Brain-derived neurotrophic factor stimulates production of prostacyclin in cérébral arteries

Anantha Vijay R. Santhanam, Leslie A. Smith, Zvonimir S. Katusic

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background and Purpose-The role of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B, in control of cérébral circulation is poorly understood. The present study was designed to investigate the cérébral 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 μmol/L), PGI2 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 to 10 mol/L) and arachidonic acid (10 to 10 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 mol/L, P<0.05, n=6) and constitutive phospholipase A2 inhibitor, AACOCF3 (2×10 mol/L, P<0.05, n=5). Conclusion-Our results demonstrate that in cérébral 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 cérébral circulation.

Original languageEnglish (US)
Pages (from-to)350-356
Number of pages7
JournalStroke
Volume41
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Basilar arteries
  • Neurotrophins
  • Neurovascular unit
  • Vasodilatation
  • Vasomotor function

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Fingerprint Dive into the research topics of 'Brain-derived neurotrophic factor stimulates production of prostacyclin in cérébral arteries'. Together they form a unique fingerprint.

Cite this