Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia

Autor: Francisco Wandosell, Lara Ordoñez, Maria del Carmen Maza, Marta Antón, Maria Jose Perez-Alvarez
Přispěvatelé: UAM. Departamento de Biología
Rok vydání: 2012
Předmět:
Male
Hippocampus
Hippocampal formation
lcsh:RC346-429
Brain Ischemia
Brain ischemia
Random Allocation
0302 clinical medicine
Cortex (anatomy)
Focal ischemia
Cerebral Cortex
0303 health sciences
Estradiol
General Neuroscience
Brain
Biología y Biomedicina / Biología
Immunohistochemistry
Neuroprotection
3. Good health
Stroke
Treatment Outcome
medicine.anatomical_structure
Neurology
Cerebral cortex
MCAO
Neuroglia
Signal Transduction
medicine.medical_specialty
medicine.drug_class
Immunology
Ischemia
Western blot
03 medical and health sciences
Cellular and Molecular Neuroscience
Internal medicine
medicine
Animals
Rats
Wistar
lcsh:Neurology. Diseases of the nervous system
PI3K/AKT/mTOR pathway
030304 developmental biology
business.industry
Research
Akt
medicine.disease
Estrogen
Rats
Disease Models
Animal
Endocrinology
Rat
business
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation
Biblos-e Archivo. Repositorio Institucional de la UAM
instname
Journal of Neuroinflammation, Vol 9, Iss 1, p 157 (2012)
Digital.CSIC. Repositorio Institucional del CSIC
ISSN: 1742-2094
DOI: 10.1186/1742-2094-9-157
Popis: Background Estradiol has been shown to exert neuroprotective effects in several neurodegenerative conditions, including cerebral ischemia. The presence of this hormone prior to ischemia attenuates the damage associated with such events in a rodent model (middle cerebral artery occlusion (MCAO)), although its therapeutic value when administered post-ischemia has not been assessed. Hence, we evaluated the effects of estradiol treatment after permanent MCAO (pMCAO) was induced in rats, studying the PI3K/AKT/GSK3/β-catenin survival pathway and the activation of SAPK-JNK in two brain areas differently affected by pMCAO: the cortex and hippocampus. In addition, we analyzed the effect of estradiol on the glial response to injury. Methods Male rats were subjected to pMCAO and estradiol (0.04 mg/kg) was administered 6, 24, and 48 h after surgery. The animals were sacrificed 6 h after the last treatment, and brain damage was evaluated by immunohistochemical quantification of ‘reactive gliosis’ using antibodies against GFAP and Iba1. In addition, Akt, phospho-AktSer473, phospho-AktThr308, GSK3, phospho-GSK3Ser21/9, β-catenin, SAPK-JNK, and pSAPK-JNKThr183/Tyr185 levels were determined in western blots of the ipsilateral cerebral cortex and hippocampus, and regional differences in neuronal phospho-Akt expression were determined by immunohistochemistry. Results The increases in the percentage of GFAP- (5.25-fold) and Iba1- (1.8-fold) labeled cells in the cortex and hippocampus indicate that pMCAO induced ‘reactive gliosis’. This effect was prevented by post-ischemic estradiol treatment; diminished the number of these cells to those comparable with control animals. pMCAO down-regulated the PI3K/AkT/GSK3/β-catenin survival pathway to different extents in the cortex and hippocampus, the activity of which was restored by estradiol treatment more efficiently in the cerebral cortex (the most affected region) than in the hippocampus. No changes in the phosphorylation of SAPK-JNK were observed 54 h after inducing pMCAO, whereas pMCAO did significantly decrease the phospho-AktSer473 in neurons, an effect that was reversed by estradiol. Conclusion The present study demonstrates that post-pMCAO estradiol treatment attenuates ischemic injury in both neurons and glia, events in which the PI3K/AKT/GSK3/β-catenin pathway is at least partly involved. These findings indicate that estradiol is a potentially useful treatment to enhance recovery after human ischemic stroke.
This work was supported by grants from CIBERNED (an ISCIII initiative), the Spanish Plan Nacional DGCYT, SAF2009-12249-C02-01, EU-FP7-2009-CT222887; by an institutional grants from UAM-Banco Santander (Proyectos de Cooperación Interuniversitaria UAM-Banco Santander con América Latina), and the Fundación Areces.
Databáze: OpenAIRE
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