - Basilar Artery/metabolism
MH  - Brain Ischemia/metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/blood/*cerebrospinal fluid/genetics
MH  - Cerebral Arteries/*metabolism
MH  - Cerebrospinal Fluid Proteins/analysis/metabolism
MH  - Cerebrovascular Circulation/*physiology
MH  - Cyclic AMP/metabolism
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Disease Models, Animal
MH  - Epoprostenol/*biosynthesis
MH  - Genetic Vectors
MH  - Intramolecular Oxidoreductases/metabolism
MH  - Male
MH  - Muscle, Smooth, Vascular/metabolism
MH  - Rabbits
MH  - Receptor, trkB/*metabolism
MH  - Transfection
MH  - Up-Regulation/genetics
MH  - Vasodilation/*physiology
PMC - PMC2811757
MID - NIHMS167009
EDAT- 2009/12/19 06:00
MHDA- 2010/02/24 06:00
PMCR- 2011/02/01
CRDT- 2009/12/19 06:00
PHST- 2009/12/19 06:00 [entrez]
PHST- 2009/12/19 06:00 [pubmed]
PHST- 2010/02/24 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - STROKEAHA.109.564492 [pii]
AID - 10.1161/STROKEAHA.109.564492 [doi]
PST - ppublish
SO  - Stroke. 2010 Feb;41(2):350-6. doi: 10.1161/STROKEAHA.109.564492. Epub 2009 Dec 
      17.