Opposite effects of the gap junction blocker octanol on focal cerebral ischemia occluded for different durations

Abstract

Protectants and executioners have been demonstrated to be used by gap junctions in focal cerebral ischemia. Certain researchers hypothesized that the opposite role of gap junctions may be associated with the injury extent, which has been demonstrated to be highly correlated with occlusion duration. In order to examine this hypothesis directly, the effects of octanol, a frequently used drug, were examined to investigate the role of gap junctions, in rats following middle cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion, respectively. Octanol significantly reduced the infarct volume following 2 h of occlusion concomitant with lower neurological deficits, whereas it enlarged the infarct volume following 30 min of occlusion. Consistently, octanol attenuated the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the hippocampal CA1 region following 2 h of occlusion, while opposite effects were observed for 30 min of occlusion. Further immunohistochemical studies demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein) was downregulated following 2 h of occlusion in the octanol group compared with the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2 protein concomitant with increased Bax protein following 30 min of occlusion. These results indicated that the gap junction blocker octanol can protect against ischemic injury following long-term occlusion, however, can aggravate ischemic injury following short-term occlusion.

Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134

“…Gap26 treatment led to a reduction in both Cx43 expression and activity, therefore reducing the infarct volume and improving the neurological function (9). Gap junction blocker carbenoxolone or octanol played protective roles in ischemic preconditioning or cerebral ischemia (16,17). Recent studies showed that inhibition of Cx43 hemichannels alleviated cerebral ischemia via the toll-like receptor (TLR4) or JAK2/STAT3 pathway (18,19).…”

“…Recent studies showed that inhibition of Cx43 hemichannels alleviated cerebral ischemia via the toll-like receptor (TLR4) or JAK2/STAT3 pathway (18,19). Notably, the intervention of Cx43 or the gap junction occurred immediately after ischemia (during acute phase) in numerous experiments (9,(16)(17)(18)(19). In contrast, few studies investigated their roles in the subacute phase after focal ischemia.…”

In vivo microdialysis with ultra performance liquid chromatography–mass spectrometry for analysis of tetramethylpyrazine and its interaction with borneol in rat brain and blood

“…The total volume was calculated as the following equation: the total volume (%) = S · L , where S is the total infarct area and L is the thickness of slice. Then the infarct volume was assessed as a percentage of the ipsilateral hemispheric volume (%) as described previously (Ding et al, ).…”

Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

“…All the experimental procedures were carried out strictly in compliance with the NIH guidelines for the Care and Use of Laboratory Animals. Focal ischemia was induced by middle cerebral artery occlusion (MCAO) as previously reported (18). Briefly, rats were anesthetized with 350 mg/kg chloral hydrate via intraperitoneal injection.…”

“…Images were captured using an Olympus microscope (Olympus, Tokyo, Japan). To quantify GLT-1, GS and GFAP immunoreactivity (IR), measurement was performed with a computerized image analysis system (Image-Pro-Plus; Media Cybernetics, Silver Spring, MD, USA) according to a previously described method (18). Briefly, a density threshold was first set above the background level to identify the positively stained structure and the area occupied by these structures was measured as the positive area.…”