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Intrathecal administration of Vascular Endothelial Growth Factor (VEGF) elicits phrenic motor facilitation
Author(s) -
DaleNagle Erica Arden,
Mitchell Gordon S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1232.6
Subject(s) - phrenic nerve , tropomyosin receptor kinase b , neurotrophic factors , medicine , vascular endothelial growth factor , brain derived neurotrophic factor , anesthesia , endocrinology , receptor , neuroscience , biology , respiratory system , vegf receptors
VEGF is a hypoxia sensitive growth factor historically viewed as a regulator of angiogenesis. However, recent evidence demonstrates that VEGF is expressed in phrenic motor neurons (Dale et al., FASEB J., 2006), and is neuroprotective for motor neurons (Storkebaum et al. Bioessays , 2004). Brain derived neurotrophic factor (BDNF) elicits phrenic motor facilitation by activating its high affinity receptor TrkB (Baker‐Herman et. al ., 2004). Because VEGF receptors and TrkB are both receptor tyrosine kinases that act via common signaling pathways, we hypothesized that intrathecal VEGF administration would elicit phrenic motor facilitation similar to BDNF. We tested this in anesthetized, pump‐ventilated, vagotomized, and paralyzed, male Sprague‐Dawley rats prepared with intrathecal catheters at C4. Intrathecal VEGF (100ng with 0.1% BSA in artificial aCSF; n=3) increased integrated phrenic motor activity for at least 90 min post‐injection (30 min post‐injection: 63% ± 21% baseline; 60 min post‐injection: 84% ± 9%; 90 min post‐injection: 70% ± 14%; all p < 0.05). Phrenic motor facilitation was not observed in rats treated with intrathecal vehicle control (n=2). VEGF induced phrenic motor facilitation is similar in magnitude and time‐course to BDNF induced facilitation, providing the first evidence that VEGF may be an important factor of plasticity in respiratory motor neurons. Supported by NS057778 and HL80209.