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Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema.
Hussain, Rashad; Tithof, Jeffrey; Wang, Wei; Cheetham-West, Arokoruba; Song, Wei; Peng, Weiguo; Sigurdsson, Björn; Kim, Daehyun; Sun, Qian; Peng, Sisi; Plá, Virginia; Kelley, Douglas H; Hirase, Hajime; Castorena-Gonzalez, Jorge A; Weikop, Pia; Goldman, Steven A; Davis, Michael J; Nedergaard, Maiken.
Afiliação
  • Hussain R; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA. rashad_hussain@urmc.rochester.edu.
  • Tithof J; Department of Mechanical Engineering, University of Rochester, Rochester, NY, USA.
  • Wang W; Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, USA.
  • Cheetham-West A; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Song W; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Peng W; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Sigurdsson B; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Kim D; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.
  • Sun Q; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.
  • Peng S; Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, USA.
  • Plá V; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Kelley DH; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Hirase H; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Castorena-Gonzalez JA; Department of Mechanical Engineering, University of Rochester, Rochester, NY, USA.
  • Weikop P; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA.
  • Goldman SA; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.
  • Davis MJ; Department of Pharmacology, School of Medicine, Tulane University, New Orleans, LA, USA.
  • Nedergaard M; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.
Nature ; 623(7989): 992-1000, 2023 Nov.
Article em En | MEDLINE | ID: mdl-37968397
Cerebral oedema is associated with morbidity and mortality after traumatic brain injury (TBI)1. Noradrenaline levels are increased after TBI2-4, and the amplitude of the increase in noradrenaline predicts both the extent of injury5 and the likelihood of mortality6. Glymphatic impairment is both a feature of and a contributor to brain injury7,8, but its relationship with the injury-associated surge in noradrenaline is unclear. Here we report that acute post-traumatic oedema results from a suppression of glymphatic and lymphatic fluid flow that occurs in response to excessive systemic release of noradrenaline. This post-TBI adrenergic storm was associated with reduced contractility of cervical lymphatic vessels, consistent with diminished return of glymphatic and lymphatic fluid to the systemic circulation. Accordingly, pan-adrenergic receptor inhibition normalized central venous pressure and partly restored glymphatic and cervical lymphatic flow in a mouse model of TBI, and these actions led to substantially reduced brain oedema and improved functional outcomes. Furthermore, post-traumatic inhibition of adrenergic signalling boosted lymphatic export of cellular debris from the traumatic lesion, substantially reducing secondary inflammation and accumulation of phosphorylated tau. These observations suggest that targeting the noradrenergic control of central glymphatic flow may offer a therapeutic approach for treating acute TBI.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Edema Encefálico / Norepinefrina / Lesões Encefálicas Traumáticas / Sistema Glinfático Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Edema Encefálico / Norepinefrina / Lesões Encefálicas Traumáticas / Sistema Glinfático Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article