Role of gap junctions in early brain injury following subarachnoid hemorrhage.
Gap junction inhibition has been demonstrated to reverse the vascular contraction that follows experimental subarachnoid hemorrhage. This study hypothesizes that the use of established gap junction inhibitors: octonal and carbenoxolone, to interrupt cell to cell communication will provide neuroprotection against early brain injury after SAH. The filament perforation model of SAH was performed in male Sprague-Dawley rats weighing between 300 and 380 g. Octanol (260.46 mg or 781.38 mg/kg), carbenoxolone (100 mg/kg), or vehicles were given via intraperitoneal injection 1 h after SAH. Neurologic deficits and cerebral apoptosis were assessed 24 and 72 h after SAH. In addition, Western blot analysis was performed to confirm the in vivo inhibition of CNS gap junctions. The administration of octanol and carbenoxolone both failed to attenuate the neurological deficits induced by SAH, and they did not reduce neuronal apoptosis. Additionally, carbenoloxone increased post SAH mortality and exacerbated SAH-induced apoptosis. Despite previous studies that show gap junction inhibitors reverse vasospasm following experimental SAH, they failed to improve clinical outcomes or provide neuroprotection in this study.
Ayer
Robert
R
Department of Neurosurgery, Loma Linda University, Loma Linda, CA 92354, USA.
Chen
Wanqiu
W
Sugawara
Takashi
T
Suzuki
Hidenori
H
Zhang
John H
JH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002229:Carbenoxolone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000442:Octanols / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D000442:Octanols; D002229:Carbenoxolone