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Vitamin D improves functional outcomes in neonatal hypoxic ischemic male rats treated with N-acetylcysteine and hypothermia.
Lowe, Danielle W; Fraser, Jamie L; Rollins, Laura Grace; Bentzley, Jessica; Nie, Xingju; Martin, Renee; Singh, Inderjit; Jenkins, Dorothea.
Afiliação
  • Lowe DW; Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States. Electronic address: clarkdw@musc.edu.
  • Fraser JL; Division of Genetics and Metabolism, Children's National Medical Center, Washington, DC, United States. Electronic address: JFraser@cnmc.org.
  • Rollins LG; Department of Psychology, University of Massachusetts, Boston, MA, United States. Electronic address: lgrollins@gmail.com.
  • Bentzley J; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: Jessica.Bentzley@stanford.edu.
  • Nie X; Department of Radiology, Medical University of South Carolina, Charleston, SC, United States. Electronic address: niexi@musc.edu.
  • Martin R; Department of Public Health, Medical University of South Carolina, Charleston, SC, United States. Electronic address: hebertrl@musc.edu.
  • Singh I; Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States. Electronic address: singhi@musc.edu.
  • Jenkins D; Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States. Electronic address: jenkd@musc.edu.
Neuropharmacology ; 123: 186-200, 2017 Sep 01.
Article em En | MEDLINE | ID: mdl-28599922
Hypothermia treatment neuroprotects approximately 50% of neonates who present with moderate to severe hypoxic ischemic encephalopathy (HIE). N-acetylcysteine (NAC), a potent antioxidant, is neuroprotective in combination with hypothermia in neonatal hypoxia-ischemia (HI) female rats, but less protective in males. Vitamin D is a neurosteroid, which may provide immunomodulation and improve outcomes for both sexes. We investigated the efficacy of this combination of drugs with hypothermia after severe HI, as well as potential mechanisms of vitamin D effects in the transition to chronic inflammation. DOL 7 rats were randomized to sham, or HI and hypothermia treated with either saline (HYPO), NAC (50 mg/kg/d, HNAC), or HNAC plus 1,25-dihydroxy-vitamin D3 (0.1 µg/kg/d, HNAC + VitD) daily for 2 weeks. A second set of animals were randomized and treated for 11 days to investigate vitamin D metabolism and inflammatory mediators. Rats treated with HNAC + VitD performed significantly better on tests of strength and use of affected limb, adaptive sensorimotor skills, motor sequence learning, and working memory than either HYPO or HNAC, particularly benefiting male rats. Significantly fewer rats in the HNAC + VitD group had severe hemispheric volume loss. HI injury decreased serum vitamin D at 11 days and induced the enzyme that deactivates vitamin D in the hippocampus, particularly in males. Persistent vitamin D dysregulation was seen in both hippocampi in males, which was not reversed by hypothermia. Vitamin D in combination with hypothermia and NAC supports functional recovery in both sexes of neonatal rats significantly better than hypothermia alone or hypothermia and NAC in this severe HI model.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acetilcisteína / Calcitriol / Fármacos Neuroprotetores / Hipóxia-Isquemia Encefálica / Hipotermia Induzida Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Neuropharmacology Ano de publicação: 2017 Tipo de documento: Article País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acetilcisteína / Calcitriol / Fármacos Neuroprotetores / Hipóxia-Isquemia Encefálica / Hipotermia Induzida Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Neuropharmacology Ano de publicação: 2017 Tipo de documento: Article País de publicação: Reino Unido