Delayed Treatment With an Adenosine Kinase Inhibitor, GP683, Attenuates Infarct Size in Rats With Temporary Middle Cerebral Artery Occlusion

Abstract

Background and Purpose-Brain ischemia is associated with a marked increase in extracellular adenosine levels. This results in activation of cell surface adenosine receptors and some degree of neuroprotection. Adenosine kinase is a key enzyme controlling adenosine metabolism. Inhibition of this enzyme enhances the levels of endogenous brain adenosine already elevated as a result of the ischemic episode. We studied a novel adenosine kinase inhibitor (AKI), GP683, in a rat focal ischemia model. Methods-Four groups of 10 adult Sprague-Dawley rats were exposed to 90 minutes of temporary middle cerebral artery (MCA) occlusion. Animals were injected intraperitoneally with vehicle, 0.5 mg/kg, 1.0 mg/kg, or 2.0 mg/kg of GP683 30, 150, and 270 minutes after the induction of ischemia by a researcher blinded to treatment group. The animals were euthanatized 24 hours after MCA occlusion, and brains were stained with 2,3,5-triphenyltetrazolium chloride. We measured brain temperatures in a separate group of 6 rats before and after administration of 1.0 mg/kg GP683. Results-All treated groups showed a reduction in infarct volumes, but a significant effect was observed only in the 1.0 mg/kg-dose group (44% reduction, Pϭ0.0077). Body weight, physiological parameters, neurological scores, and mortality did not differ among the 4 groups. No apparent behavioral side effects were observed. Brain temperatures did not change after drug injection. Conclusions-Our

Neuroanesthesia and Intensive Care Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists

“…37 Many other image analysis softwares are used for measuring the infarct areas in different experiments. 3,12,14 In our experiment, two hours of MCAO in control animals resulted in the infarct volume of 217.3 ± 79.5 mm 3 (corrected infarct volume), which is similar with the infarct volume of 210.39 ± 31.25 mm 3 (corrected infarct volume) after two hours of MCAO in another report. 36 The isoflurane-induced rapid tolerance to cerebral ischemia might be used to manage patients undergoing surgical procedures in which cerebral ischemia may occur.…”

“…35 The ischemic model used in our experiments is widely accepted. 3,9,12,36 In the present study, the infarct areas were measured by using Adobe Photoshop, the method was also used for measuring the infarct areas in the heart. 37 Many other image analysis softwares are used for measuring the infarct areas in different experiments.…”

“…The difference between the areas of the right and the left hemisphere in a slice was considered to be edema and subtracted from the infarct area of that slice (corrected infarct volume = uncorrected infarct volume -[right hemisphere's volume -left hemisphere's volume]). 12 The result was multiplied by slice thickness and all six slices were summated to find the total corrected infarct volume.…”

Effect of Jiaji electroacupuncture in transected rat spinal cord

“…Studies have shown that acupuncture preconditioning can exert favorable protective effects on hypoxia and ischemia in the heart, brain, gastrointestinal tract, and spinal cord, and it has been suggested that preconditioning induces a protective effect via generation of a trigger factor [31]. Our present results showed a greater effect in the Jiaji electroacupuncture preconditioning group than in the postinjury electroacupuncture treatment group.…”

Delayed Treatment with MLN519 Reduces Infarction and Associated Neurologic Deficit Caused by Focal Ischemic Brain Injury in Rats via Antiinflammatory Mechanisms Involving Nuclear Factor-κB Activation, Gliosis, and Leukocyte Infiltration

“…Reperfusion has been shown to enhance injury due to production of reactive oxygen species and increased edema (Kuroiwa et al, 1988;Lipton and Rosenberg, 1994) but also allows for restoration of metabolic activity to the compromised areas (Hallenbeck and Dutka, 1990;Halsey et al, 1991). Critically, this model is well established and been shown to be highly sensitive to pharmacological intervention with neuroprotective drugs as a means to reduce the resulting brain infarction (Britton et al, 1997;Clemens and Panetta, 1994;Kawasaki-Yatsugi et al, 1998;Tatlisumak et al, 1998;Tortella et al, 1999;. Previous studies with MLN519 have reported neuroprotection in this same model of MCAO with a dose of 0.1 mg/kg delivered 4 hours after MCAO , as well as in combination with tissue plasminogen activator in a model of embolic stroke in rats (Zhang et al, 2001).…”