SM-20220, a Na+/H+ exchanger inhibitor: effects on ischemic brain damage through edema and neutrophil accumulation in a rat middle cerebral artery occlusion model

Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia

“…It was shown that although SM20220 (0.3 mg/kg) significantly reduced brain edema at 4 h reperfusion after 2 h MCAO in rats, it failed to reduce the infarction (Kuribayashi et al, 1999). However, continuous administration of SM20220 during reperfusion concurrently improved ischemic infarct formation, brain edema, and neutrophil accumulation (Suzuki et al, 2002). The edema formation at 24 h reperfusion in focal ischemia likely represents both cellular and vasogenic edema.…”

The effect of Na+/H+ exchanger-1 inhibition by sabiporide on blood–brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro

“…Cerebral vasogenic edema is a major and potentially fatal complication of acute ischemic stroke (Ayata and Ropper, 2002), and thus, the preservation of the functional and structural integrity of the BBB endothelial cells is likely to be a crucial issue for any therapeutic approach to the amelioration of ischemic brain damage. Several studies have reported that the pharmacological inhibition of Na + /H + exchanger-1 (NHE-1) can attenuate brain damage under various pathologic conditions including ischemia (Luo et al, 2005), and NHE-1 inhibitors have recently been reported to ameliorate brain edema after ischemic insult (Suzuki et al, 2002;Kuribayashi et al, 1999). However, the effects of NHE-1 inhibitors on the disruption of TJ proteins in BBB endothelial cells after cerebral ischemia have not been clarified.…”

Intracellular acidification by inhibition of the Na+/H+-exchanger leads to caspase-independent death of cerebellar granule neurons resembling paraptosis

“…9 Surprisingly, inhibition of the NHE has been reported to protect rats from ischemia-induced brain damage. [10][11][12][13] However, these effects may not be due to the block of the NHE-mediated control of intracellular pH, but due to the block of free fatty acid efflux 14 and block of neutrophil accumulation. 10 To study the role of potassium and acidification in neuronal apoptosis, we investigated the role of the outward delayed rectifier potassium current, changes of pH i and the NHE in apoptosis of cerebellar granule neurons.…”