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Cortical Bilateral Adaptations in Rats Submitted to Focal Cerebral Ischemia: Emphasis on Glial Metabolism.

Authors :
Nonose Y
Gewehr PE
Almeida RF
da Silva JS
Bellaver B
Martins LAM
Zimmer ER
Greggio S
Venturin GT
Da Costa JC
Quincozes-Santos A
Pellerin L
de Souza DO
de Assis AM
Source :
Molecular neurobiology [Mol Neurobiol] 2018 Mar; Vol. 55 (3), pp. 2025-2041. Date of Electronic Publication: 2017 Mar 07.
Publication Year :
2018

Abstract

This study was performed to evaluate the bilateral effects of focal permanent ischemia (FPI) on glial metabolism in the cerebral cortex. Two and 9 days after FPI induction, we analyze [ <superscript>18</superscript> F]FDG metabolism by micro-PET, astrocyte morphology and reactivity by immunohistochemistry, cytokines and trophic factors by ELISA, glutamate transporters by RT-PCR, monocarboxylate transporters (MCTs) by western blot, and substrate uptake and oxidation by ex vivo slices model. The FPI was induced surgically by thermocoagulation of the blood in the pial vessels of the motor and sensorimotor cortices in adult (90 days old) male Wistar rats. Neurochemical analyses were performed separately on both ipsilateral and contralateral cortical hemispheres. In both cortical hemispheres, we observed an increase in tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and glutamate transporter 1 (GLT-1) mRNA levels; lactate oxidation; and glutamate uptake and a decrease in brain-derived neurotrophic factor (BDNF) after 2 days of FPI. Nine days after FPI, we observed an increase in TNF-α levels and a decrease in BDNF, GLT-1, and glutamate aspartate transporter (GLAST) mRNA levels in both hemispheres. Additionally, most of the unilateral alterations were found only in the ipsilateral hemisphere and persisted until 9 days post-FPI. They include diminished in vivo glucose uptake and GLAST expression, followed by increased glial fibrillary acidic protein (GFAP) gray values, astrocyte reactivity, and glutamate oxidation. Astrocytes presented signs of long-lasting reactivity, showing a radial morphology. In the intact hemisphere, there was a decrease in MCT2 levels, which did not persist. Our study shows the bilateralism of glial modifications following FPI, highlighting the role of energy metabolism adaptations on brain recovery post-ischemia.

Details

Language :
English
ISSN :
1559-1182
Volume :
55
Issue :
3
Database :
MEDLINE
Journal :
Molecular neurobiology
Publication Type :
Academic Journal
Accession number :
28271402
Full Text :
https://doi.org/10.1007/s12035-017-0458-x