Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and function as ligandmodulated transcription factors that regulate gene expression in many important biological processes. The PPAR␦ subtype has the highest expression in the brain and is postulated to play a major role in neuronal cell function; however, the precise physiological roles of this receptor remain to be elucidated. Herein, we show that the high-affinity PPAR␦ agonists L-165041 [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid] and GW501516 [2-methyl4-((4 -methyl-2-(4-trifluoromethylphenyl) -1,3 -triazol-5-yl)-methylsulfanyl)phenoxy acetic acid] protect against cytotoxininduced SH-SY5Y cell injury in vitro and both ischemic brain injury and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in vivo. In the SH-SY5Y studies, treatment with L-165041 or GW501516 significantly and concentrationdependently attenuated cell death following thapsigargin, 1-methyl-4-phenylpyridinium, or staurosporine exposure, with the extent of damage correlated with the level of caspase-3 inhibition. In the transient (90 min) middle cerebral artery occlusion model of ischemic brain injury in rats, i.c.v. infusion of L-165041 or GW501516 significantly attenuated the ischemic brain damage measured 24 h after reperfusion. Moreover, the PPAR␦ agonists also significantly attenuated MPTP-induced depletion of striatal dopamine and related metabolite contents in mouse brain. These results demonstrate that subtypeselective PPAR␦ agonists possess antiapoptotic properties in vitro, which may underlie their potential neuroprotective potential in in vivo experimental models of cerebral ischemia and Parkinson's disease (PD). These findings suggest that PPAR␦ agonists could be useful tools for understanding the role of PPAR␦ in other neurodegenerative disorders, as well as attractive therapeutic candidates for stroke and neurodegenerative diseases such as PD.

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To quantitatively and noninvasively evaluate common carotid atherosclerosis in a series of patients, we measured the stiffness parameter p, which represents the mechanical properties of the vessel. /3 was calculated from the relationship between blood pressure and the diameter of the artery as measured by an ultrasonic, phase-locked, echotracking system. Increases in the severity grade of atherosclerosis as subsequently determined at autopsy were correlated with increased Rvalues in 60 common carotid arteries (r=.68).C ommon carotid atherosclerosis has been reported to precede cerebral atherosclerosis.1 -2 Therefore, evaluating the severity of sclerosis in the common carotid artery may prove to be a useful prognosticator for the development of cerebrovascular sclerosis in asymptomatic individuals. Early detection of this condition can help to reduce the risk of cerebrovascular accident. Atherosclerosis causes structural changes in artery walls that alter their physical properties. The stiffness parameter /3 proposed by Hayashi et al 3 is one quantitative index of the elastic properties of large arteries. /3 can be calculated from the measurements of blood pressure and arterial diameter. Although advances in ultrasound technique have made it possible to visualize common carotid arteries, their quantitative measurement has only recently been developed. Nakayama and Sato 4 have designed an ultrasonic measuring method of arterial wall movement that uses a phase-tracking system. Moreover, Yoshimura et al 5 have developed an ultrasonic Doppler flow meter with this system that allows transcutaneous measurement of the arterial diameter and its pulsatile change. We calculated f3 from the measurements of blood pressure, arterial diameter, and its pulsatile change. A few clinical studies have included measurements of /3, 67 but no previous study has compared clinical studies with pathological findings.The aim of this study was to define the relationship between fi of the common carotid artery and the severity grade of atherosclerosis on the basis of postmortem pathological analysis. These findings may serve as reference data for noninvasively diagnosing atherosclerosis.Received August 17,1993; revision accepted December 9,1993. From the Departments of Preventive Medicine (T.W.) and Internal Medicine IV (K.K., K.F., K.I., E.T., T.F., T.U., and S.Y.), The Jikei University School of Medicine, Tokyo, Japan.Correspondence to Takashi Wada, MD, Department of Preventive Medicine, The Jikei University School of Medicine, 25-8 Nishi-shinbashi 3-chome, Minato-ku, Tokyo 105, Japan.Patients with f) values greater than 13 had a pathological diagnosis of atherosclerosis in the common carotid artery. The sensitivity of this discrimination ratio was 80%, and the specificity was 80% as well. Thus, /3 shows promise as a useful diagnostic indicator for detecting asymptomatic common carotid atherosclerosis. (Arteriosder Thromb. 1994;14:479-482 MethodsHayashi et al 3 analyzed the behavior of arterial walls by assessing changes in vess...

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