References on the use of ALZET® Osmotic Pumps to Study Neurodegenerative Diseases

1. Alzheimer's Disease

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2. Amyotrophic Lateral Sclerosis

Q0041 Dugan,L.L., Turetsky,M., Cheng,D., Lobner,D., Wheeler,M., Robert Almli,C, Shen,C.K.F., Luh,T.Y., Choi,D.W., Lin,T.S., . Carboxyfullerenes as neuroprotective agents. Proc.Natl.Acad.Sci. 1997; 94(--):9434-9439. >>> Carboxyfullerene, C3; Saline, physiological; IP; Mice (transgenic); 2004; 2 months; Controls received mp w/ vehicle; long-term study; neurodegenerative (amyotrophic lateral sclerosis); animal info (G93A SOD1 G1, 10 weeks old); functionality of mp verified by residual volume; pumps replaced after 4 weeks; behavioral testing (motor performance).

P9501 Smith,R.A. Antisense oligonucleotide therapy for neurodegenerative disease. Journal of Clinical Investigation 2006; 116(-8-):2290-2296. >>> Oligonucleotide, phosphorothioate antisense; oligonucleotide, phosphorothioate missense; Saline; CSF/CNS; Rat; Rat (transgenic); 14, 28 days; Controls received mp w/ missene oligo; antisense (SOD1); brain tissue distribution; animal info (Sprague Dawley, SOD1G93A Tg, 65-75 days old); neurodegenerative (ALS).

P9435 Pitzer,C., Krueger,C., Plaas,C., Kirsch,F., Dittgen,T., Mueller,R., Laage,R., Kastner,S., Suess,S., Spoelgen,R., Henriques,A., Ehrenreich,H., Schaebitz,W.R., Bach,A., Schneider,A. Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis. Brain 2008; 131(--):3335-3347. >>> Colony-stimulating factor, G; Sorbitol; sodium acetate buffer; tween 80; SC; Mice (transgenic); 2004; 4, 8 weeks; 4 days; Controls received mp w/ vehicle; functionality of mp verified by G-CSF serum concentration; replacement therapy (sciatic nerve axotomy); long-term study; pumps replaced after 4 weeks; half-life (p. 5) 4 hours in humans and rodents; brain tissue distribution; peptide; animal info (female, C57BL/6, wt, SOD1(G93A)Tg, 11 wks old); neurodegenerative (ALS); behavioral testing (rotarod test, motor performance); 0.004% Tween 80 used.

P9379 Gowing,G., Philips,T., Van Wijmeersch,B., Audet,J.N., Dewil,M., Van den Bosch,L., Billiau,A.D., Robberecht,W., Julien,J.P. Ablation of Proliferating Microglia Does Not Affect Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase. Journal of Neuroscience 2008; 28(-41-):10234-10244. >>> Ganciclovir; CSF/CNS (intrathecal); Mice (transgenic); 2004; 30 days; Controls received mp w/ saline; animal info (CD11b-Tkmt-30-SOD1G93A Tg, 85 days old); neurodegenerative (ALS); IP injection of ganciclovir given 24 hours before and during mp implantation surgery; behavioral testing (hindlimb reflex); "chronic and systemic injection of the nucleoside analog ganciclovir is lethal for CD11b-Tkmut30 transgenic mice, and ganciclovir is not highly diffusable within CNS tissue... To overcome this constraint, we proceeded with direct delivery of ganciclovir to the spinal cord via an osmotic pump connected to a cannula located in the intrathecal space." (p. 10240).

P9209 Ohta,Y., Kamiya,T., Nagai,M., Nagata,T., Morimoto,N., Miyazaki,K., Murakami,T., Kurata,T., Takehisa,Y., Ikeda,Y., Asoh,S., Ohta,S., Abe,K. Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis. Journal of Neuroscience Research 2008; 86(-13-):3028-3037. >>> TAT-GFP; TAT-Bcl-XL; CSF, artificial; CSF/CNS (intrathecal); Mice; mice (transgenic); 2001; 2004; 7, 28 days; Controls received mp w/ vehicle; stability verified by antiapoptotic effect at 7, 14, and 28 days at 37 degree Celsius (p. 3031); peptides; animal info (male, B6SJL, wt, G93A SOD1 Tg, 91 days old); neurodegenerative (ALS); behavioral testing (Rotarod test, wheel running test); "intrathecal infusion of TAT-infused proteins using an osmotic minipump is a better method of delivering therapeutic proteins into the spinal cord." (p. 3035).

P8908 Ishigaki,A., Aoki,M., Nagai,M., Warita,H., Kato,S., Kato,M., Nakamura,T., Funakoshi,H., Itoyama,Y. Intrathecal delivery of hepatocyte growth factor from amyotrophic lateral sclerosis onset suppresses disease progression in rat amyotrophic lateral sclerosis model. Journal of Neuropathology and Experimental Neurology 2007; 66(-11-):1037-1044. >>> Hepatocyte growth factor, recomb. human; PBS, sulfoxide; CSF/CNS (intrathecal, subarachnoid space); Rat (transgenic); 2002; 2004; 2, 4 weeks; Controls received mp w/ vehicle; dose-response (fig. 2); peptides; animal info (G93A Tg, 100 and 115 days old); neurodegenerative (ALS); "we examined the effects of continuous intrathecal delivery of human recombinant HGF (hrHGF) into Tg rats using implanted infusion pumps for selective and less invasive supply of HGF to the spinal cord." (p.1038).

P8852 Wang,H.Y., Ghosh,A., Baigude,H., Yang,C.S., Qiu,L.H., Xia,X.G., Zhou,H.X., Rana,T.M., Xu,Z.S. Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression. Journal of Biological Chemistry 2008; 283(-23-):15845-15852. >>> RNA, small interfering, modified; RNA, small interfering; PBS; CSF/CNS (intrathecal, subarachnoid space); Mice (transgenic); 1007D; 2004; 7, 28 days; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (Fig. 3); no stress (see pg. 15846, 15849); stability verified by 28 days in vivo (see Fig. 2); half-life (p. 15846) "short"; gene therapy; brain tissue distribution; animal info (SOD1G93A Tg); neurodegenerative (ALS); mp + catheter positioning confirmed; Target (SOD1); "when infused at disease onset at the therapeutic dose for 4 weeks, this siRNA slows disease progression without detectable adverse effects." The catheter was implanted between the L5 and L6 vertebra and connected to a primed Alzet osmotic pump with the PE50 tube. The catheter was stitched to the surface muscle, and the Alzet osmotic pumps were placed under the skin on the back of the mouse..

P8481 Locatelli,F., Corti,S., Papadimitriou,D., Fortunate,F., Del Bo,R., Donadoni,C., Nizzardo,M., Nardini,M., Salani,S., Ghezzi,S., Strazzer,S., Bresolin,N., Comi,G.P. Fas small interfering RNA reduces motoneuron death in amyotrophic lateral sclerosis mice. Annals of Neurology 2007; 62(-1-):81-92. >>> RNA, small interfering; CSF/CNS (intrathecal); Mice (transgenic); 2004; 4 weeks; Neurodegenerative (Amyotrophic Lateral Sclerosis); siRNA was used to silence the Fas receptor; animal info (C57BL/6, 90 days old); "Our study demonstrated that Fas silencing is able to interfere with motoneuron degeneration…providing new insights into the ALS pathogenesis and suggesting new possible strategies of molecular therapy…of ALS." p.91.

P8274 Sava,V., Reunova,O., Velasquez,A., Sanchez-Ramos,J. Can low level exposure to ochratoxin-A cause parkinsonism?. Journal of the Neurological Sciences 2006; 249(-1-):68-75. >>> Ochratoxin-A; Sodium bicarbonate; SC; Mice; 2 weeks; Controls received mp w/ vehicle; dose-response (fig. 3); comparison of IP injections vs. mp; no stress (see pg. 71); half-life (p. 71) 20-224 hours in various brain tissue; animal info (male, Swiss ICR, 22 grams); neurodegenerative (Amyotrophic Lateral Sclerosis, Parkinson's disease); mycotoxin; "Notably chronic exposure did not alter behavior or spontaneous locomotor activity, nor did it result in abnormal clasping or posturing of the limbs when handled by the tail." (p. 71).

P8266 Urushitani,M., bou Ezzi,S., Julien,J.P. Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-7-):2495-2500. >>> Antibody, mouse anti hSOD1; antibody, rabbit polyclonal anit-hSOD1-FITC; Saline; CSF/CNS; Mice; 2004; 16, 28 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; stability verified by Western Blot w/ residual volume AB after 18 days infusion; brain tissue distribution; animal info (G93A SOD1, 85 days old); neurodegenerative (ALS).

P8258 Rosi,S., Vazdarjanova,A., Ramirez-Amaya,V., Worley,P.F., Barnes,C.A., Wenk,G.L. Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat. Neuroscience 2006; 142(-4-):1303-1315. >>> Endotoxin, LPS; memantine; CSF, artificial; SC; CSF/CNS (fourth ventricle); Rat; 2004; 2ML4; 28 days; Controls received mp w/ vehicle; no stress (see pg. 1308); multiple pumps per animal (2); animal info (male, F-344, 3 months old); neurodegenerative (Alzheimer's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, etc.).

P7621 Narai,H., Nagano,I., Ilieva,H., Shiote,M., Nagata,T., Hayashi,T., Shoji,M., Abe,K. Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SOD(G93A) transgenic mice. Journal of Neuroscience Research 2005; 82(-4-):452-457. >>> Insulin-like growth factor I, recomb. human; CSF, artificial; CSF/CNS (intrathecal, subarachnoid space, lumbar); Mice (transgenic); 2004; 5-10 weeks; Controls received mp w/ vehicle; dose-response (fig 1); long-term study; pumps replaced every 4 weeks; neurodegenerative (Amyotrophic Lateral Sclerosis); animal info (C57BL/6J, female); cannula used for IT placement.

P6916 Zhang,M., Li,J., Chakrabarty,P., Bu,B.T., Vincent,I. Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick type C mice. American Journal of Pathology 2004; 165(-3-):843-853. >>> Roscovitine; olomoucine; iso-olomoucine; DMSO; CSF/CNS; Mice; 1002; 2, 4 weeks; Pumps replaced every 2 weeks for 4 week infusions; enzyme inhibitor (CDK); neurodegenerative (Alzheimer's disease, Amyotrophic Lateral Sclerosis, Niemann-Pick Type C disease); lynch coil used to accomodate 75% DMSO.

P6730 Storkebaum,E., Lambrechts,D., Dewerchin,M., Moreno-Murciano,M.P., Appelmans,S., Oh,H., Van Damme,P., Rutten,B., Man,W.Y., De Mol,M., Wyns,S., Manka,D., Vermeulen,K., Van den Bosch,L., Mertens,N., Schmitz,C., Robberecht,W., Conway,E.M., Collen,D., Moons,L., Carmeliet,P., Carmeliet,P. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nature Neuroscience 2005; 8(-1-):85-92. >>> Vascular endothelial growth factor, recomb. rat; CSF/CNS; Rat; 2004; 100 days; Long-term study; pumps replaced every 28 days; ALZET brain infusion kit used; VEGF was cleared from CSF within 3h; "70-80% of VEGF in pumps remained active after 4 weeks."; neurodegenerative (Amyotrophic Lateral Sclerosis).

P6100 Feeney,S.J., Austin,L., Bennett,T.M., Kurek,J.B., Jean-Francois,M.J.B., Muldoon,C., Byrne,E. The effect of leukaemia inhibitory factor on SOD1 G93A murine amyotrophic lateral sclerosis. Cytokine 2003; 23(-4-5-):108-118. >>> Leukemia inhibitory factor; CSF/CNS (intrathecal); Mice (transgenic); 2004; 13 weeks; Comparison of SC injections vs. IT mp; long-term study; pumps replaced every 4 weeks; ALZET brain infusion kit 1 used (per Dr. Feeney); used the BIK for the IT infusion; glued and sutured the cannula in place; "All mice that entered the study recovered from the surgical procedure and appeared to have no adverse effects." (p. 111); neurodegenerative (Amyotrophic Lateral Sclerosis).

P4452 Li,M., Ona,V.O, Guégan,C, Chen,M, Jackson-Lewis,V, Andrews,L.J., Olszewski,A.J, Stieg,P.E, Lee,J.-P, Przedborski,S, Friedlander,R.M. Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 2000/4/14; 288(-14-):335-339. >>> zVAD-fmk; DMSO; Pipes; CSF/CNS; Mice (transgenic); 56 days; Controls received mp w/vehicle; pumps replaced after 28 days; zVAD-fmk is a broad caspase inhibitor; also called N-benzyloxycarbonyl-Val-Asp- fluoromethylketone; neurodegenerative (Amyotrophic Lateral Sclerosis).

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3. Ataxia Telangiectasia

P6477 Browne,S.E., Roberts,LJ II, Dennery,P.A., Doctrow,S.R., Beal,M.F., Barlow,C., Levine,R.L. Treatment with a catalytic antioxidant corrects the neurobehavioral defect in ataxia-telangiectasia mice. Free Radical Biology and Medicine 2004; 36(-7-):938-942. >>> EUK-189; Mannitol; SC; Mice; 2004; 56, 84 days; Controls received mp w/ vehicle; long-term study; pumps replaced every 28 days; no stress (see pg.941); cancer (thymoma); EUK-189 is a synthetic catalytic antioxidant w/ both catalase&superoxide dismutase activities; neurodegenerative (ataxia telangiectasia).

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4. Huntington's Disease

Q0821 Zhu,S., Zhang,Y., Bai,G., Li,H. Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington's disease. Cell Death&Disease 2011; 2(-;-):U38-U41. >>> Letrozole; Propylene glycol; SC; Mice; 1002; 13 days; Controls received mp w/ vehicle; animal info (male, C57BL/6, ArKO, ArWT); enzyme inhibitor (aromatase).

Q0814 Cho,K.J., Lee,B.I., Cheon,S.Y., Kim,H.W., Kim,H.J., Kim,G.W. INHIBITION OF APOPTOSIS SIGNAL-REGULATING KINASE 1 REDUCES ENDOPLASMIC RETICULUM STRESS AND NUCLEAR HUNTINGTIN FRAGMENTS IN A MOUSE MODEL OF HUNTINGTON DISEASE. Neuroscience 2009; 163(-4-):1128-1134. >>> Antibody, anti-Ask1; CSF/CNs (striatum, intra-); Mice (transgenic); 4 weeks; Controls received mp w/ rabbit IgG or pre-immune Ask1 antibody); animal info (8-12 wks old, R6/2 HD male tg); neurodegenerative (Huntington's disease); behavioral testing (rotarod test); pump infused at a rate of 1 ul/hr.

Q0693 Rohe,M., Synowitz,M., Glass,R., Paul,S.M., Nykjaer,A., Willnow,T.E. Brain-Derived Neurotrophic Factor Reduces Amyloidogenic Processing through Control of SORLA Gene Expression. Journal of Neuroscience 2009; 29(-49-):15472-15478. >>> Brain-derived neurotrophic factor; CSF, artificial; CSF/CNS (hippocampus); Mice; 1007D; 7 days; Controls received mp w/ vehicle; animal info (BNDF -/-); ALZET brain infusion kit 2 used; neurodegenerative (Alzheimer's disease, Huntington's disease).

Q0499 Puerta,E., Hervias,I., Barros-Minones,L., Jordan,J., Ricobaraza,A., Cuadrado-Tejedor,M., Garcia-Osta,A., Aguirre,N. Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF. NEUROBIOLOGY OF DISEASE 2010; 38(-2-):237-245. >>> Nitropropionic acid, 3-; SC; Rat; 2ML1; 5 days; Animal info (male, Lewis, 290-340 g.); neurodegenerative (Huntington's Disease).

Q0428 Hathorn,T., Snyder-Keller,A., Messer,A. Nicotinamide improves motor deficits and upregulates PGC-1alpha and BDNF gene expression in a mouse model of Huntington's disease. NEUROBIOLOGY OF DISEASE 2011; 41(-1-):43-50. >>> Nicotinamide; SC; Mice; 2004; 10 weeks; Controls received mp w/saline; animal info (male, female, B6.HDR6/1, 8 wks old); pumps replaced after 5 weeks; long-term study; neurodegenerative (Huntington's disease); behavioral testing (open field testing, rotarod performance, balance beam).

P9837 Yang,L.C., Calingasan,N.Y., Thomas,B., Chaturvedi,R.K., Kiaei,M., Wille,E.J., Liby,K.T., Williams,C., Royce,D., Risingsong,R., Musiek,E.S., Morrow,J.D., Sporn,M., Beal,M.F. Neuroprotective Effects of the Triterpenoid, CDDO Methyl Amide, a Potent Inducer of Nrf2-Mediated Transcription. PLoS One 2009; 4(-6-):U87-U99. >>> MPTP; nitropropionic acid, 3-; PBS; SC; Rat; mice; 2004; 2ML1; 7, 28 days; Animal info (male, C57BL/6, 3 months old, 25-30 g., male, Lewis, 3 months old, 250-300 g.); neurodegenerative (Parkinson's, Huntington's Disease).

P9556 Yang,L.C., Calingasan,N.Y., Wille,E.J., Cormier,K., Smith,K., Ferrante,R.J., Beal,M.F. Combination therapy with Coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's Diseases. Journal of Neurochemistry 2009; 109(-5-):1427-1439. >>> MPTP; nitropropionic acid, 2-; PBS; SC; Rat; mice; 2004; 2ML1; ; Animal info (male, C57BL/6, 25-30g, Lewis 260-300g); neurodegenerative (Parkinson's, Hungtington's disease).

P9305 Park,J.E., Lee,S.T., Im,W.S., Chu,K., Kim,M. Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington's disease. Neuroscience Letters 2008; 448(-1-):143-147. >>> Nitropropionic acid, 3-; PBS; SC; Rat; 2ML1; 5 days; Animal info (male, Lewis, 12 wks old, 300-320 g.); neurodegenerative (Huntington's Disease).

P8922 Escartin,C., Boyer,F., Bemelmans,A.P., Hantraye,P., Brouillet,E. IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats. Neuroscience Letters 2007; 425(-3-):167-172. >>> Insulin-like growth factor I; nitropropionic acid, 3-; Acetic acid; BSA; SC; Rat; 2001; 2ML1; 5 days; Controls received mp w/ vehicle; functionality of mp verified by plasma glucose; dose-response (fig. 1, pg. 169); ALZET brain infusion kit used; animal info (Lewis, 400 g.); neurodegenerative (Huntington's Disease).

P8899 Jacquard,C., Trioulier,Y., Cosker,F., Escartin,C., Bizat,N., Hantraye,P., Cancela,J.M., Bonvento,G., Brouillet,E. Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation. FASEB Journal 2006; 20(-7-):U322-U336. >>> Nitropropionic acid, 3-; Water, deionized; NaOH; Phosphate buffer; SC; Rat; 2ML1; 6 days; Controls received empty mp; dose-response (fig.2); animal info (male, Lewis, 320-350 g., 12 wks old); neurodegenerative (Huntington's Disease).

P8801 Lee,S.T., Park,J.E., Kim,D.H., Kim,S., Im,W.S., Kang,L., Jung,S.H., Kim,M.W., Chu,K., Kim,M. Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease. Brain Research 2008; 1194(-;-):130-137. >>> Nitropropionic acid, 3-; PBS; NaOH; SC; Rat; 2ML1; 5 days; Animal info (male, Lewis, 300-320g., 12 wks. old); neurodegenerative (Huntington's disease).

P8626 Cho,S.R., Benraiss,A., Chmielnicki,E., Samdani,A., Economides,A., Goldman,S.A. Induction of neostriatal neurogenesis slows disease progression in a transgenic murine model of Huntington disease. Journal of Clinical Investigation 2007; 117(-10-):2889-2902. >>> Ara-C; Saline; CSF/CNS; Mice (transgenic); 1002; 4 weeks; Controls received mp w/ vehicle; pumps replaced after 2 weeks; ALZET brain infusion kit 3 used; animal info (R6/2, wt, 5-9 weeks old); neurodegenerative (Huntington's disease).

P8115 Lee,S.T., Chu,K., Park,J.E., Kang,L., Ko,S.Y., Jung,K.H., Kim,M. Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease. Brain Research 2006; 1118(-;-):199-207. >>> Nitropropionic acid, 3-; PBS; NaOH; SC; Rat; 2ML1; 4, 5 days; Animal Info (male, Sprague-Dawley, 220-240g.); neurodegenerative (Huntington's disease).

P8039 Woodruff,T.M., Crane,J.W., Proctor,L.M., Buller,K.M., Shek,A.B., de Vos,K., Pollitt,S., Williams,H.M., Shiels,I.A., Monk,P.N., Taylor,S.M. Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB Journal 2006; 20(-9-):1407-1417. >>> Nitropropionic acid, 3-; PBS; sodium hydroxide; SC; Rat; 2ML1; 7 days; Animal info (male, Lewis); neurodegenerative (Huntington's disease).

P7909 Picconi,B., Passino,E., Sgobio,C., Bonsi,P., Barone,I., Ghiglieri,V., Pisani,A., Bernardi,G., mmassari-Teule,M., Calabresi,P. Plastic and behavioral abnormalities in experimental Huntington's disease: A crucial role for cholinergic interneurons. NEUROBIOLOGY OF DISEASE 2006; 22(-1-):143-152. >>> Nitropropionic acid, 3-; Water, distilled; NaOH; SC; Rat; 2ML4; 5 days; Controls received emtpy mp; neurodegenerative (Huntington's disease); animal info (male, Lewis, 340-370 g, 12 weeks old).

P7110 Ona,V.O, Li,M.W., Vonsattel,J.P.G., Andrews,L.J., Khan,S.Q., Chung,W.M., Frey,A.S., Menon,A.S., Li,X.J., Stieg,P.E, Yuan,J., Penney,J.B., Young,A.B., Cha,J.H.L., Friedlander,R.M. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 1999; 399(--):263-267. >>> zVAD-fmk; zFA-fmk; CSF/CNS; Mice; 4 weeks; Controls received mp w/ zFA-fmk; enzyme inhibitor (caspase).

P7106 McBride,J.L, During,M.J, Wuu,J, Chen,E.Y, Leurgans,S.E., Kordower,J.H. Structural and functional neuroprotection in a rat model of Huntington's disease by viral gene transfer of GDNF. Experimental Neurology 2003; 181(--):213-223. >>> Nitropropionic acid, 3-; SC; Rat; 2ML4; 6 days; Neurodegenerative (huntington's disease).

P7053 Zucker,B., Ludin,D.E., Gerds,T.A., Luecking,C.H., Landwehrmeyer,G.B., Feuerstein,T.J. Gabapentin-lactam, but not gabapentin, reduces protein aggregates and improves motor performance in a transgenic mouse model of Huntington's disease. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2004; 370(-2-):131-139. >>> Gabapentin-lactam; gabapentin; Isobutanol; saline; SC; Rat; mice (transgenic); 2002; 4-8 weeks; Controls received mp w/ vehicle, or no treatment; functionality of mp verified by residual volume; long-term study; pumps replaced every 2 weeks; no stress (see pg. 137); half-life (pg. 134, 136) approx. 2 hours; "The continuous application of both GBP-L and of GBP by ALZET pumps have maintained the plasma levels so that the actions of these drugs at their targets in the CNS were not interrupted due to their rather short half-lives." (pg. 138); neurodegenerative (huntington's disease).

P6937 Blum,D., Gall,D, Cuvelier,L., Schiffmann,S.N. Topological analysis of striatal lesions induced by 3-nitropropionic acid in the Lewis rat. Neuropharmacology and Neurotoxicology 2001; 12(-8-):1769-1772. >>> Nitropropionic acid, 3-; PBS; SC; Rat; 2ML1; 5 days; Neurodegenerative (Huntington's Disease).

P6936 Dautry,C, Vaufrey,F, Brouillet,E., Bizat,N, Henry,P.G, Conde,F., Bloch,G., Hantraye,P. Early N-Acetylaspartate Depletion is a Marker of Neuronal Dysfunction in Rats and Primates Chronically Treated With the Mitochondrial Toxin 3-Nitropropionic Acid. Journal of Cerebral Blood Flow and Metabolism 2000; 20(--):789-799. >>> Nitropropionic acid, 3-; SC; Rat; 2ML4; 3,5 days; Controls received empty mp; neurodegenerative (Huntington's Disease).

P6935 Brouillet,E., Jenkins,B.G., Hyman,B.T., Ferrante,R.J., Kowall,N.W., Srivastava,R., Roy,D.S., Rosen,B.R., Beal,M.F. Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J.Neurochem. 1993/1; 60(-1-):356-359. >>> Nitropropionic acid, 3-; Water, deionized; NaOH; Rat; 2ML4; 1 month; Neurodegenerative (Huntington's disease).

P6934 Lastres-Becker,I., Bizat,N., Boyer,F., Hantraye,P., Fernandez-Ruiz,J., Brouillet,E. Potential involvement of cannabinoid receptors in 3-nitropropionic acid toxicity in vivo. NeuroReport 2004; 15(-15-):2375-2379. >>> Nitropropionic acid, 3-; SC; Rat; 2ML1; 5 days; Neurodegenerative (Huntington's disease).

P6932 Escartin,C., Boyer,F., Bemelmans,A.P., Hantraye,P., Brouillet,E. Insulin growth factor-I protects against excitotoxicity in the rat striatum. NeuroReport 2004; 15(-14-):2251-2254. >>> Insulin-like growth factor, recomb. human; BSA; acetic acid; CSF/CNS; Rat; 1003D; 2 days; ALZET brain infusion kit; neurodegenerative (Huntington's disease); dental cement used.

P6910 Jenkins,B.G., Brouillet,E., Chen,Y.C., Schulz,J.B., Kirschner,P. Non-Invasive Neurochemical Analysis of Focal Excitotoxic Lesions in Models of Neurodegenerative Illness Using Spectroscopic Imagine. Journal of Cerebral Blood Flow and Metabolism 1996; 16(--):450-461. >>> Nitropropionic acid, 3-; azide, sodium; SC; Rat; 2 weeks; Neurodegenerative (Huntington's disease, Parkinson's disease).

P6893 Bizat,N, Hermel,J.M., Humbert,S, Jacquard,C., Creminon,C., Escartin,C., Saudou,F, Krajewski,S., Hantraye,P., Brouillet,E. In Vivo Calpain/Caspase Cross-talk during 3-Nitropropionic Acid-induced Striatal Degeneration. Journal of Biological Chemistry 2003; 278(-44-):43245-43253. >>> Nitropropionic acid, 3-; calpain inhibitor I; DMSO; PBS; SC; CSF/CNS; Rat; 2001; 2ML1; 1-5 days; Controls received mp w/ vehicle or sham operation; enzyme inhibitor (succinate dehydrogenase); ALZET brain infusion kit used; multiple pumps per animal (2); 40% DMSO used for calpain inhibitor I; neurodegenerative (Huntington's disease).

P6881 Guyot,M.C., Hantraye,P., Dolan,R., Palfi,S., Maziere,M., Brouillet,E. Quantifiable bradykinesia, gait abnormalities and Huntington's disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid. Neuroscience 1997/7; 79(-1-):45-56. >>> Nitropropionic acid, 3-; Rat; 2ML4; 1 month; Controls received mp w/ saline; comparison of IP injections vs. mp; stress/adverse reaction: (see pg. 47) 5 animals with 3NP and mp and 4 animals with 3NP IP injections died due to toxicity of agent, no animals w/ saline mp died or had any adverse effects; toxicology; neurodegenerative (Huntington's disease).

P6770 Canals,J.M., Pineda,J.R., Torres-Peraza,J.F., Bosch,M., Martin-Ibanez,R., Munoz,M.T., Mengod,G., Ernfors,P., Alberch,J. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. Journal of Neuroscience 2004; 24(-35-):7727-7739. >>> Brain-derived neurotrophic factor; PBS; CSF/CNS (striatum); Mice (transgenic); 2001; 1 week; Controls received mp w/ vehicle; peptides; neurodegenerative (Huntington's disease).

P6441 Blum,D., Galas,M.G., Cuvelier,L., Schiffmann,S.N. Chronic intoxication with 3-nitropropionic acid in rats induces the loss of striatal dopamine terminals without affecting nigral cell viability. Neuroscience Letters 2004; 354(-3-):234-238. >>> Nitropropionic acid, 3-; PBS; NAOH; SC; Rat; 2ML1; 5 days; Enzyme inhibitor (succinate dehydrogenase); neurodegenerative (Huntington's disease); 3NP pH was adjusted to 7.4; "chronic intoxication with 3NP leads to alterations in striatal dopamine terminals similar to those found in HD patients and transgenic models." p.237.

P6179 Mittoux,V., Quary,S, Monville,C, Lisovoski,F, Poyot,T, Conde,F., Escartin,C., Robichon,R. Corticostriatopallidal Neuroprotection by Adenovirus-Mediated Ciliary Neurotrophic Factor Gene Transfer in a Rat Model of Progressive Striatal Degeneration. Journal of Neuroscience 2002; 22(-11-):4478-4486. >>> Nitropropionic acid, 3-; Water, deionized; NaOH; SC; Rat; 2ML4; 5,16 days; Controls received mp w/ nothing; gene therapy; neurodegenerative (Huntington's disease); behavioral testing; 3NP had a pH of 7.4.

P5908 Bizat,N., Hermel,J.M., Boyer,F., Jacquard,C., Creminon,C., Ouary,S., Escartin,C., Hantraye,P., Krajewski,S., Brouillet,E. Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate: Implications for Huntington's disease. Journal of Neuroscience 2003; 23(-12-):5020-5030. >>> Nitropropionic acid, 3-; calpain inhibitor-1; PBS; DMSO; SC; CSF/CNS; Rat; 2001; 2ML1; 5 days; ALZET brain infusion kit 1 used; neurodegenerative (Huntington's disease); 3-NP was infused using the 2ML1,&the CI-1 was delievered ICV using the 2001; CI-1 was dissolved in PBS&40% DMSO; pumps implanted simultaneously.

P5599 Sanchez,I., Mahlke,C., Yuan,J.Y. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature 2003; 421(-6921-):373-379. >>> Dye, Congo Red; PBS; DMSO; CSF/CNS; Mice (transgenic); 2004; 28 days; Controls received mp w/ vehicle; ALZET brain infusion kit 2 used (confirmed by Dr. Sanchez); neurodegenerative (Huntington's disease); 2% DMSO used.

P5504 Blum,D., Galas,M.C., Gall,D., Cuvelier,L., Schiffmann,S.N. Striatal and cortical neurochemical changes induced by chronic metabolic compromise in the 3-nitropropionic model of Huntington's disease. NEUROBIOLOGY OF DISEASE 2002; 10(-3-):410-426. >>> Nitropropionic acid, 3-; PBS; SC; Rat; 2ML1; 1, 2, 3, 4, 5 days; Neurodegenerative (Huntington's disease); neurotoxicity.

P5367 Sun,Z., Xie,J., Reiner,A. The differential vulnerability of striatal projection neurons in 3-nitropropionic acid-treated rats does not match that typical of adult-onset Huntington's disease. Experimental Neurology 2002; 176(-1-):55-65. >>> Nitropropionic acid, 3-; SC; Rat; 28 days; Neurodegenerative (Huntington's disease).

P5325 Blum,D., Gall,D., Galas,M.C., d'Alcantara,P., Bantubungi,K., Schiffmann,S.N. The adenosine A1 receptor agonist adenosine amine congener exerts a neuroprotective effect against the development of striatal lesions and motor impairments in the 3-nitropropionic acid model of neurotoxicity. Journal of Neuroscience 2002; 22(-20-):9122-9133. >>> Haloperidol; Olanzapine; Sertindole;; Saline; HCl; Tartaric acid;; SC;; rat;; 2ML4;; 5 days; Controls received mp w/ vehicle; functionality of mp verified by drug plasma levels (" ... the continuous infusion via mini-pumps is certainly the most relevant way to mimic conditions of treatment in clinic." p. 302); dose response (p. 302); comparison of SC injections vs. mp; half-life (p. 293); compared acute, subchronic (3 day) vs chronic (21 day) treatment; oral administration also examined; antipsychotics; schizophrenia; neurodegenerative (Huntington's disease); Olanzapine and sertindole were dissolved in a minimum amount of dilute HCl before dilution in saline; Haloperidol dissolved in minimal amount of dilute tartaric acid before final dilution in 0.9% saline;.

P4813 Vis,J.C., Verbeek,M.M., de Waal,R.M.W., ten Donkelaar,H.J., Kremer,B. The mitochondrial toxin 3-nitropropionic acid induces differential expression patterns of apoptosis-related markers in rat striatum.. Neuropathology and Applied Neurobiology 2001; 27(--):68-76. >>> Nitropropionic acid, 3-;; Water;; SC;; rat;; 4 weeks;; Controls received mp w/ saline; neurodegenerative (Huntington's disease).

P4756 Leventhal,L, Sortwell,C.E, Hanbury,R, Collier,T.J., Korkower,J.H, Palfi,S. Cyclosporin A protects striatal neurons in vitro and in vivo from 3-nitropropionic acid toxicity.. The Journal of Comparative Neurology 2000; 425(--):471-478. >>> Nitropropionic acid, 3-; PBS;; SC;; rat;; 2004;; 7 days;; Controls received mp w/ vehicle; toxicology; 3-nitro-propionate also called 3-nitropropionic acid (3NP); 3NP is a mitochondrial toxin; neurodegenerative (Huntington's disease).

P4670 Ouary,S, Bizat,N, Altairac,S., Menetrat,H, Mittoux,V., Conde,F., Hantraye,P., Brouillet,E. Major strain differences in response to chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid in rats: Implications for neuroprotection studies.. Neuroscience 2000; 97(-3-):521-530. >>> Nitropropionic acid, 3-;; Saline;; SC; rat; 2ML4;; 5 days;; Controls received empty pumps; comparison of IP injections vs. mp; neurodegenerative (Huntington's disease); mitochondrial toxin; neuroprotection..

P1860 Rieke,G.K., Smith,J., Idusuyi,O.B., Semenya,J., Howard,R., Williams,S. Chronic intrastriatal L-pyroglutamate: neuropathology and neuron sparing like Huntington's Disease. Exp.Neurol. 1989; 104(--):147-154. >>> Pyroglutamate, L-; Saline; CSF/CNS (striatum); rat; 2002; 9-14 days; Neurodegenerative (Huntington's disease).

P1526 Rieke,G.K., Scarfe,A.D., Hunter,J.F. L-pyroglutamate: an alternate neurotoxin for a rodent model of Huntington's disease. Brain Res.Bull. 1984; 13(--):443-456. >>> Pyroglutamate, L-; Millinog's phosphate buffer; CSF/CNS (caudate putamen); mice; 2002; no duration posted; controls received mp with vehicle; stress/adverse reaction: (pg. 450) small necrotic region seen around tip of implanted cannula in control animals; not actually a pump paper; authors' previous pump research mentioned in discussion section (pg. 450&454); neurodegenerative (Huntington's disease).

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5. Multiple Sclerosis

P9207 Nizri,E., Irony-Tur-Sinai,M., Faranesh,N., Lavon,I., Lavi,E., Weinstock,M., Brenner,T. Suppression of neuroinflammation and immunomodulation by the acetylcholinesterase inhibitor rivastigmine. Journal of Neuroimmunology 2008; 203(-1-):12-22. >>> Rivastigmine; Saline; SC; Mice; 2004; 21, 28 days; Controls received mp w/ vehicle; comparison of SC injections vs. mp; half-life (p. 13) 4 hours; enzyme inhibitor (acetylcholinesterase); animal info (female, C57BL/6, 8 wks old, EAE); neurodegenerative (multiple sclerosis); behavioral testing (Morris water maze); "Delivery of rivastigmine by mini-osmotic pumps to ensure more uniform + continuous AChE inhibition was more effective than single daily doses and reduced disease severity and cummulative score by 73% and 72%, respectively." (p.17).

P8861 Wang,J.Y., Takeuchi,H., Sonobe,Y., Jin,S., Mizuno,T., Miyakawa,S., Fujiwara,M., Nakamura,Y., Kato,T., Muramatsu,H., Muramatsu,T., Suzumura,A. Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2008; 105(-10-):3915-3920. >>> Midkine; PBS; SC; Mice; 1002; 14 days; Controls received mp w/ vehicle; animal info (Mk -/-); neurodegenerative (multiple sclerosis); midkine (MK) is a heparin binding growth factor.

P8651 Matute,C., Torre,I., Perez-Cerda,F., Perez-Samartin,A., Alberdi,E., Etxebarria,E., Arranz,A.M., Ravid,R., Rodriguez-Antigueedad,A., Saanchez-Goomez,M.V., Domercq,M. P2X7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. Journal of Neuroscience 2007; 27(-35-):9525-9533. >>> Adenosine triphosphate-gamma-S; adenosine triphosphate, 2', 3'-O-(benzoyl-4-benzoyl)-; adenosine triphosphate, oxidized; dye, brilliant blue G; Saline; PBS, sterile; CSF/CNS (optic nerve); Rabbit; 1003D; 3 days; Controls received mp w/ vehicle; neurodegenerative (multiple sclerosis).

P8629 Fitzgerald,D.C., Ciric,B., Touil,T., Harle,H., Grammatikopolou,J., Das Sarma,J., Gran,B., Zhang,G.X., Rostami,A. Suppressive effect of IL-27 on encephalitogenic Th17 cellsAnd the effector phase of experimental autoimmune encephalomyelitis1. Journal of Immunology 2007; 179(-5-):3268-3275. >>> Interleukin-27, recomb. mouse; PBS; SC; Mice; 7 days; Controls received mp w/ vehicle; animal info (female, C57BL/6, 8-12 wks old); neurodegenerative (multiple sclerosis); "initially we tested i.p. injection of recombinant carrier-free IL-27 however, these experiments did not provide reproducible findings. To achieve continual, consistent delivery of cytokine throughout the treatment period, we implanted osmotic minipumps." (p. 3273); immunology.

P8509 Bhasin,M., Wu,M.Z., Tsirka,S.E. Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis. BMC IMMUNOLOGY 2007; 8(--):U1-U16. >>> Tuftsin; macrophage inhibitory factor; SC; Mice; 2002; 30 days; Controls received mp w/ PBS; pumps replaced after 14 days; enzyme inhibitor (ACE); immunology; peptides; animal info (female, tPA -/- or wt, 6-10 weeks old); neurodegenerative (Multiple Sclerosis).

P8258 Rosi,S., Vazdarjanova,A., Ramirez-Amaya,V., Worley,P.F., Barnes,C.A., Wenk,G.L. Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat. Neuroscience 2006; 142(-4-):1303-1315. >>> Endotoxin, LPS; memantine; CSF, artificial; SC; CSF/CNS (fourth ventricle); Rat; 2004; 2ML4; 28 days; Controls received mp w/ vehicle; no stress (see pg. 1308); multiple pumps per animal (2); animal info (male, F-344, 3 months old); neurodegenerative (Alzheimer's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, etc.).

P7856 Liu,Y.R., Liu,J., Tetzlaff,W., Paty,D.W., Cynader,M.S. Biliverdin reductase, a major physiologic cytoprotectant, suppresses experimental autoimmune encephalomyelitis. Free Radical Biology and Medicine 2006; 40(-6-):960-967. >>> CSF, artificial; CSF, artificial; gentamicin; CSF/CNS (intrathecal, subarachnoid space); Rat; 2004; ; Immunology; animal info (male, Lewis, 200g., EAE (experimental autoimmune encephalomyelitis)); freshly prepared antioxidant enzymes were delivered intrathecally once daily through the PE tubing via Hamilton syringe on days 13-17, mp then reconnected to keep tube clear; multiple sclerosis model; pump used to maintain catheter patency.

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6. Niemann-Pick Type C Disease

P6916 Zhang,M., Li,J., Chakrabarty,P., Bu,B.T., Vincent,I. Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick type C mice. American Journal of Pathology 2004; 165(-3-):843-853. >>> Roscovitine; olomoucine; iso-olomoucine; DMSO; CSF/CNS; Mice; 1002; 2, 4 weeks; Pumps replaced every 2 weeks for 4 week infusions; enzyme inhibitor (CDK); neurodegenerative (Alzheimer's disease, Amyotrophic Lateral Sclerosis, Niemann-Pick Type C disease); lynch coil used to accomodate 75% DMSO.

P5859 Camargo,F., Erickson,R.P., Garver,W.S., Hossain,G.S., Carbone,P.N., Heidenreich,R.A., Blanchard,J. Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease. Life Sci 2001; 70(-2-):131-142. >>> Cyclodextrin, 2-hydroxypropyl-ß-; Saline, sterile; CSF/CNS; Mice (knockout); 2004; 28 days; stress/adverse reaction: (see pg.139) mice were active&broke the cemented cannulae away from the skull; ALZET brain infusion kit 2 used (per Dr. Erickson); 2-Hydroxypropyl-ß-cyclodextrin is (HPBCD); methylene blue dye infused (probably not by pump) after cyclodextrin infusion to confirm the intraventricular location; delivery route somewhat confusing - paper refers to the route alternately as intrathecal and intraventricular; neurodegenerative (Niemann-Pick Type C disease).

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7. Parkinson's Disease

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