Effective Epileptic Treatment Requires Continuous Drug DeliveryContinuous Infusion of SM-216289 Improves Regeneration of Spinal Cord After Injury Tetherless Microdialysis Sampling Enabled by ALZET Pumps T H EA L Z E TO S M O T I C P U M P N E W S L E T T E R - FALL 2 O O 7 Special Delivery ► Neuroscience Focus ALZET Neuroscience Research Since their introduction in 1977, ALZET® Osmotic Pumps have always been incorporated in cutting edge neuroscience research. The ability of ALZET pumps to circumvent the blood-brain barrier (BBB) and enable direct administration of agents to the central nervous system (CNS) opened the door to new and exciting research opportunities. dzef OSMOTIC PUMPS This is evidenced by the pioneering works of Wei etaI. on the study of opioid dependence in rats1, or those of Pettigrew etal. studying neuronal plasticity in cats2. Neuroscientists quickly capitalized on the ability of ALZET pumps to provide precise, continuous dosing, without researcher intervention or animal disturbance, to use them for generating reliable data from behavioral studies, such as those involving feeding, learning, and reproduction. Three decades later, ALZET pumps continue to be an integral component in neuroscience research, as evidenced by the hundreds of publications describing the use of ALZET pumps in studies on spinal cord regeneration, neuropathic pain, stroke & ischemia, neurodegeneration, and more. The new ALZET Special Delivery Newsletter describes select applications of ALZET pumps in neuroscience research, drawn from more than 10,000 published ALZET studies. Please contact us if you would like additional information on any of the applications described here, or if you would like to request references relevant to your research area. 1 Wei etal. Science 1976;193:1262-1263 2Pettigrew et at Nature 1978;271(5647):761-763 P.O. Box 530, Cupertino, CA 95015-9984 phone: 800.692.2990 email: [email protected] www.alzet.com CNS infusion of RNA molecules: a novel treatment for glioblastomas -by Jose Gadea RNA-based therapies hold great promise as potential treatment for many diseases, including glioblastoma multiforme (GBM), a highly malignant and fast growing form of brain cancer for which current therapies are ineffective.1,2 Various experimental approaches are under investigation to evaluate and optimize RNA therapy for GBM. However, a common research challenge is that charged nucleic acids do not readily cross the blood-brain barrier,1’2 Using ALZET Osmotic Pumps to deliver RNA molecules directly to intracranial tumors circumvents this experimental obstacle. Researchers at the University of Illinois, led by Jasti S. Rao, are evaluating GBM therapy based on RNA interference (RNAi), in which small interfering RNA (siRNA) induce messenger RNA degradation, leading to suppression, or "silencing" of target gene expression. Their siRNA-based strategy is aimed at depriving gliomas of their means for tumor growth and invasion by suppressing expression of cathepsins, matrix metalloproteases (MMP) and/or urokinase plasminogen activator receptor (uPAR)M5 In a recent study, Lakka etal. evaluated the efficacy of cytomegalovirus promoter-driven siRNA vectors against uPAR and MMP-9.3 The study showed that direct, intratumoral administration, via ALZET pumps, significantly inhibited glioma tumor growth and invasion in nude mice. Ten days after GBM tumor establishment, ALZET pumps (0.25 pil/'hr) (continued on next page)

NEUROSCIENCE FOCUS (continued from cover) were used to directly administer the siRNA vectors into intracranial tumors via brain cannulae. After 5 weeks, tumor volume was reduced by 40 and 70% in mice treated with siRNAs for MMP-9 and uPAR, respectively, compared to controls. Complete regression of intracranial tumors was achieved in animals treated with siRNA vector for both, uPAR and MMP-9, suggesting that simultaneous blockage of uPAR and MMP-9 genes had a synergistic effect on tumor regression compared to single cell-killing mechanisms, such as apoptosis and production of anti-proliferative...

NEUROSCIENCE FOCUS Effective Epileptic Treatment Requires Continuous Drug Delivery lternate treatments for pharmacoresistant epilepsy are in great demand. Valproic acid (VPA) is a firstline antiepileptic drug that is highly effective. However, its hepatotoxicity limits chronic use. Serralta et al. used ALZET pumps to determine whether continuous intracerebroventricular (ICV) infusion of VPA could avoid systemic toxicity, achieving therapeutic drug concentrations in the brain yet low peripheral organ concentrations. Two VPA administration protocols were tested to assess anticonvulsant efficacy,...

NEUROSCIENCE FOCUS Why Neuroscientists Use ALZET Pumps in Their Research1 “We decided to administer it [creatine] by intracerebroventricular infusion to maximize its bioavailability to the brain.” (p. 187) Lensman et al Brain Research 2006:187-194 “To avoid injection-induced stress and fluctuations of imipramine and the metabolite levels, we administered imipramine using osmotic minipump.” (p. 84) Fujita et al Synapse 2007; 61:78-86 “The use of an osmotic minipump allowed a constant exposure to low doses of CPF-0, simulating continuous environmental exposure. ” Laviola et at. Psychopharmacology...

NEUROSCIENCE FOCUS portable, on-animal system for in vivo sampling of neurotransmitters. Model 2ML1 ALZET pumps (subcutaneous placement) and CMA3 brain cannulae (right striatum) were implanted in a single surgery. The ALZET pump was filled with lactated Ringer's and connected to the inlet port of a CMA/12 microdialysis probe (20,000 Da molecular weight cut-off) using FEP tubing from BAS,4 A BAS tubing connector was used to splice the pump and FEP tubing together, and this connection was safeguarded with both UV-gluing and a generous sheath of tubing protector A small collection vial was attached...

NEUROSCIENCE FOCUS Learn how to use and implant ALZET pumps, or train your staff on these procedures, with the ALZET Surgical Implantation Techniques video available on CD. Request your copy today at www.alzet.com. ALZET Products for Neuroscientists Rat Intrathecal Catheter Short 0007741 Shorter length for non-occipital approach. (Polyurethane (15 cm total length), Includes 10 cm of very fine tubing (OD 0.36 mm); teflon-coated, stainless steel stylet) Neuroscience Publications Therapeutic antibodies, enzyme inhibitors, antidepressants, anticonvulsants, dopaminergics, opioids, neuropeptides, neurotrophic...