$388 Thursday, November 10, 2005 Poster Abstracts

80% (wt/wt) magnetite). Given the high redrculat ion times of t-PA- loaded magnetic spheres in the human circulation, these results are promising and support the concept of magnetically guided, non- invasive, targeted t-PA delivery.

1128 Magnetically guided targeted drug delivery across the blood brain barrier: a mathematical feasibility gtudy

Chen, H 1.~, Kanfinski, MD 2~, Caviness, TL 1,~, Guy, SG ~, Rosengart, A J 1.. 1Departments of Neurology and Surgery" (Neurosurgery), The University of Chicago and Pritzker School of Medicine, Chicago, USA; 2Chemical Engineering Division, Argonne National Laboratory, Argonne, USA; 3Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, USA; 14Collaborative Investigators for Applied Nanotechnology in Medicine * Co-Principal Investigators

We propose a magnetically guided delivery system utilizing designer, biocompatible, and non-toxic superparamagnetic nanoparticles for drug delivery across the blood brain barrier. Different from traditional magnetic drug targeting system, the new approach exploits the use of tfigh gradient magnetic separation (HGMS) within the brain paren- chyma. A small biocompatible, ferromagnetic mesh is implanted into at brain targeting site. An externally applied magnetic field (homo- geneous or gradient) magnetizes the implanted mesh inducing local magnetic distortions and creating relatively high magnetic gradients. Such magnetic gradients can redirect freely circulating medicated magnetic spheres leading to focal concentration of the entrapped drug(s) selectively at the target site. We now present the first feasibility evaluation of such a delivery system and investigated the collection efficiency (CE) of magnetic nanoparricles from capillary flow by studying 1) an implanted ferromagnetic micro-wire mesh (distant to capillaries) plus external magnetic field gradients (homogenous and gradient), and 2) extracranial maguets only, no mesh. The results show that the presence of a ferromagnetic mesh improves CE of nanoparticles into the parenchyma. At the presence of one piece of micro-wire, 25?,'8 and 40?,'8 CE is achieved at 0.5 and 1.0 mm/s local flow velocities, respectively. Envisioning multiple implanted mesh wires the proposed system shows promise for future magnetic drug targeting across the blood brain barrier.

1129 The prevalence of ealdftcation in lntracranial Arteries and its risk factors

Xiang Yan Chen, MD l#, Ka Sing Wong, MD 2, Wynuie W.M. Lain, MD 3, Ho Keung Ng, MD ~. 1Department ofAnawmical & Cellular Pathology, the Chinese University of Hong Kong, Shatin, Hong Kong SAR; 2Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Shatin, Hong Kong SAR; 3Department of Diagnostic Radiology & Organ Imaging, the Chinese University of Hong Kong, Shatin, Hong Kong SAR

Purpose: To investigate the prevalence and location of calcification in intracranial arteries and its risk factors. Methods: All patients referred to PWH for brain CT screening in Dec 2004 were recruited. All patients received a questionnaire regarding their medical history and serum chemistry values. CT examina- tions were done with a 16- slice MDCT (multi-detector-row computed tomography). Results: Four hundred and ninety cases, (mean age, 62.92 years old), were included. There were three hundred and forty cases (69.4%) had intracranial artery caldficarion. The highest prevalence of intracranial artery caldficarion was seen in ICA (60%), followed by in vertebral artery (20%), in MCA (5%) and basilar artery (15%). The cases with calcification were significantly older than those without calcification (p < 0.001). A significantly higher prevalence of calcification were seen among the cases with versus without hypertension (p < 0.001),

diabetes (p < 0.001), renal failure (p < 0.05), atrial fibrillation (iJ < 0.05), smoking (p < 0.05), hyperlipidemia (iJ < 0.001), ischemic heart disease (p < 0.05) and ischemic stroke (p < 0.001). The mean value of serum phosphate, serum urea and CRP level was also significantly lfigher in the cases with intracranial artery calcification (p < 0.05, respectively). Stepwise nmltiple logistic regression (shown in table 3) showed age (RR -- 2.795 per 10 years), a history of ischemic stroke (RR -- 3.915), and white blood cells count (RR -- 1.107) to be independently associated with intracranial artery calcification. Contusions: Vascular calcification occurs frequently in the intracranial arteries. Besides age, lfistory of ischemic stroke and WBC may be also risk factors of intracranial artery calcification.

1130 Atorvastatin protects against Cerebral Infarction via Inhibiting N A D P H Oxidase-Derived Superoxide in Isehemie Stroke

Hong, H Lz, Zeng, JS z, Guan, y y 3 Chen, AF 1. 1Departments of Pharmacology and Neurology and Neuroseienee Program, Michigan State University, East Lansing, USA; 2Department of Neurology, Sun Yat-Sen University, Guangzhou, China; 3Department of Pharmacology, Sun Yat-Sen University, Guangzhou, China

Background: Statins have recently been shown to exert neuronal protection in ischemic stroke. Reactive oxygen species, specifically superoxide formed during the early phase of reperfusion, augment neuronal injury. N A D P H oxidase is a key enzyme for superoxide production. The present study tested the hypothesis that atorvastarin protects against cerebral infarction via inhibition of N A D P H oxidase- derived superoxide in transient focal ischemia. Methods: Transient focal ischemia was created in halothane- anesthetized adult male Sprague-Dawley rats (1250-300 g) by middle cerebral artery occlusion (MCAO). Atorvastarin (Lipitor TM, 10 mg/kg) was administrated subcutaneously 3 times before MCAO. Infarct volume was measured by triphenyltetrazolium chloride staining. N A D P H oxidase enzymatic activity and superoxide levels were quart- rifled in both the ischemic core and penmnbral regions by hidgenin (15 #M)-enhanced chemiluminescence. The expression of NADPH oxidase membrane subunit gp91 ph°~' and membrane-translocated subunit p47 pl~°~ and small GTPase Roe-1 were determined by Western blot analyses. Results: N A D P H oxidase activity and superoxide levels increased following reperfusion and peaked within 2 hours of reperfusion in the penumbra, but not in the ischemic core in MCAO rats. Ator- vastatin pretreatment prevented this increases, blunted the expression of membrane subunit gp91 pl,°~ and prevented the translocation of cytoplasmic subunit p47 pl~°~ to the membrane in the penmnbra 2 hours after reperfusion. Consequently, cerebral infarct volume was signifi- cantly reduced in atorvastatin-treated compared to non-treated MCAO rats 24 hours after reperfusion. Conclusion: These results indicate that atorvastatin protects against cerebral infarction via inhibition of N A D P H oxidase-derived super- oxide in transient focal ischenfia.

1131 Itdiibition of Brain GTP Cydohydrolase I and Telrahydrobiopterin Attenuates Cerebral Infarction via Reducing iNOS and Peroxynitrite in Ischemic Stroke

Zheng, JS 1, Hong, H 1, Majid, A ~, Kaufinan, DI ~, Chen, AF t. :Departments of Pharmacology and Neurology and Neuroscience Program, 3fiehigan State University, East Lansing, USA

Background: Inducible nitric oxide synthase (iNOS)-derived peroxyni- trite (ONOO-) during ischemia/reperfusion contributes to ischemic brain injury. However, iNOS regulation in ischemic stroke remains unknown. Tetrahydrobiopterin (BH4) is an essential cofactor for NOS activity. The present study tested the hypothesis that inhibition of endogenous BH4 rate-limiting etazyme GTP cyclohydrolase I