Brain-Derived Neurotrophic Factor Stimulates Production of Prostacyclin in Cerebral Arteries

Abstract

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 3Ј,5Ј-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 (37Ϯ5 ng/mL versus 0.006Ϯ0.003 ng/mL, respectively; PϽ0.05; nϭ14). 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 mol/L), PGI 2 production and levels of cyclic adenosine 3Ј,5Ј-monophosphate were significantly elevated only in AdBDNF-treated rabbit basilar arteries (PϽ0.05, nϭ6). Relaxations to acetylcholine (10 Ϫ9 to 10 Ϫ5 mol/L) and arachidonic acid (10 Ϫ9 to 10 Ϫ5 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 Ϫ5 mol/L, PϽ0.05, nϭ6) and constitutive phospholipase A 2 inhibitor, AACOCF3 (2ϫ10 Ϫ5 mol/L, PϽ0.05, nϭ5). Conclusion-Our

Memantine Enhances Recovery From Stroke

“…Given the use-dependent nature of both post-stroke angiogenesis 39 and the neurovascular coupling relationship, it is likely that OIS map plasticity, increased vascular density, and behavioral recovery were mutually dependent processes in MEM-treated animals. Regarding mechanism, BDNF signaling is involved in angiogenesis 40,41 , and BDNF polymorphisms, associated with poor stroke outcome in humans, show reduced angiogenesis in animal models 42 . Our peri-infarct BDNF increases may be relevant in this regard.…”

Brain-derived neurotrophic factor plasma levels and premature cognitive impairment/dementia in type 2 diabetes

“…It has been observed that the concentration of serum BDNF reflects the changes in brain BDNF levels[21-23]; therefore, measuring the concentration of serum BDNF can be used to monitor its changes in the brain[24]. It was recently demonstrated that BDNF stimulates the production of prostacyclin in cerebral arteries[25]; it plays an important role in endothelium-dependent relaxation and has also antiplatelet, vasculoprotective, cardioprotective and anti-atherogenic properties[26-28]. Zoladz et al[29] demonstrated that the decrease in serum BDNF levels after hemodialysis is accompanied by elevated levels of F-isoprostanes and decreased plasma total antioxidant capacity, which might be caused by the increase in oxidative stress induced by hemodialysis.…”

Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like behavior

“…Prostacyclin mediates biological actions through its G-protein-coupled receptor (IP receptor), where it is known to cause vasodilation and anti-platelet aggregation as one of the major vasoprotectors [1, 2] and the endocrine systems [3, 4], and is used as a vascular protective agent and treatment option in pulmonary hypertension [5, 6]. Although PGI 2 is known to be generated in cerebral arteries [7, 8], the consequences of increased PGI 2 secretion within central nervous system (CNS) have not been extensively characterized.…”