Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport.

Autor:	Bahari F; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA., Dzhala V; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA., Balena T; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA., Lillis KP; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA., Staley KJ; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 Sep 03; Vol. 147 (9), pp. 3216-3233.
DOI:	10.1093/brain/awae161
Abstrakt:	Intraventricular haemorrhage is a common complication of premature birth. Survivors are often left with cerebral palsy, intellectual disability and/or hydrocephalus. Animal models suggest that brain tissue shrinkage, with subsequent vascular stretch and tear, is an important step in the pathophysiology, but the cause of this shrinkage is unknown. Clinical risk factors for intraventricular haemorrhage are biomarkers of hypoxic-ischaemic stress, which causes mature neurons to swell. However, immature neuronal volume might shift in the opposite direction in these conditions. This is because immature neurons express the chloride, salt and water transporter NKCC1, which subserves regulatory volume increases in non-neural cells, whereas mature neurons express KCC2, which subserves regulatory volume decreases. When hypoxic-ischaemic conditions reduce active ion transport and increase the cytoplasmic membrane permeability, the effects of these transporters are diminished. Consequentially, mature neurons swell (cytotoxic oedema), whereas immature neurons might shrink. After hypoxic-ischaemic stress, in vivo and in vitro multi-photon imaging of perinatal transgenic mice demonstrated shrinkage of viable immature neurons, bulk tissue shrinkage and blood vessel displacement. Neuronal shrinkage was correlated with age-dependent membrane salt and water transporter expression using immunohistochemistry. Shrinkage of immature neurons was prevented by prior genetic or pharmacological inhibition of NKCC1 transport. These findings open new avenues of investigation for the detection of acute brain injury by neuroimaging, in addition to prevention of neuronal shrinkage and the ensuing intraventricular haemorrhage, in premature infants. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu