Back to Search
Start Over
Oxytocin Reduces Brain Injury and Maintains Blood-Brain Barrier Integrity After Ischemic Stroke in Mice.
- Source :
-
Neuromolecular medicine [Neuromolecular Med] 2020 Dec; Vol. 22 (4), pp. 557-571. Date of Electronic Publication: 2020 Sep 11. - Publication Year :
- 2020
-
Abstract
- The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.
- Subjects :
- Animals
Aquaporin 4 analysis
Aquaporin 4 biosynthesis
Aquaporin 4 genetics
Brain Edema drug therapy
Brain Edema etiology
Brain-Derived Neurotrophic Factor analysis
Cerebral Infarction etiology
Cerebral Infarction pathology
In Situ Nick-End Labeling
Male
Mice
NF-kappa B metabolism
Nerve Tissue Proteins analysis
Nerve Tissue Proteins biosynthesis
Nerve Tissue Proteins genetics
Oxytocin pharmacology
Signal Transduction
Single-Blind Method
Spatial Memory drug effects
Vascular Endothelial Growth Factor A analysis
Blood-Brain Barrier drug effects
Infarction, Middle Cerebral Artery drug therapy
Ischemic Stroke drug therapy
Oxytocin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1174
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuromolecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 32918238
- Full Text :
- https://doi.org/10.1007/s12017-020-08613-3