Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model

Autor: Juan Antonio González-Barrios, Daniel Limon, Bertha Alicia León-Chávez, Alejandro Gonzalez-Vazquez, José-Luis Garate-Morales, Jorge Cebada, Ana Karina Aguilar-Peralta, Guadalupe Garcia-Robles, Maricela Torres-Soto, Victor Manuel Blanco-Alvarez, Guadalupe Soto-Rodriguez, Daniel Martinez-Fong, Eduardo Brambila, Constantino Tomas-Sanchez, Luis-Angel Aguilar-Carrasco
Jazyk: angličtina
Rok vydání: 2016
Předmět:
lcsh:Immunologic diseases. Allergy
0301 basic medicine
Male
Chemokine
Programmed cell death
Article Subject
Neuroimmunomodulation
Immunology
Morris water navigation task
chemistry.chemical_element
Zinc
Pharmacology
Neuroprotection
Hippocampus
Drug Administration Schedule
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Chlorides
Memory
Immunology and Allergy
Medicine
Animals
Rats
Wistar
Receptor
Maze Learning
Neuroinflammation
Nitrites
Neurons
biology
business.industry
Nitrotyrosine
General Medicine
Rats
Disease Models
Animal
030104 developmental biology
Neuroprotective Agents
chemistry
Zinc Compounds
Hypoxia-Ischemia
Brain
biology.protein
Fibroblast Growth Factor 2
Receptors
Chemokine
Chemokines
lcsh:RC581-607
business
030217 neurology & neurosurgery
Research Article
Zdroj: Journal of Immunology Research
Journal of Immunology Research, Vol 2016 (2016)
ISSN: 2314-7156
2314-8861
Popis: Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.
Databáze: OpenAIRE
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