Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation

C. Stryker, D. W. Camperchioli, C. A. Mayer, W. J. Alilain, R. J. Martin, P. M. MacFarlane

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined 1) whether there is a critical postnatal period of ECM expression in brain stem cardiorespiratory control regions and 2) whether the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia [SH (11% O224 h/day)] exposure is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal motor nucleus, cuneate nucleus, and area postrema were immunofluorescently processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key proteoglycan of the ECM and the perineuronal net. From postnatal day (P) 5 (P5), aggrecan and WFA expression increased postnatally in all regions. We observed an abrupt increase in aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, between P10 and P15 followed by a distinct and transient plateau between P15 and P20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (be-tween P10 and P15). SH between P11 and P15 attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, dorsal motor nucleus of the vagus, and area postrema. An intracisternal microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate proteoglycans, rescued the HVR and the increased aggrecan expression. These data indicate that important stages of ECM formation take place in key brain stem respiratory neural control regions and appear to be associated with a heightened vulnerability to hypoxia.

Original languageEnglish
Pages (from-to)R216-R227
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume314
Issue number2
DOIs
StatePublished - Feb 2018

Bibliographical note

Funding Information:
We thank Steve Torontali for construction of the plethysmography chambers and Mia Freer for animal illustration. Present address of W. J. Alilain: Spinal Cord and Brain Injury Research Center, Department of Neuroscience, University of Kentucky, Lexington, KY. GRANTS This work was funded by the Department of Pediatrics, Case Western Reserve University (CWRU), Rainbow Babies & Children’s Hospital. D. Camperchioli was the recipient of a Summer Undergraduate Research Award from the Department of Pediatrics, CWRU.

Funding Information:
This work was funded by the Department of Pediatrics, Case Western Reserve University (CWRU), Rainbow Babies & Children’s Hospital. D. Camperchioli was the recipient of a Summer Undergraduate Research Award from the Department of Pediatrics, CWRU.

Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.

Keywords

  • Brain stem extracellular matrix
  • Breathing
  • Development
  • Hypoxia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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