Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup

Laura R. Ment, William B. Stewart, Thomas A. Ardito, Eunice Huang, Joseph A. Madri

Research output: Contribution to journalArticle

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Abstract

Background and Purpose: Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessel s in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems. Methods: We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 nig/kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. Results: Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline- and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p=0.05) and 3 (p=0.0009) and type V collagen staining at postnatal day 2 (p=0.011). Although staining for β1integrins increased across postnatal ages, there were no differences between saline- and indomethacin-treated animals. Conclusions: These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage.

Original languageEnglish (US)
Pages (from-to)1132-1137
Number of pages6
JournalStroke
Volume23
Issue number8
DOIs
StatePublished - Jan 1 1992

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Microvessels
Indomethacin
Laminin
Staining and Labeling
Hemorrhage
Basement Membrane
Collagen Type V
Confocal Microscopy
Formaldehyde
Cell Culture Techniques
Brain
Neoplasms

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup. / Ment, Laura R.; Stewart, William B.; Ardito, Thomas A.; Huang, Eunice; Madri, Joseph A.

In: Stroke, Vol. 23, No. 8, 01.01.1992, p. 1132-1137.

Research output: Contribution to journalArticle

Ment, Laura R. ; Stewart, William B. ; Ardito, Thomas A. ; Huang, Eunice ; Madri, Joseph A. / Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup. In: Stroke. 1992 ; Vol. 23, No. 8. pp. 1132-1137.
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