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

Content Provider	PubMed Central
Author	Davidson, Joanne O. Green, Colin R. Nicholson, Louise F. B. Bennet, Laura Gunn, Alistair J.
Copyright Year	2012
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.
Related Links	http://dx.doi.org/10.3390/ijms13056303
Ending Page	6319
Page Count	17
Starting Page	6303
File Format	PDF
ISSN	14220067
e-ISSN	14220067
Journal	International Journal of Molecular Sciences
Issue Number	5
Volume Number	13
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2012-05-01
Access Restriction	Open
Rights Holder	Molecular Diversity Preservation International (MDPI)
Subject Keyword	Physical and Theoretical Chemistry Inorganic Chemistry Organic Chemistry Spectroscopy Molecular Biology Catalysis Computer Science Applications Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications

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