Blocked angiogenesis in Galectin-3 null mice does not alter cellular and behavioral recovery after middle cerebral artery occlusion stroke

Autor: Nicola J. Lewis, Alastair M. Buchan, Christopher C. Young, Keith J. Brooks, Micaela M Jenkins, Francis G. Szele, Françoise Poirier, Osama Al-Dalahmah
Přispěvatelé: Department of Physiology, Anatomy and Genetics, University of Oxford, University of Oxford [Oxford], Nuffield Department of Clinical Medicine [Oxford], Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health RO1 NS-42253, MRC UK and Foundation Leducq, Rhodes Scholarship
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Vascular Endothelial Growth Factor A
Time Factors
Angiogenesis
Galectin 3
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Subependymal zon
Cerebral Ventricles
Mice
chemistry.chemical_compound
0302 clinical medicine
Ischemia
Gliosis
Stroke
Migration
Mice
Knockout
0303 health sciences
Neovascularization
Pathologic
Mental Disorders
Neurogenesis
Brain
Infarction
Middle Cerebral Artery
Vascular endothelial growth factor
medicine.anatomical_structure
Neurology
Galectin-3
Cerebral cortex
Cerebrovascular Circulation
Neural repair
Brain Infarction
medicine.medical_specialty
Doublecortin Protein
Subventricular zone
Neuroprotection
lcsh:RC321-571
03 medical and health sciences
Internal medicine
medicine
Animals
cardiovascular diseases
Middle cerebral artery occlusion
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
030304 developmental biology
business.industry
Recovery of Function
medicine.disease
Disease Models
Animal
Endocrinology
Gene Expression Regulation
chemistry
nervous system
Angiogenesis Inducing Agents
business
Neuroscience
030217 neurology & neurosurgery
Zdroj: Neurobiology of Disease
Neurobiology of Disease, Elsevier, 2014, 63, pp.155-64. ⟨10.1016/j.nbd.2013.11.003⟩
Neurobiology of Disease, Vol 63, Iss, Pp 155-164 (2014)
ISSN: 1095-953X
0969-9961
DOI: 10.1016/j.nbd.2013.11.003⟩
Popis: International audience; Angiogenesis is thought to decrease stroke size and improve behavioral outcomes and therefore several clinical trials are seeking to augment it. Galectin-3 (Gal-3) expression increases after middle cerebral artery occlusion (MCAO) and has been proposed to limit damage 3days after stroke. We carried out mild MCAO that damages the striatum but spares the cerebral cortex and SVZ. Gal-3 gene deletion prevented vascular endothelial growth factor (VEGF) upregulation after MCAO. This inhibited post-MCAO increases in endothelial proliferation and angiogenesis in the striatum allowing us to uniquely address the function of angiogenesis in this model of stroke. Apoptosis and infarct size were unchanged in Gal-3(-/-) mice 7 and 14days after MCAO, suggesting that angiogenesis does not affect lesion size. Microglial and astrocyte activation/proliferation after MCAO was similar in wild type and Gal-3(-/-) mice. In addition, openfield activity, motor hemiparesis, proprioception, reflex, tremors and grooming behaviors were essentially identical between WT and Gal-3(-/-) mice at 1, 3, 7, 10 and 14days after MCAO, suggesting that penumbral angiogenesis has limited impact on behavioral recovery. In addition to angiogenesis, increased adult subventricular zone (SVZ) neurogenesis is thought to provide neuroprotection after stroke in animal models. SVZ neurogenesis and migration to lesion were overall unaffected by the loss of Gal-3, suggesting no compensation for the lack of angiogenesis in Gal-3(-/-) mice. Because angiogenesis and neurogenesis are usually coordinately regulated, identifying their individual effects on stroke has hitherto been difficult. These results show that Gal-3 is necessary for angiogenesis in stroke in a VEGF-dependant manner, but suggest that angiogenesis may be dispensable for post-stroke endogenous repair, therefore drawing into question the clinical utility of augmenting angiogenesis.
Databáze: OpenAIRE
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