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Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke.
- Source :
-
Molecular and cellular endocrinology [Mol Cell Endocrinol] 2018 Sep 05; Vol. 472, pp. 1-9. Date of Electronic Publication: 2018 May 26. - Publication Year :
- 2018
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Abstract
- Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after tMCAO. Apoptotic cell death and expression of natriuretic peptide receptors (NPR-A and NPR-C), K <superscript>+</superscript> channels (K <subscript>ATP</subscript> , K <subscript>V</subscript> and BK <subscript>Ca</subscript> ), and PI3K/Akt and MAPK/ERK1/2 signaling pathways were analyzed. Significant improvement in neurofunctional status, associated to reduction in infarct and edema volumes, was shown in the high-dose ANP group. As to the molecular mechanisms analyzed, high-dose ANP: 1) reduced caspase-3-mediated apoptosis; 2) did not modify the expression of NPR-A and NPR-C, which had been downregulated by the ischemic insult; 3) induced a significant reversion of ischemia-downregulated K <subscript>ATP</subscript> channel expression; and 4) induced a significant reversion of ischemia-upregulated pERK2/ERK2 expression ratio. In conclusion, ANP exerts a significant protective role in terms of both improvement of neurofunctional status and reduction in infarct volume. Modulation of ANP on some molecular mechanisms involved in ischemia-induced apoptotic cell death (K <subscript>ATP</subscript> channels and MAPK/ERK1/2 signaling pathway) could account, at least in part, for its beneficial effect. Therefore, ANP should be considered as a potential adjunctive neuroprotective agent improving stroke outcome after successful reperfusion interventions.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Atrial Natriuretic Factor pharmacology
Brain drug effects
Brain pathology
Brain Ischemia complications
Caspase 3 metabolism
DNA Cleavage drug effects
Down-Regulation
Infarction, Middle Cerebral Artery complications
Infarction, Middle Cerebral Artery pathology
Injections, Intraventricular
MAP Kinase Signaling System drug effects
Male
Neuroprotective Agents pharmacology
Phosphatidylinositol 3-Kinases metabolism
Potassium Channels metabolism
Proto-Oncogene Proteins c-akt metabolism
Rats, Wistar
Receptors, Atrial Natriuretic Factor metabolism
Reperfusion Injury complications
Reperfusion Injury pathology
Stroke complications
Atrial Natriuretic Factor therapeutic use
Brain Ischemia drug therapy
Neuroprotective Agents therapeutic use
Stroke drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8057
- Volume :
- 472
- Database :
- MEDLINE
- Journal :
- Molecular and cellular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 29842904
- Full Text :
- https://doi.org/10.1016/j.mce.2018.05.014