Online citations, reference lists, and bibliographies.
← Back to Search

Discovery Of Adrenomedullin In Rat Ischemic Cortex And Evidence For Its Role In Exacerbating Focal Brain Ischemic Damage.

X Wang, T. Yue, F. Barone, R. White, R. K. Clark, R. Willette, A. Sulpizio, N. Aiyar, R. Ruffolo, G. Feuerstein
Published 1995 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Focal brain ischemia is the most common event leading to stroke in humans. To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post-MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies localized AM to ischemic neuronal processes, and radioligand (125I-labeled CGRP) displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP receptors in brain cortex. The cerebrovascular function of AM was studied using synthetic AM microinjected onto rat pial vessels using a cranial window or applied to canine basilar arteries in vitro. AM, applied abluminally, produced dose-dependent relaxation of preconstricted pial vessels (P < 0.05). Intracerebroventricular (but not systemic) AM administration at a high dose (8 nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic cortical neurons, the demonstration of the direct vasodilating effects of the peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain damage suggests that AM plays a significant role in focal ischemic brain injury.
This paper references



This paper is referenced by
Adrenomedulin from a Pheochromocytoma to the Eye : Implications of the Adrenomedulin Research for Endocrinology in the 21 st Century
K. Takahashi (2003)
10.1016/j.ajpath.2013.02.015
Adrenomedullin-RAMP2 system is crucially involved in retinal angiogenesis.
Yasuhiro Iesato (2013)
10.1038/nrn1408
HIF1 and oxygen sensing in the brain
F. Sharp (2004)
10.1007/978-3-7091-6346-7_87
Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in children: a preliminary report.
C. Robertson (2000)
10.2492/INFLAMMREGEN.28.105
The anti-inflammatory and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain
K. Miyashita (2008)
10.1139/Y97-074
Use of differential display reverse transcription--polymerase chain reaction for discovery of induced adrenomedullin gene expression in focal stroke.
G. Feuerstein (1997)
10.1006/BBRC.1998.8110
Transcriptional regulation of human adrenomedullin gene in vascular endothelial cells.
T. Ishimitsu (1998)
10.1097/CCM.0b013e3181e8ac1a
Impaired cerebral blood flow autoregulation during posttraumatic arterial hypotension after fluid percussion brain injury is prevented by phenylephrine in female but exacerbated in male piglets by extracellular signal-related kinase mitogen-activated protein kinase upregulation
W. Armstead (2010)
10.1006/JSRE.1999.5634
Reduction in vascular responsiveness to adrenomedullin during sepsis.
P. Wang (1999)
10.1016/S0167-0115(03)00028-4
Adrenomedullin in perinatal medicine
R. Iorio (2003)
10.1385/1-59259-836-6:253
Technologies of disease-related gene discovery using preclinical models of stroke.
X. Wang (2005)
10.1016/S0002-9440(10)62555-2
Neutralization of adrenomedullin inhibits the growth of human glioblastoma cell lines in vitro and suppresses tumor xenograft growth in vivo.
L. Ouafik (2002)
10.1016/j.neuroscience.2010.09.021
Lack of adrenomedullin, but not complement factor H, results in larger infarct size and more extensive brain damage in a focal ischemia model
O. Hurtado (2010)
10.1006/DBIO.1998.9073
Expression of adrenomedullin, a hypotensive peptide, in the trophoblast giant cells at the embryo implantation site in mouse.
S. Yotsumoto (1998)
10.5772/38545
The Molecules: Abnormal Vasculatures in the Splanchnic and Systemic Circulation in Portal Hypertension"
Y. Iwakiri (2012)
10.1002/CPHY.CP070210
Amylin and Related Proteins: Physiology and Pathophysiology
G. J. Cooper (2011)
10.1620/TJEM.193.79
Adrenomedullin from a pheochromocytoma to the eye: implications of the adrenomedullin research for endocrinology in the 21st century.
K. Takahashi (2001)
10.1074/JBC.M006512200
Coordinated Up-regulation by hypoxia of adrenomedullin and one of its putative receptors (RDC-1) in cells of the rat blood-brain barrier.
A. Ladoux (2000)
10.1097/00004647-199911000-00012
Functional Calcitonin Gene-Related Peptide Type 1 and Adrenomedullin Receptors in Human Trigeminal Ganglia, Brain Vessels, and Cerebromicrovascular or Astroglial Cells in Culture
M. Moreno (1999)
10.1002/JEMT.10059
Adrenomedullin functions as an important tumor survival factor in human carcinogenesis
F. Cuttitta (2002)
10.1097/00001756-200112210-00055
Adrenomedullin regulates blood–brain barrier functions in vitro
B. Kis (2001)
10.1016/j.peptides.2019.170133
Polyethylene glycol-conjugated human adrenomedullin as a possible treatment for vascular dementia
S. Nagata (2019)
10.1089/HUM.2004.15.1243
Adrenomedullin gene delivery protects against cerebral ischemic injury by promoting astrocyte migration and survival.
Chun-fang Xia (2004)
10.1046/j.1365-2826.2002.00778.x
Cerebral Endothelial Cells are a Major Source of Adrenomedullin
B. Kis (2002)
10.1016/S0169-328X(00)00148-0
Adrenomedullin receptors in rat cerebral microvessels.
H. Kobayashi (2000)
10.1038/srep33495
Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage
L. Ochoa-Callejero (2016)
10.1291/HYPRES.26.S61
Adrenomedullin, an autocrine mediator of blood-brain barrier function.
B. Kis (2003)
The identification of novel tumour-specific transcripts in pancreatic carcinoma using differential display
Angela Bhatia (1997)
10.1016/j.canlet.2008.06.019
Hypoxia-inducible adrenomedullin accelerates hepatocellular carcinoma cell growth.
S. C. Park (2008)
10.1080/14767050903181468
New markers of neonatal neurology
D. Gazzolo (2009)
10.3892/mmr.2016.5001
Temporal profiles of blood pressure, circulating nitric oxide, and adrenomedullin as predictors of clinical outcome in acute ischemic stroke patients
M. Serrano-Ponz (2016)
10.1161/01.CIR.101.4.415
Induction of a myocardial adrenomedullin signaling system during ischemic heart failure in rats.
E. Oie (2000)
See more
Semantic Scholar Logo Some data provided by SemanticScholar