Abstract
Connexin hemichannels can open during ischemia, resulting in loss of membrane potential, calcium influx, and release of glutamate. In this study, we tested the hypothesis that opening of hemichannels after cerebral ischemia may contribute to delayed evolution of injury. We infused a mimetic peptide that blocks connexin 43 hemichannels into the lateral ventricle of chronically instrumented fetal sheep in utero at 128 ± 1 days gestation (term is 147 days), starting 90 minutes after 30 minutes of severe ischemia induced by reversible bilateral carotid artery occlusion, for either 1 or 25 hours. Sheep were killed 7 days later. Peptide infusion was associated with a graded improvement in recovery of electroencephalographic power after 7 days recovery, from -13 ± 1.9 dB (n = 7) after ischemia-vehicle to -9 ± 1.6 dB (n = 7) after ischemia-short infusion and -5 ± 1.6 dB after ischemia-long infusion (n = 6, p < 0.05). Peptide infusion was associated with reduced seizure activity after ischemia, less frequent status epilepticus (p < 0.05), and earlier return of sleep state cycling (p < 0.05). Ischemia-long infusion (but not ischemia-short infusion) was associated with improved survival of oligodendrocytes in intragyral and periventricular white matter (p < 0.05) and increased brain weight (p < 0.05). Ischemia-long infusion was associated with an intermediate estimate of surviving neurons in the parasagittal cortex of 2.9 ± 0.8 × 10(6), in comparison to sham control (4.3 ± 0.9 × 10(6)) or ischemia-vehicle (1.5 ± 0.4 × 10(6); p < 0.05 vs sham control). These data support the hypothesis that opening of connexin hemichannels is a significant mediator of postischemic white and gray matter dysfunction and injury.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.