title: Neuroprotection and Blood-Brain Barrier Restoration by Salubrinal After a Cortical Stab Injury.
abstract: Following a central nervous system (CNS) injury, restoration of the blood-brain barrier (BBB) integrity is essential for recovering homeostasis. When this process is delayed or impeded, blood substances and cells enter the CNS parenchyma, initiating an additional inflammatory process that extends the initial injury and causes so-called secondary neuronal loss. Astrocytes and profibrotic mesenchymal cells react to the injury and migrate to the lesion site, creating a new glia limitans that restores the BBB. This process is beneficial for the resolution of the inflammation, neuronal survival, and the initiation of the healing process. Salubrinal is a small molecule with neuroprotective properties in different animal models of stroke and trauma to the CNS. Here, we show that salubrinal increased neuronal survival in the neighbourhood of a cerebral cortex stab injury. Moreover, salubrinal reduced cortical blood leakage into the parenchyma of injured animals compared with injured controls. Adjacent to the site of injury, salubrinal induced immunoreactivity for platelet-derived growth factor subunit B (PDGF-B), a specific mitogenic factor for mesenchymal cells. This effect might be responsible for the increased immunoreactivity for fibronectin and the decreased activation of microglia and macrophages in injured mice treated with salubrinal, compared with injured controls. The immunoreactivity for PDGF-B colocalized with neuronal nuclei (NeuN), suggesting that cortical neurons in the proximity of the injury were the main source of PDGF-B. Our results suggest that after an injury, neurons play an important role in both, the healing process and the restoration of the BBB integrity. J. Cell. Physiol. 232: 1501-1510, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal (CSIC), Madrid, Spain.|Unidad de Neurología Experimental, Hospital Nacional de Parapléjicos (SESCAM), Madrid, Spain.
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Barreda-Manso
authors.affiliation: Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal (CSIC), Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Yanguas-Casás
authors.affiliation: Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal (CSIC), Madrid, Spain.|Unidad de Neurología Experimental, Hospital Nacional de Parapléjicos (SESCAM), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Nieto-Sampedro
authors.affiliation: Unidad de Neurología Experimental, Hospital Nacional de Parapléjicos (SESCAM), Madrid, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Romero-Ramírez
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000293:injuries* / Q000473:pathology; D002934:Cinnamates / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005070:Evans Blue / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014951:Wounds, Stab / Q000188:drug therapy* / Q000473:pathology
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D002934:Cinnamates; D005353:Fibronectins; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C496827:salubrinal; D005070:Evans Blue; D013890:Thiourea