A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology

Nikkhah, Guido; Olsson, Martin; Eberhard, Jakob; Bentlage, C; Cunningham, M G; Björklund, Anders

doi:10.1016/0306-4522(94)90007-8

Cited by 212 publications

(147 citation statements)

References 30 publications

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“…In Experiment 2, a total of 14 µg 6-OHDA (3.5 µg/µl free base in 0.02% L-ascorbic acid in 0.9% sterile saline) were injected into the striatum (AP = ±0.5 mm from bregma; ML = -3.2/-4.2 mm from bregma; DV = -5.0 mm from the dura surface; Tooth bar = 0.0; injection speed 1 µl/min). To give less damage to the brain, a glass capillary (outer diameter 60 -80 µm) was fitted onto the needle of a Hamilton syringe (Nikkhah et al, 1994). In order to protect NA fibers, the NA transporter blocker, desipramine (20 mg/kg, i.p.)…”

Section: Lesion Surgerymentioning

confidence: 99%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, studies of post-mortem PD brains have shown that not only DA neurons but also the noradrenergic (NA) neurons in the locus coeruleus degenerate, and that the NA neurodegeneration may be as profound, and also precede degeneration of the midbrain DA neurons. Previous studies in animal models of PD have suggested that loss of forebrain NA will add to the development of motor symptoms in animals with lesions of the nigrostriatal DA neurons, but the results obtained in rodents have been inconclusive due to the shortcomings of the toxin, DSP-4, used to lesion the NA projections. Here, we have developed an alternative double-lesion paradigm using injections of 6-OHDA into striatum in combination with intraventricular injections of a powerful NA immunotoxin, anti-DBH-Saporin, to eliminate the NA neurons in the brain.Animals with combined DA and NA lesions were more prone to develop L-DOPAinduced dyskinesia, even at low L-DOPA doses, and they performed significantly worse in tests of reflexive and skilled paw use, the stepping and staircase tests, compared to DA-only lesioned rats. Post-mortem analysis revealed that NA depletion did not affect the degree of DA depletion, or the loss of tyrosine hydroxylase-positive innervation in the striatum. Cell loss in the substantia nigra was similar in both single and double lesioned animals, showing that the worsening effect was not due to increased loss of nigral DA neurons. The results show that damage to the NA neurons in the central nervous system contributes to the development of motor impairments and the appearance of L-DOPAinduced dyskinesia in 6-OHDA lesioned rats, and provide support for the view that the development of motor symptoms and dyskinetic side effects in PD patients reflects the combined loss of midbrain DA neurons and NA neurons.3

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Section: Lesion Surgerymentioning

confidence: 99%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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“…Finally, a dorsal cut was performed through the midbrain to limit the tissue to the ventral third of the midbrain piece. The standard VM cell suspension that contained both DA and serotonin neuroblasts was performed as described previously (DA-wide group) (Nikkhah et al, 1994;Winkler et al, 1999;Kirik et al, 2001;Georgievska et al, 2004;Carlsson et al, 2006). In this dissection, the caudal cut was performed slightly caudal to the rhombencephalic isthmus to include the entire VM and most rostral part of the pontine raphe region in the final tissue piece processed for transplantation (see Fig.…”

Section: Cell Preparation and Transplantation Surgerymentioning

confidence: 99%

Serotonin Neuron Transplants Exacerbate l-DOPA- Induced Dyskinesias in a Rat Model of Parkinson's Disease

Carlsson¹,

Carta²,

et al. 2007

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“…The VM tissue was prepared into a single cell suspension following the procedure described earlier (Nikkhah et al, 1994, Winkler et al, 1999, Kirik et al, 2001, Georgievska et al, 2004.…”

Section: Transplantation Proceduresmentioning

confidence: 99%

Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia

Carlsson

Winkler

Lundblad

et al. 2006

Neurobiology of Disease

101

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In two recent double-blind clinical trials of fetal ventral mesencephalic cell transplants into the striatum in patients with Parkinson's disease (PD), a significant proportion of the grafted patients developed dyskinetic side effects, which were not seen in the sham operated patients.Comparison between dyskinetic and non-dyskinetic grafted patients in one of the trials suggested that an uneven pattern of striatal reinnervation might be the leading cause of the dyskinesias.Here we studied the importance of graft placement for the development of dyskinesias in parkinsonian rats. Abnormal involuntary movements resembling peak-dose dyskinesias seen in

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A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology

Cited by 212 publications

References 30 publications

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Serotonin Neuron Transplants Exacerbate l-DOPA- Induced Dyskinesias in a Rat Model of Parkinson's Disease

Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia

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