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Alleviation of Cerebral Infarction of Rats With Middle Cerebral Artery Occlusion by Inhibition of Aquaporin 4 in the Supraoptic Nucleus
- Source :
- ASN NEURO, ASN Neuro, Vol 12 (2020)
- Publication Year :
- 2020
- Publisher :
- SAGE Publications, 2020.
-
Abstract
- In ischemic stroke, vasopressin hypersecretion is a critical factor of cerebral swelling and brain injury. To clarify neural mechanisms underlying ischemic stroke-evoked vasopressin hypersecretion, we observed the effect of unilateral permanent middle cerebral artery occlusion (MCAO) in rats on astrocytic plasticity and vasopressin neuronal activity in the supraoptic nucleus (SON) as well as their associated cerebral injuries. MCAO for 8 hr caused cerebral infarction in the MCAO side where water contents also increased. Immunohistochemical examination revealed that the percentage of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2)-positive vasopressin neurons in the SON of MCAO side was significantly higher than that in non-MCAO side and in sham group. In the cortex, pERK1/2 and aquaporin 4 expressions increased significantly in the infarction area, while glial fibrillary acidic protein (GFAP) reduced significantly compared with the noninfarction side in brain cortex. Microinjection of N-(1,3,4-Thiadiazolyl)nicotinamide-020 [TGN-020, a specific blocker of aquaporin 4] into the SON blocked MCAO-evoked increases in pERK1/2 in the SON as well as the reduction of GFAP and the increase in pERK1/2 and aquaporin 4 in the infarction area of the cortex. Finally, oxygen and glucose deprivation reduced GFAP expression and the colocalization and molecular association of GFAP with aquaporin 4 in the SON in brain slices. These effects were blocked by TGN-020 and/or phloretin, a blocker of astrocytic volume-regulated anion channels. These findings indicate that blocking aquaporin 4 in the SON may reduce the activation of vasopressin neurons and brain injuries elicited by vasopressin during ischemic stroke.
- Subjects :
- 0301 basic medicine
Male
Niacinamide
Vasopressin
Pathology
medicine.medical_specialty
Microinjections
vasopressin
MAP Kinase Signaling System
Supraoptic nucleus
lcsh:RC321-571
03 medical and health sciences
0302 clinical medicine
Thiadiazoles
ischemic stroke
Medicine
Animals
Middle cerebral artery occlusion
cardiovascular diseases
Rats, Wistar
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Aquaporin 4
Original Paper
Glial fibrillary acidic protein
biology
business.industry
Cerebral infarction
Brain edema
General Neuroscience
astrocytes
Infarction, Middle Cerebral Artery
medicine.disease
Rats
030104 developmental biology
nervous system
glial fibrillary acidic protein
Ischemic stroke
biology.protein
Neurology (clinical)
business
Supraoptic Nucleus
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 17590914
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- ASN NEURO
- Accession number :
- edsair.doi.dedup.....947468095d014e0affbd1715dc806905