Background and Purpose
Stroke is one of major cause of death all over the world. Recently, local fibrinolytic treatment of brain embolism with t-PA is effective during a few hours after the onset with the infarction tissue alive. Although the threshold of cerebral blood flow (CBF) for tissue viability which closely related to treatment efficiency is reported to be 35 % in comparison with the normal CBF value, the parameters related to oxygen metabolism can directly define the pathological condition of the lesion in vivo. Furthermore, experiments using small animal models are valuable to explore pathological alterations of the lesion and estimate novel therapeutic methods. A permanent ischemia rat model is usually applied for this purpose although the alteration of oxygen metabolism after the onset is not clear. We have previously reported a new imaging tool, injectable O-15-oxygen, to estimate oxygen metabolism in a small animals. On these bases, alteration of oxygen metabolism after the onset of brain infarction was evaluated using injectablec-15-oxyge cO-15-oxygen to characterize the MCA occlusion rat model in this paper.
Methods
Male Sprague-Dawley rats (250 to 310 g) were used for this study. The right middle cerebral artery (MCA) was occluded intraluminally using a nylon monofilament under the anesthesia. Rats were divided into two groups; 1 h or 24 hours after the operation, two serial PET scans (SHR-7700L, Hamamatsu Photonics, Hamamatsu, Japan) were performed using O-15-water (for estimation of CBF) and radiolabelled O-15-oxygen blood (injectable -15-oxygen1 O-15-oxygen) 1 . Each PET scan consisted of 12 × 10 second with arterial blood sampling. Each parameter was calculated on each hemisphere of successive four slices.
Results
At 1 h in the right hemisphere, CBF decrease (ratio of right to left hemisphere: 0. 65 ± 0.17) and compensatory increase of oxygen extraction fraction (OEF) (1.17 ± 0.22) were observed, leading to light decrease of cerebral metabolic rate for oxygen (CMRO2) (0.74 ± 0.15). At 24 hours, marked CBF decrease (0.53 ± 0.17) and loss of compensatory OEF mechanism resulted in serious decrease of CMRO2 (0.48 ± 0.17).
Conclusion
Compensatory mechanism of oxygen metabolism was observed 1 h after the onset of MCA occlusion while lost at 24 hours. It meant the progression of the pathological condition during 24 hours and these changes in small animals could be detected using injectablec-15-oxyge cO-15-oxygen and PET. Therefore, injectable O-15-oxygen can be used for the evaluation of new therapeutic methods to improve the brain infarction in the functional point of view.