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Evidence of early vasogenic edema following minor head impact that can be reduced with a vasopressin V1a receptor antagonist.
Kulkarni, Praveen; Bhosle, Mansi R; Lu, Shi-Fang; Simon, Neal S; Iriah, Sade; Brownstein, Michael J; Ferris, Craig F.
Afiliação
  • Kulkarni P; Center for Translational Neuroimaging, Northeastern Univ, Boston, MA, United States.
  • Bhosle MR; Center for Translational Neuroimaging, Northeastern Univ, Boston, MA, United States.
  • Lu SF; Azevan Pharmaceuticals, Bethlehem, PA, United States; Dept.of Biological Sciences, Lehigh University, Bethlehem, PA, United States.
  • Simon NS; Azevan Pharmaceuticals, Bethlehem, PA, United States; Dept.of Biological Sciences, Lehigh University, Bethlehem, PA, United States.
  • Iriah S; Center for Translational Neuroimaging, Northeastern Univ, Boston, MA, United States.
  • Brownstein MJ; Azevan Pharmaceuticals, Bethlehem, PA, United States.
  • Ferris CF; Center for Translational Neuroimaging, Northeastern Univ, Boston, MA, United States; Departments of Psychology and Pharmaceutical Sciences, Northeastern University, Boston, MA, United States. Electronic address: c.ferris@northeastern.edu.
Brain Res Bull ; 165: 218-227, 2020 12.
Article em En | MEDLINE | ID: mdl-33053434
BACKGROUND: Does minor head impact without signs of structural brain damage cause short-term changes in vasogenic edema as measured by an increase apparent diffusion coefficient (ADC) using diffusion weighted imaging? If so, could the increase in vasogenic edema be treated with a vasopressin V1a receptor antagonist? We hypothesized that SRX251, a highly selective V1a antagonist, would reduce vasogenic edema in response to a single minor head impact. METHODS: Lightly anesthetized male rats were subjected to a sham procedure or a single hit to the forehead using a closed skull, momentum exchange model. Animals recovered in five min and were injected with saline vehicle (n = 8) or SRX251 (n = 8) at 15 min post head impact and again 7-8 hrs later. At 2 h, 6 h, and 24 h post injury, rats were anesthetized and scanned for increases in ADC, a neurological measure of vasogenic edema. Sham rats (n = 6) were exposed to anesthesia and scanned at all time points but were not hit or treated. Images were registered to and analyzed using a 3D MRI rat atlas providing site-specific data on 150 different brain areas. These brain areas were parsed into 11 major brain regions. RESULTS: Untreated rats with brain injury showed a significant increase in global brain vasogenic edema as compared to sham and SRX251 treated rats. Edema peaked at 6 h in injured, untreated rats in three brain regions where changes in ADC were observed, but returned to sham levels by 24 h. There were regional variations in the time course of vasogenic edema and drug efficacy. Edema was significantly reduced in cerebellum and thalamus with SRX251 treatment while the basal ganglia did not show a response to treatment. CONCLUSION: A single minor impact to the forehead causes regional increases in vasogenic edema that peak at 6 h but return to baseline within a day in a subset of brain regions. Treatment with a selective V1a receptor antagonist can reduce much of the edema.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Edema Encefálico / Traumatismos Cranianos Fechados / Antagonistas dos Receptores de Hormônios Antidiuréticos Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Edema Encefálico / Traumatismos Cranianos Fechados / Antagonistas dos Receptores de Hormônios Antidiuréticos Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article