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- Blomqvist, Anders, 1949-, et al.
(författare)
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Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus
- 2000
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Ingår i: Brain. - 0006-8950 .- 1460-2156. ; 123:3, s. 601-619
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in the macaque monkey have identified a thalamic nucleus, the posterior portion of the ventral medial nucleus (VMpo), as a dedicated lamina I spinothalamocortical relay for pain and temperature sensation. The dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in primates enables its homologue to be identified in the human thalamus by immunohistochemical labelling for calbindin. We have now analysed in detail the cytoarchitectonic characteristics of VMpo and its relationship with immunoreactivity for calbindin, substance P and calcitonin gene-related peptide (CGRP) in the human thalamus. The area in the posterolateral thalamus in which dense calbindin-immunoreactive fibre terminations are present coincides nearly completely with a distinct region that contains small to medium-sized cells with round or oval shapes that are aggregated in clusters separated by cell sparse areas. This region, which we identify as VMpo, is located posteromedial to the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and centre median nuclei, lateral to the limitans and parafascicular nuclei and dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres enter VMpo from the spinal lemniscus and form large patches of dense terminal-like staining over clusters of VMpo neurons. A few of these clusters also display terminal-like substance P labelling. Small bursts of CGRP staining are intercalated between the calbindin-labelled clusters, but there is little or no overlap between these two markers. CGRP inmunoreactivity is also present over small, non-clustered neurons in the calbindin-negative area that separates VMpo from the VPL and VPM nuclei, which we denote as the posterior nucleus (Po). These observations provide a concise description of VMpo in the human thalamus. Further, they suggest that the lamina I spinothalamic tract fibres (represented by calbindin and probably also substance P immunoreactivity) and vagal-solitary-parabrachial afferents (represented by CGRP immunoreactivity) form closely related, but separate, termination fields that can be considered to represent different aspects of enteroceptive information regarding the physiological status of the tissues and organs of the body. The location of VMpo and the adjacent Po fits with clinical descriptions of the thalamic area from which pain, temperature and visceral sensations can be evoked by microstimulation, and where nociceptive and thermoreceptive neurons have been recorded in humans. It also corresponds to the area in which infarcts cause analgesia and thermoanaesthesia and can lead to the paradoxical development of central pain.
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- Brundin, Patrik, et al.
(författare)
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Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
- 2000
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Ingår i: Brain. - 1460-2156. ; 123, s. 1380-1390
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Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
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- Goadsby, PJ, et al.
(författare)
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Adenosine A(1) receptor agonists inhibit trigeminovascular nociceptive transmission
- 2002
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 125, s. 1392-1401
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Tidskriftsartikel (refereegranskat)abstract
- There is a considerable literature to suggest that adenosine A(1) receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A(1) receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperitoneally), and prepared for physiological monitoring. The superior sagittal sinus (SSS) was stimulated electrically, and linked units were recorded in the trigeminocervical complex. Post-stimulus histograms were constructed to analyse the responses and the effect of drug administration. Blood was sampled from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A(1) receptor agonist, GR79236 (3-100 mug/kg) had a dose-dependent inhibitory effect on SSS-evoked trigeminal activity. The maximal effect (80 +/- 6% reduction in probability of firing) was seen at 100 mug/kg. The neuronal inhibitory effect of GR79236 could be inhibited by the selective adenosine A(1) receptor antagonist DPCPX (300 mug/kg; P < 0.05). SSS stimulation increased cranial CGRP levels from 33 &PLUSMN; 2 pmol/l (n = 6) to 64 &PLUSMN; 3 pmoll, an effect substantially reduced by pre-treatment with GR79236 (30 μg/kg; P < 0.01). The selective low efficacy adenosine A(1) receptor agonist, GR190178 (30-1000 mug/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion. In this model of trigeminovascular nociception, adenosine A(1) receptor activation leads to neuronal inhibition without concomitant vasoconstriction, suggesting a novel avenue for the treatment of migraine and cluster headache.
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- Jacobsson, Johan, et al.
(författare)
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Superoxide dismutase in CSF from amyotrophic lateral sclerosis patients with and without CuZn-superoxide dismutase mutations
- 2001
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 124:7, s. 1461-1466
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in CuZn-superoxide dismutase (CuZn-SOD) have been linked to familial amyotrophic lateral sclerosis (ALS), and motor neurone death is caused by the gain of a toxic property of the mutant protein. Here we determined amounts, activity and molecular forms of CuZn-SOD in CSF from ALS patients carrying the D90A and other CuZn-SOD mutations and patients without such mutations. There were no differences in amount of protein and enzymic activities of CuZn-SOD between 37 neurological controls, 54 sporadic and 12 familial ALS cases, and 10 cases homozygous for the D90A mutation. Three cases heterozygous for the A89V, S105L and G114A CuZn-SOD mutations showed low amounts of CuZn-SOD. There was no evidence for accumulation of inactive protein in any of the groups. Immunoblots showed no evidence for the presence of any precipitates or other molecular forms of CuZn-SOD with higher molecular weight in the groups. About 25% of the CuZn-SOD subunits in CSF from controls shows an N-terminal truncation. This truncated portion does not differ between controls and ALS groups not carrying CuZn-SOD mutations, but is 70% larger in samples from D90A homozygous ALS patients. The findings suggest an essentially normal amount and activity of D90A mutant CuZn-SOD in CNS tissues of ALS cases. The increased occurrence of N-terminally truncated mutant subunits may indicate a difference in degradation routes compared with the wild-type enzyme, resistance against subsequent proteolytic steps and/or a compromised downstream proteolytic machinery. Molecular fragments accumulated to a greater extent from the D90A mutant enzyme might contribute to the motor neurone degeneration. We also determined the other SOD isoenzymes: in the controls, CuZn-SOD contributed 75%, extracellular SOD 25% and Mn-SOD <5% of the total SOD activity. There was no difference in the amount of extracellular SOD between any of the groups.
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| 7. |
- Jonsson, Andreas P., et al.
(författare)
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Minute quantities of misfolded mutant superoxide dismutase-1 cause amyotrophic lateral sclerosis
- 2004
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 127:Pt 1, s. 73-88
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Tidskriftsartikel (refereegranskat)abstract
- Mutant forms of superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS) by an unknown noxious mechanism. Using an antibody against a novel epitope in the G127insTGGG mutation, mutant SOD1 was studied for the first time in spinal cord and brain of an ALS patient. The level was below 0.5% of the SOD1 level in controls. In corresponding transgenic mice the content of mutant SOD1 was also low, although it was enriched in spinal cord and brain compared with other tissues. In the mice the misfolded mutant SOD1 aggregated rapidly and 20% occurred in steady state as detergent-soluble protoaggregates. The misfolded SOD1 and the protoaggregates form, from birth until death, a potentially noxious burden that may induce the motor neuron injury. Detergent-resistant aggregates, as well as inclusions of mutant SOD1 in motor neurons and astrocytes, accumulated in spinal cord ventral horns of the patient and mice with terminal disease. The inclusions and aggregates may serve as terminal markers of long-term assault by misfolded SOD1 and protoaggregates.
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