Next Article in Journal
Anti-Hyperglycemic Effect of Chebulagic Acid from the Fruits of Terminalia chebula Retz
Next Article in Special Issue
Neuroglobin, a Novel Target for Endogenous Neuroprotection against Stroke and Neurodegenerative Disorders
Previous Article in Journal
Optimization of the Extraction of Anthocyanins from the Fruit Skin of Rhodomyrtus tomentosa (Ait.) Hassk and Identification of Anthocyanins in the Extract Using High-Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS)
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2012, 13(5), 6303-6319; doi:10.3390/ijms13056303

Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep

1
Department of Physiology, The University of Auckland, Auckland 1023, New Zealand
2
Department of Ophthalmology, The University of Auckland, Auckland 1023, New Zealand
3
Department of Anatomy, The University of Auckland, Auckland 1023, New Zealand
*
Author to whom correspondence should be addressed.
Received: 9 April 2012 / Revised: 8 May 2012 / Accepted: 14 May 2012 / Published: 22 May 2012
(This article belongs to the Special Issue Neuroprotective Strategies 2012)
View Full-Text   |   Download PDF [763 KB, uploaded 19 June 2014]   |  

Abstract

Hypoxic-ischaemic brain injury at birth is associated with 1–3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 µmol/kg/h for 1 h, followed by 50 µmol/kg/24 h (low dose) or 50 µmol/kg/h for 25 h (high dose) or vehicle only (control group), starting 90 min after the end of ischaemia), following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation). Both peptide infusion groups were associated with a transient significant increase in EEG power between 2–12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling), as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium. View Full-Text
Keywords: fetus; ischaemia; hemichannels; gap junctions; connexins; mimetic peptide fetus; ischaemia; hemichannels; gap junctions; connexins; mimetic peptide
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Davidson, J.O.; Green, C.R.; Nicholson, L.F.B.; Bennet, L.; Gunn, A.J. Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep. Int. J. Mol. Sci. 2012, 13, 6303-6319.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top