title: Cortical Bilateral Adaptations in Rats Submitted to Focal Cerebral Ischemia: Emphasis on Glial Metabolism.
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 [18F]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.
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Nonose
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Pedro E
authors.initials: PE
authors.lastname: Gewehr
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Almeida
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Jussemara S
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Bellaver
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Leo A M
authors.initials: LAM
authors.lastname: Martins
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.|Brain Institute of Rio Grande do Sul, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Zimmer
authors.affiliation: Brain Institute of Rio Grande do Sul, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Greggio
authors.affiliation: Brain Institute of Rio Grande do Sul, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Gianina T
authors.initials: GT
authors.lastname: Venturin
authors.affiliation: Brain Institute of Rio Grande do Sul, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Jaderson C
authors.initials: JC
authors.lastname: Da Costa
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.|Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.affiliation: Department of Physiology, University of Lausanne, 1005, Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Pellerin
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.|Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Diogo O
authors.initials: DO
authors.lastname: de Souza
authors.affiliation: Postgraduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 - Anexo Santa Cecília, Porto Alegre, RS, 90035-003, Brazil. adriano.assis@ufrgs.br.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: de Assis
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat
keywords: Astrocytes; Contralateral hemisphere; Energy metabolism; Glial reactivity; Stroke