| 1. |
- Mundt-Petersen, Ulrika, et al.
(författare)
-
Caspase inhibition increases embryonic striatal graft survival
- 2000
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 164:1, s. 112-120
-
Tidskriftsartikel (refereegranskat)abstract
- In transplants of embryonic striatal cells placed into the excitotoxically lesioned rat striatum (a model of Huntington's disease), as many as 60 to 90% of the grafted cells are believed to die. Caspase activation is part of a cascade of events that can lead to apoptosis. We investigated the effect of the caspase inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethylketone (Ac-YVAD-cmk) on grafted embryonic striatal cells in the excitotoxically lesioned or intact rat striatum. Female Sprague–Dawley rats were subjected to unilateral intrastriatal injection of quinolinic acid. After 10 days, rats received bilateral intrastriatal grafts from embryonic day 14 rat lateral ganglionic eminence. Rats were divided into the following groups: Ac-YVAD-cmk, pretreatment of the graft tissue with the caspase inhibitor (500 μM); and control, untreated control grafts. Rats were perfused 10 days or 5 weeks postgrafting. Brain sections were processed immunohistochemically using an antibody against the striatal neuron marker dopamine- and adenosine 3′,5′-monophosphate-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP-32). Adjacent sections were stained for acetylcholinesterase/cresyl violet cytochemistry and Fluoro-Jade cytochemistry, a marker for degenerating neurons. Total graft volume, P-zone volume, total number of neuron-like cells, and number of DARPP-32-positive cells were increased, compared to control, in the group receiving Ac-YVAD-cmk-treated graft tissue. Moreover, transplants injected into the intact striatum were found to be significantly smaller compared to transplants placed into the excitotoxically lesioned striatum. The Fluoro-Jade staining revealed ongoing cell death in transplants 10 days after intrastriatal implantation and that cell death was significantly reduced 5 weeks after grafting.
|
|
| 2. |
- Brundin, Patrik, et al.
(författare)
-
Grafts of Embryonic Dopamine Neurons in Rodent Models of Parkinson's Disease
- 1999
-
Ingår i: CNS regeneration: Basic Science and Clinical Applications. - 9780127050706 ; , s. 299-299
-
Bokkapitel (refereegranskat)abstract
- This chapter exemplifies rodent models of Parkinson's disease that have been used in transplantation studies and recounts basic transplantation methods. It describes morphological features of grafts containing dopamine neurons and focuses on the role of nigral grafts that are implanted homotopically in the mesencephalon, for example, near their location in the normal brain. The neurotoxin 6-hydroxydopamine (OHDA) is selectively taken up by catecholaminergic neurons and kills them through a mechanism that is still not fully elucidated, but may well include oxidative stress. When injected in adequate amounts into the brain, it can cause extensive and permanent damage to catecholaminergic neurons, such as those giving rise to the nigrostriatal pathway. The survival of dopamine neurons placed in a 6-OHDA denervated striatum is reflected by restoration of striatal dopamine levels to around 10 to 30% of normal. Examination of the ratio between levels of the dopamine metabolite DOPAC and dopamine reveals ratios that are 50 to 200% higher in grafted striata compared to normal, suggesting that the grafted neurons have an increased transmitter turnover
|
|
| 3. |
- Mundt-Petersen, Ulrika, et al.
(författare)
-
Infusional Therapies, Continuous Dopaminergic Stimulation, and Nonmotor Symptoms
- 2017
-
Ingår i: Parkinson’s: The Hidden Face Management and the Hidden Face of Related Disorders. - : Elsevier. - 0074-7742. - 9780128126035 ; 134, s. 1019-1044
-
Bokkapitel (refereegranskat)abstract
- Pump-based Parkinson (PD) therapies, including subcutaneous apomorphine infusion (CSA) and levodopa-carbidopa intestinal gel (LCIG), presently constitute the most effective pharmacological treatments available for advanced PD. These therapies are based on a more constant delivery of the dopaminergic drug resulting in a more continuous dopaminergic stimulation and a more stable treatment effect. This can be detected as reduction of time in off, reduction of dyskinesia frequency and severity, as well as increase of time in on without troublesome dyskinesias. A number of open-label studies now suggest that also the nonmotor PD symptomatology can improve under CSA and LCIG therapy. The most consistent improvements are seen concerning sleep, mood, and apathy, gastrointestinal symptoms, and urological symptoms. But also cardiovascular symptoms, perception, attention, and sexual function might show beneficial effects when moving from conventional therapies to pump treatment. Further there might be negative influences on some parts of the nonmotor symptomatology through side effects of CSA and LCIG therapy. In this chapter, we review the present knowledge about these aspects of the pump-based therapies. This information might be valuable when deciding on advanced therapy for individual patients.
|
|
| 4. |
|
|
| 5. |
- Mundt-Petersen, Ulrika, et al.
(författare)
-
Pretreatment with MK-801 or the lazaroid U-83836E does not enhance striatal graft survival
- 2000
-
Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 9:1, s. 73-78
-
Tidskriftsartikel (refereegranskat)abstract
- A large proportion of grafted striatal neurons die, and mechanisms by which they succumb may involve excitotoxicity and oxidative stress. We investigated the effects of pretreatment of the graft tissue with the N-methyl-D-aspartate (NMDA) receptor antagonist (+)dizocilpine hydrogen maleate (MK-801) and lipid peroxidation inhibitor lazaroid U-83836E on the survival of transplanted striatal neurons. Neither compound increased the survival of grafts, suggesting that NMDA-related excitotoxicity or oxidative stress may not be primary mediators of cell death in striatal grafts.
|
|
| 6. |
- Timpka, Jonathan, et al.
(författare)
-
Continuous dopaminergic stimulation therapy for Parkinson's disease - Recent advances
- 2016
-
Ingår i: Current Opinion in Neurology. - 1350-7540. ; 29:4, s. 474-479
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose of review We aim to review the most interesting recent advances on the clinical aspects of continuous dopaminergic stimulation in Parkinson's disease. Recent findings Several large, open-label studies have presented data that are in line with the randomized controlled trial on L-dopa-carbidopa intestinal gel infusion, which shows that a continuous drug delivery can improve motor fluctuations and dyskinesia in patients with advanced Parkinson's disease. Furthermore, new extended-release formulations of L-dopa aim to stabilize plasma concentrations and thus reduce the degree of motor complications - despite a reduced number of daily doses. Transdermal rotigotine has been shown to be effective for specific subgroups of patients, although the general effect on nonmotor symptoms is still unclear. New products for L-dopa infusion are also at different stages of development, but the routes of administration are widely different: intrajejunal, subcutaneous, and oral. Summary The understanding of the mechanisms behind the complications of long-term L-dopa treatment is still not complete, but therapies aiming for continuous dopaminergic stimulation are already widely used in clinical practice and the evidence strength is improving. However, there is still an urgent need for both less invasive and less costly options in order to increase access to these therapies.
|
|
