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Perinatal Azithromycin Provides Limited Neuroprotection in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy.
Mike, Jana Krystofova; White, Yasmine; Hutchings, Rachel S; Vento, Christian; Ha, Janica; Manzoor, Hadiya; Lee, Donald; Losser, Courtney; Arellano, Kimberly; Vanhatalo, Oona; Seifert, Elena; Gunewardena, Anya; Wen, Bo; Wang, Lu; Wang, Aijun; Goudy, Brian D; Vali, Payam; Lakshminrusimha, Satyan; Gobburu, Jogarao V S; Long-Boyle, Janel; Wu, Yvonne W; Fineman, Jeffrey R; Ferriero, Donna M; Maltepe, Emin.
Afiliação
  • Mike JK; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • White Y; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Hutchings RS; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Vento C; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Ha J; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Manzoor H; Department of Biomedical Engineering (H.M., A.W.), University of California Davis.
  • Lee D; School of Pharmacy, University of Maryland, Baltimore (D.L., J.V.S.G.).
  • Losser C; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Arellano K; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Vanhatalo O; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Seifert E; Department of Pediatrics (B.D.G., P.V., B.D.G., P.V., S.L., J.-L.B., O.V.), University of California Davis.
  • Gunewardena A; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Wen B; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Wang L; College of Pharmacy, University of Michigan, Ann Arbor (B.W., L.W.).
  • Wang A; College of Pharmacy, University of Michigan, Ann Arbor (B.W., L.W.).
  • Goudy BD; Department of Biomedical Engineering (H.M., A.W.), University of California Davis.
  • Vali P; Department of Biomedical Engineering (H.M., A.W.), University of California Davis.
  • Lakshminrusimha S; Department of Pediatrics (B.D.G., P.V., B.D.G., P.V., S.L., J.-L.B., O.V.), University of California Davis.
  • Gobburu JVS; Department of Pediatrics (B.D.G., P.V., B.D.G., P.V., S.L., J.-L.B., O.V.), University of California Davis.
  • Long-Boyle J; Department of Pediatrics (B.D.G., P.V., B.D.G., P.V., S.L., J.-L.B., O.V.), University of California Davis.
  • Wu YW; School of Pharmacy, University of Maryland, Baltimore (D.L., J.V.S.G.).
  • Fineman JR; Initiative for Pediatric Drug and Device Development, San Francisco, CA (J.V.S.G., J.R.F., E.M.).
  • Ferriero DM; Department of Pediatrics (J.K.M., Y.W., R.S.H., C.V., J.H., C.L., K.A., O.V., E.S., A.G., J.L.-B., Y.W.W., J.R.F., D.M.F., E.M.), University of California San Francisco.
  • Maltepe E; School of Pharmacy (J.L.-B.), University of California San Francisco.
Stroke ; 54(11): 2864-2874, 2023 11.
Article em En | MEDLINE | ID: mdl-37846563
ABSTRACT

BACKGROUND:

Hypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal azithromycin administration in near-term lambs following global ischemic injury to support earlier treatment approaches.

METHODS:

Ewes and their lambs of both sexes (n=34, 141-143 days) were randomly assigned to receive azithromycin or placebo before delivery as well as postnatally. Lambs were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Outcomes were assessed over a 6-day period.

RESULTS:

While maternal azithromycin exhibited relatively low placental transfer, azithromycin-treated lambs recovered spontaneous circulation faster following the initiation of cardiopulmonary resuscitation and were extubated sooner. Additionally, peri- and postnatal azithromycin administration was well tolerated, demonstrating a 77-hour plasma elimination half-life, as well as significant accumulation in the brain and other tissues. Azithromycin administration resulted in a systemic immunomodulatory effect, demonstrated by reductions in proinflammatory IL-6 (interleukin-6) levels. Treated lambs exhibited a trend toward improved neurodevelopmental outcomes while histological analysis revealed that azithromycin supported white matter preservation and attenuated inflammation in the cingulate and parasagittal cortex.

CONCLUSIONS:

Perinatal azithromycin administration enhances neonatal resuscitation, attenuates neuroinflammation, and supports limited improvement of select histological outcomes in an ovine model of hypoxic-ischemic brain injury/encephalopathy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Lesões Encefálicas / Hipóxia-Isquemia Encefálica / Hipotermia Induzida Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Lesões Encefálicas / Hipóxia-Isquemia Encefálica / Hipotermia Induzida Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2023 Tipo de documento: Article