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Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces

Qian Li1, Yan Ding2, Paul Krafft2

  • 1Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing, China.

Journal of the American Heart Association
|February 2, 2018
PubMed

Insights

Iron overload in preterm infants contributes to posthemorrhagic hydrocephalus by increasing NCBE expression. Inhibiting NCBE with deferoxamine or siRNA reduces hydrocephalus and improves neurodevelopmental outcomes.

Area of Science:

  • Neonatal neurology
  • Pediatric neurosurgery
  • Cerebrospinal fluid dynamics

Background:

  • Germinal matrix hemorrhage (GMH) is a primary cause of mortality and long-term disability in preterm infants.
  • Posthemorrhagic hydrocephalus (PHH) frequently complicates GMH, impacting infant neurodevelopment.
  • The sodium-coupled bicarbonate exchanger (NCBE) and iron from hemoglobin are implicated in PHH development.

Purpose of the Study:

  • To investigate if iron-responsive proteins (IRPs) regulate NCBE expression.
  • To determine if NCBE influences GMH-induced hydrocephalus.
  • To evaluate if NCBE inhibition can mitigate PHH progression.

Main Methods:

  • A rat pup model of GMH was induced using collagenase or iron trichloride.
  • Deferoxamine (iron chelator) or NCBE-targeting siRNA was administered.
  • NCBE and IRP2 expression, cerebrospinal fluid production, and hydrocephalus severity were assessed.

Main Results:

  • GMH/iron increased NCBE expression and decreased IRP2 expression.
  • Deferoxamine and NCBE inhibition reduced NCBE levels and ameliorated hydrocephalus.
  • Both interventions improved cognitive and motor functions in the treated pups.

Conclusions:

  • Iron-induced NCBE upregulation is a key factor in PHH development.
  • Targeting NCBE offers a potential therapeutic strategy for PHH in preterm infants.
Abstract

Keywords:
braingerminal matrix hemorrhagehemorrhageiron overloadiron‐responsive element‐binding protein 2neonatal ischemiaslc4a10

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