Corrigendum to: Cerebroprotective properties of SM-20220, a potent Na+/H+ exchange inhibitor, in transient cerebral ischemia in rats [Eur. J. Pharmacol. 353 (1999) 163–168]

Kuribayashi, Yoshikazu; Itoh, Natsuko; Kitano, Masahumi; Ohashi, Naohito

doi:10.1016/s0014-2999(99)00821-3

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“…2,10,18,19) Our previous study showed that SM-20220 prevented the infarction in a rat transient MCA occlusion model 10,11) ; however, the relationship between the timing of drug administration and its beneficial effects was not clear. In the present study, we investigated the dependence of the effect of SM-20220 on infarct size on the dose and on the timing of drug administration.…”

Section: Discussionmentioning

confidence: 99%

“…The surgical procedures were as described previously. 10) Briefly, male Wistar rats (Japan SLC, Hamamatsu, Japan) weighing about 200-240 g were used. All surgical procedures were performed under halothane anesthesia (induction at 4% and maintenance at 1% in 70% N 2 O/30% O 2 ), and core body temperature was maintained at 37°C with a heating pad (BWT-100, Bioresearch Center, Nagoya, Japan) during the surgical procedure.…”

Section: Transient Middle Cerebral Artery (Mca) Occlusionmentioning

confidence: 99%

“…In an early study, SM-20220 attenuated the tissue Na ϩ increase and provided neuroprotection against ischemic injury in the rat. 10) Furthermore, SM-20220 improved the neurological outcome and survival rate in gerbil stroke models. 11) These results suggest that the NHE inhibitor may represent a new class of drugs for the treatment of ischemic brain injury.…”

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confidence: 96%

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Relationship between the Neuroprotective Effect of Na+/H+ Exchanger Inhibitor SM-20220 and the Timing of Its Administration in a Transient Middle Cerebral Artery Occlusion Model of Rats

Horikawa¹,

Kuribayashi²,

Matsui³

et al. 2001

Biological & Pharmaceutical Bulletin

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The aim of this study was to determine the relationship between the neuroprotective effect of SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) and the timing of its administration in an experimental stroke model. Two hours of occlusion followed by 22 h of perfusion of the left middle cerebral artery (MCA) was performed by inserting a nylon thread into the MCA to occlude it, and pulling the thread to initiate reperfusion. Intravenous infusion of SM-20220 for 1 h reduced the infarct volume at doses of 0.2-0.8 mg/kg in a dose-dependent manner without causing changes in the systemic arterial blood pressure or blood gases, when SM-20220 administration was started 1 h after the onset of occlusion. Administration of SM-20220 at a dose of 0.4 mg/kg also reduced the edema formation induced by ischemia. In contrast, SM-20220 failed to reduce the infarction, even at 1.6 mg/kg, when administration was started 2 h after the onset of occlusion. Thus, the therapeutic time window of SM-20220 for this transient MCA occlusion model is 1 h. Daily administration of SM-20220 (0.4 mg/kg) for the 7 d following 1.5 h of middle cerebral artery occlusion reduced the infarct volume with statistical significance ( pϽ0.05), showing that SM-20220 did not merely delay but prevented ischemic damage. Key words Naϩ /H ϩ exchanger; brain ischemia; infarction; SM-20220; edema; therapeutic time window centage of the area of the left hemisphere for each coronal section. The infarct volume was calculated by integration of the infarct areas and the areas of the left hemisphere that were determined for the five coronal sections. Measurement of Arterial Blood Pressure, Gases, and pH In some animals, a femoral artery was cannulated to directly and continuously measure the systemic arterial blood pressure with a pressure transducer (P10EZ, Nihon Kohden, Osaka, Japan) attached to a blood-pressure amplifier (AP-641G, Nihon Kohden) and to sample blood for the analysis of blood gases and pH using I-STAT (Fuso Chemicals, Osaka, Japan). Measurement of Cerebral Water ContentTo measure the brain water content, rats were decapitated 4 h after the onset of reperfusion and the left hemisphere of the occluded MCA territory was cut into 4-mm-thick slices (1 mm anterior-3 mm posterior to the bregma).10) The water content was determined by the dry-weight method. 13)Experimental Protocol The experimental protocol is shown in Fig. 1. SM-20220 was dissolved in 8% polyethylene glycol 400 (w/v) to 0.4 mg/ml and diluted with the same solution to 0.04, 0.08, 0.16, and 0.32 mg/ml. The diluted SM-20220 or just the solution as vehicle was given as an intravenous infusion (5 ml/kg/h) for 1 h using an infusion pump (model 100, KD Scientific, U.S.A.).For the first experiment, the administration of SM-20220 or vehicle was started 1 h after the onset of occlusion, and physiological variables were measured before surgery, before drug administration, and 30 min after the onset of reperfusion; the infarct size was measured 22 h after the onset.For the sec...

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