Parathyroid hormone-related protein induction in focal stroke

A neuroprotective vascular peptide

Janet L Funk, Elton Migliati, Guanjie Chen, Hongbing Wei, Jonathan Wilson, Katherine J. Downey, Paul J. Mullarky, Bruce M Coull, Paul F. McDonagh, Leslie S Ritter

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Parathyroid hormone-related protein (PTHrP) is a multifunctional peptide that enhances blood flow in non-central nervous system (CNS) vascular beds by causing vasodilation. PTHrP expression is induced in non-CNS organs in response to ischemia. Experiments were therefore undertaken to determine whether PTHrP can be induced in brain in response to ischemic injury and whether PTHrP can act locally as a vasodilator in the cerebral vasculature, an effect that could be neuroprotective in the setting of stroke. PTHrP expression was examined by Northern analysis and immunohistochemical staining in male Sprague-Dawley rats subjected to permanent middle cerebral artery occlusion (MCAO). Vasodilatory effects of superfused PTHrP(1-34) on pial arterioles were determined by intravital fluorescence microscopy. Effects of PTHrP(1-34) peptide administration on MCAO infarction size reduction were assessed. PTHrP expression was induced in the ischemic hemisphere as early as 4 h after MCAO and remained elevated for up to 24 h. Increased immunoreactive PTHrP at sites of ischemic tissue injury was located in the cerebral microvessels. Superfusion with PTHrP(1-34) peptide for up to 25 min increased pial arteriolar diameter by 30% in normal animals. In animals with permanent MCAO, PTHrP(1-34) peptide treatment significantly decreased cortical infarct size (-47%). In summary, PTHrP expression increases at sites of ischemic brain injury in the cerebrovasculature. This local increase in PTHrP could be an adaptive response that enhances blood flow to the ischemic brain, thus limiting cell injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume284
Issue number4 53-4
StatePublished - Apr 1 2003

Fingerprint

Parathyroid Hormone-Related Protein
Blood Vessels
Stroke
Middle Cerebral Artery Infarction
Peptides
Nervous System
Wounds and Injuries
Brain
Arterioles
Microvessels
Vasodilator Agents
Fluorescence Microscopy
Vasodilation
Brain Injuries
Sprague Dawley Rats
Ischemia
Staining and Labeling

Keywords

  • Brain
  • Cerebrovasculature
  • Infarction
  • Vasodilation

ASJC Scopus subject areas

  • Physiology

Cite this

Parathyroid hormone-related protein induction in focal stroke : A neuroprotective vascular peptide. / Funk, Janet L; Migliati, Elton; Chen, Guanjie; Wei, Hongbing; Wilson, Jonathan; Downey, Katherine J.; Mullarky, Paul J.; Coull, Bruce M; McDonagh, Paul F.; Ritter, Leslie S.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 284, No. 4 53-4, 01.04.2003.

Research output: Contribution to journalArticle

Funk, Janet L ; Migliati, Elton ; Chen, Guanjie ; Wei, Hongbing ; Wilson, Jonathan ; Downey, Katherine J. ; Mullarky, Paul J. ; Coull, Bruce M ; McDonagh, Paul F. ; Ritter, Leslie S. / Parathyroid hormone-related protein induction in focal stroke : A neuroprotective vascular peptide. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2003 ; Vol. 284, No. 4 53-4.
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AU - Chen, Guanjie

AU - Wei, Hongbing

AU - Wilson, Jonathan

AU - Downey, Katherine J.

AU - Mullarky, Paul J.

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