An improved device for continuous intraventricular infusions prevents the introduction of pump-derived toxins and increases the effectiveness of NGF treatments

Vahlsing, H. Lee; Varon, Silvio; Hagg, Theo; Fass-Holmes, Barry; Dekker, Alain D.; Manley, Michael S.; Manthorpe, Marston

doi:10.1016/0014-4886(89)90125-8

Cited by 45 publications

(11 citation statements)

References 13 publications

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“…24 IGF-I dissolved in 10 mmol/L of HCl and sterile isotonic saline at a concentration of 8.3 mg/ml was loaded into miniosmotic pumps (model 1002; Alzet, Cupertino, CA) that had been partially dipped in paraffin wax to achieve a pumping rate of 0.125 l/hour (3 l/day) for 28 days. 25 Loaded pumps were primed in isotonic saline at 37°C for 24 hours before implantation. Mice assigned to receive IGF-I were anesthetized with pentobarbitone sodium (Nembutal, 40 mg/kg i.p.…”

Section: Methodsmentioning

confidence: 99%

Improved Contractile Function of the mdx Dystrophic Mouse Diaphragm Muscle after Insulin-Like Growth Factor-I Administration

Gregorevic

Plant

Leeding

et al. 2002

The American Journal of Pathology

108

102

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Limited knowledge exists regarding the efficacy of insulin-like growth factor I (IGF-I) administration as a therapeutic intervention for muscular dystrophies, although findings from other muscle pathology models suggest clinical potential. The diaphragm muscles of mdx mice (a model for Duchenne muscular dystrophy) were examined after 8 weeks of IGF-I administration (1 mg/kg s.c.) to test the hypothesis that IGF-I would improve the functional properties of dystrophic skeletal muscles. Force per cross-sectional area was ϳ49% greater in the muscles of treated mdx mice (149.6 ؎ 9.6 kN/m 2 ) compared with untreated mice (100.1 ؎ 4.6 kN/m 2 , P < 0.05), and maintenance of force over repeated maximal contraction was enhanced ϳ30% in muscles of treated mice (P < 0.05). Diaphragm muscles from treated mice comprised fibers with ϳ36% elevated activity of the oxidative enzyme succinate dehydrogenase, and ϳ23% reduction in the proportion of fast IId/x muscle fibers with concomitant increase in the proportion of type IIa fibers compared with untreated mice (P < 0.05). The data demonstrate that IGF-I administration can enhance the fatigue resistance of respiratory muscles in an animal model of dystrophin deficiency, in conjunction with enhancing energenic enzyme activity. As respiratory function is a mortality predictor in Duchenne muscular dystrophy patients, further evaluation of IGF-I intervention is recommended. (Am J

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Section: Methodsmentioning

confidence: 99%

Improved Contractile Function of the mdx Dystrophic Mouse Diaphragm Muscle after Insulin-Like Growth Factor-I Administration

Gregorevic

Plant

Leeding

et al. 2002

The American Journal of Pathology

108

102

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“…A flow-regulated mini-osmotic pump (Alzet model 2002) was connected to the cannula via 3.5 cm of polyethylene tubing. To prolong the effectiveness of the pump, we coated the bottom third of each pump in paraffin before implantation (Vahlsing et al, 1989). This served to reduce the flow rate of the pump from 12 l/d to ϳ9 l /d, making the pump effective for an additional 7 d. The pump was placed subcutaneously in the dorsal neck / back region, and it delivered either PBS, pH 7.2, or 2.5 S NGF (1 mg /ml in PBS).…”

Section: Methodsmentioning

confidence: 99%

Nerve Growth Factor Accelerates Seizure Development, Enhances Mossy Fiber Sprouting, and Attenuates Seizure-Induced Decreases in Neuronal Density in the Kindling Model of Epilepsy

Adams¹,

et al. 1997

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Recurrent seizure activity induced during kindling has been reported to produce a functional synaptic reorganization of the mossy fibers in the hippocampus. To date, it is unclear whether this kindling-induced growth is secondary to decreases in hilar neuron density, which are presumed to reflect hilar neuronal cell loss, or whether it is related specifically to an activationdependent plasticity. We recently demonstrated that blocking nerve growth factor (NGF) biological activity retards seizure development and inhibits the sprouting of mossy fibers. We now demonstrate that intraventricular administration of NGF itself accelerates the progression of kindling epileptogenesis, increases mossy fiber sprouting in the CA3 region and in the inner molecular layer (IML), but reduces seizure-induced decreases in hilar cell density. These findings provide support for a role of NGF in kindling and kindling-induced mossy fiber sprouting. In addition, the results dissociate this form of epileptogenesis from hilar cell loss or decreases in hilar cell density attributable to increases in hilar area, thereby supporting seizure-induced mossy fiber sprouting as being primarily attributable to the combined effects of neuronal activation and the activation-induced upregulation of growth factors.

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“…1A). Each cannula was connected to an Alzet 2002 mini-osmotic pump (Alza; partly coated with paraffin to reduce the flow rate from 0.5 to 0.2 1./hr) by a coiled reservoir (26). The reservoir was filled with vehicle (artificial cerebrospinal fluid with 1 mg of rat serum albumin per ml; Sigma A-6272) (n = 4) or vehicle containing recombinant human CNTF (5 x 103 Trophic Units/day or 1.5 pg/day) (n = 6) for a 14-day infusion.…”

Section: Methodsmentioning

confidence: 99%

Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo.

Hagg

Varon

1993

Proc. Natl. Acad. Sci. U.S.A.

211

102

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We have investigated the neuroprotective effects of recombinant human ciliary neurotrophic factor (CNTF) for injured dopaminergic neurons of the adult rat substantia nigra compacta. Fourteen days after a unilateral ansetion of the nigrostriatal pathway two-thirds of the neurons (identiffed by retograde labeling) had degenerated. In sharp contrast, 73% (a few cases, >90%) of this ceil loss was prevented by continuous infusion of CNTF close to the injured neurons. However, CNTF did not prevent the disappearance of the transmitter-synthesizing enzyme tyrosine hydroxylase.Thus, CNTF has potent neurotrophic effects for injured adult rat dopaminergic substantia nigra neurons, whose degeneration plays a major causative role in Parkinson disease.

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An improved device for continuous intraventricular infusions prevents the introduction of pump-derived toxins and increases the effectiveness of NGF treatments

Cited by 45 publications

References 13 publications

Improved Contractile Function of the mdx Dystrophic Mouse Diaphragm Muscle after Insulin-Like Growth Factor-I Administration

Improved Contractile Function of the mdx Dystrophic Mouse Diaphragm Muscle after Insulin-Like Growth Factor-I Administration

Nerve Growth Factor Accelerates Seizure Development, Enhances Mossy Fiber Sprouting, and Attenuates Seizure-Induced Decreases in Neuronal Density in the Kindling Model of Epilepsy

Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo.

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