| 1. |
- Bendel, Olof, et al.
(författare)
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Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory
- 2005
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 25:12, s. 1586-1595
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Tidskriftsartikel (refereegranskat)abstract
- The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.
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| 2. |
- Bendel, Olof, et al.
(författare)
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Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension
- 2005
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1033:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40-45 mmHg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.
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| 3. |
- Bueters, Tjerk, et al.
(författare)
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Degeneration of newly formed CA1 neurons following global ischemia in the rat
- 2008
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Ingår i: Experimental Neurology. - New York, USA : Academic Press. - 0014-4886 .- 1090-2430. ; 209:1, s. 114-124
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Tidskriftsartikel (refereegranskat)abstract
- The pyramidal neurons of the hippocampal CA1 region are essential for spatial learning and memory and are almost entirely destroyed 7-14 days after transient cerebral ischemia (DAI). Recently, we found that CA1 neurons reappeared at 21-90 DAI, in association with a recovery of ischemia-induced deficits in spatial learning and memory. However, at 125 DAI the number of neurons was fewer than at 90 DAI, suggesting that the new nerve cells undergo neurodegeneration during this time period. We therefore investigated whether neuronal degeneration occurred between 90 and 250 DAI and how this related to learning and memory performance. We found that many of the new CA1 neurons previously seen at 90 DAI had disappeared at 250 DAI. In parallel, large mineralized calcium deposits appeared in the hippocampus and thalamus, in association with neuroinflammatory and astroglial reactions. In spite of the extensive CA1 damage, the ischemic rats showed no deficiencies in spatial learning and memory, as analyzed in the Morris water maze and a complimentary water maze test based on sequential left-right choices. However, ischemia rats showed a general increase in swim length in the Morris water maze suggesting altered search behaviour. Taken together, these results indicate that the CA1 neurons that reappear after transient global ischemia to a large extent degenerate at 125-250 DAI, in parallel with the appearance of a less efficient search strategy.
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| 4. |
- Hillefors, M., et al.
(författare)
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Prominent binding of the dopamine D3 agonist [3H]PD 128907 in the caudate-putamen of the adult rat
- 1999
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 822:1-2, s. 126-131
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Tidskriftsartikel (refereegranskat)abstract
- We have analyzed the binding properties of the selective D3 receptor agonist [3H]PD 128907 in 120 days old rats. In tissue sections, we found high numbers of binding sites for [3H]PD 128907 both in the islands of Calleja and the caudate-putamen (Bmax values being 500 and 1000 fmol/mg protein, respectively). The KD values were higher in the caudate-putamen than in the islands of Calleja. Similar regional differences in Bmax and KD values were observed in membranes from the caudate-putamen and the subcortical limbic region. The distribution of [3H]PD 128907 in adult rats is markedly different from that observed in young rats. Taken together, the present results suggest a prominent presence of D3 receptors in the caudate-putamen of adult, but not young, rats. Hence, these findings may have important physiological, pathophysiological, and clinical implications.
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| 5. |
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| 6. |
- von Euler, G., et al.
(författare)
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Coactivation of dopamine D1 and D2 receptors increases the affinity of cholecystokinin-8 receptors in membranes from post-mortem human caudate-putamen
- 1992
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Ingår i: Brain Research. - Amsterdam, Netherlands : Elsevier. - 0006-8993 .- 1872-6240. ; 584:1-2, s. 157-162
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Tidskriftsartikel (refereegranskat)abstract
- The effects of dopamine in vitro were investigated on the binding sites for cholecystokinin-8 (sulphated, CCK-8) and neurotensin in membrane preparations of the caudate-putamen and nucleus accumbens of post-mortem human brains. Dopamine reduced the IC50 value of competition curves with CCK-8 for [125I]CCK-8 binding in membranes from the caudate-putamen, but not the nucleus accumbens, with a maximal decrease of -25 +/- 9% at 300 nM of dopamine. This decrease could be antagonized by 100 nM of SCH 23390 or 100 nM of raclopride. Kinetic analysis of [125I]CCK-8 binding showed a decrease in the first order dissociation rate constant and in the kinetic Kd (-22 +/- 6% and -24 +/- 6%, respectively) at 300 nM of dopamine, without any significant effect on the apparent or actual association rate constant. Competition curves with neurotensin versus [125I]neurotensin were not affected by dopamine (10-1000 nM) in membranes from the caudate-putamen or the nucleus accumbens. These results suggest that dopamine, by synergistic stimulation of both D1 and D2 receptors, selectively increases the affinity of CCK-8 receptors in the human caudate-putamen, by a selective inhibition of ligand dissociation. This increase may reflect a positive feed-back mechanism, further enhancing the modulatory effects of CCK-8 on dopamine neurotransmission.
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| 7. |
- von Euler, Mia, 1967-, et al.
(författare)
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Inhalation of low concentrations of toluene induces persistent effects on a learning retention task, beam-walk performance, and cerebrocortical size in the rat
- 2000
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Ingår i: Experimental Neurology. - New York, USA : Academic Press. - 0014-4886 .- 1090-2430. ; 163:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The organic solvent toluene is widely used in industry. The threshold limit value for extended occupational exposure to toluene is presently set to 200 ppm in the United States. We have investigated the effect of an inhalation exposure of 80 ppm for 4 weeks (6 h/day, 5 days/week), followed by a postexposure period of at least 4 weeks, on behavior and brain features in the rat. Toluene exposure appeared to affect spatial memory, since toluene-exposed rats showed a longer time in the correct quadrant in a Morris swim maze. This effect may indicate that the exposed rats used their praxis strategy longer before they started to look for the platform elsewhere. Toluene-exposed rats showed trends for increases in both locomotion and rearing behaviors and a significantly reduced beam-walk performance. The area of the cerebral cortex, especially the parietal cortex, was decreased by 6-10% in toluene-exposed rats, as shown by magnetic resonance imaging of living rats and autoradiograms of frozen brain sections. The K(D) and B(max) values of the dopamine D(3) agonist [(3)H]PD 128907 were not affected by toluene, as measured in caudate-putamen and subcortical limbic area using biochemical receptor binding assays and in caudate-putamen and islands of Calleja using quantitative receptor autoradiography. Hence, previously demonstrated persistent effects by toluene on the binding characteristics of radioligands binding to both D(2) and D(3) receptors seem to indicate a persistent effect of toluene selectively on dopamine D(2) receptors. Taken together, the present results indicate that exposure to low concentrations of toluene leads to persistent effects on cognitive, neurological, and brain-structural properties in the rat.
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| 8. |
- von Euler, Mia, 1967-, et al.
(författare)
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Profound but transient deficits in learning and memory after global ischemia using a novel water maze test
- 2006
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Ingår i: Behavioural Brain Research. - Amsterdam, Netherlands : Elsevier. - 0166-4328 .- 1872-7549. ; 166:2, s. 204-10
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Tidskriftsartikel (refereegranskat)abstract
- The pyramidal CA1 neurons of the hippocampus are critically involved in spatial learning and memory. These neurons are especially vulnerable to cerebral ischemia, but in spite of this, it has been consistently difficult to show any learning and memory deficits in two-vessel occlusion models of global ischemia. Transient global ischemia was induced in adult male rats under general anaesthesia administered by artificial respiration to prevent respiratory arrest. Systemic blood pressure was reduced to below 50 mmHg by instant adjustments of the halothane concentration, before and during bilateral occlusion of the carotid arteries. Cerebral blood flow was monitored by laser-Doppler flowmetry. Dying neurons were detected by TUNEL at 14 days after ischemia and surviving neurons by NeuN at 14 and 125 days after ischemia. Learning and memory was assessed in a novel water maze with three successive left-right choices. Transient global ischemia produced a profound and selective degeneration of CA1 neurons at 14 days after ischemia. This degeneration was associated with severe impairments in learning at 13 days after ischemia and in memory, as tested 24 h afterwards. At 125 days after ischemia, there was no significant learning and memory impairment, whereas the number of CA1 neurons was increased. These results show that transient global ischemia induced by two-vessel occlusion may lead to severe, but transient, impairments in learning and memory using a novel water maze, and that restored learning and memory is associated with an increased number of CA1 neurons.
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| 9. |
- Berglund, Annika, et al.
(författare)
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Higher prehospital priority level of stroke improves thrombolysis frequency and time to stroke unit : the Hyper Acute STroke Alarm (HASTA) study
- 2012
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Ingår i: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 43:10, s. 2666-2670
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences.METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel.RESULTS: During 2008, 942 patients were randomized of which 53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in the Emergency Medical Communication Center randomized intervention group reached the stroke unit 26 minutes earlier than the control group (P<0.001) after the emergency call. Thrombolysis was given to 24% of the patients in the intervention group compared with 10% of the control subjects (P<0.001). The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention.CONCLUSIONS: This randomized study shows negligible harm to other medical emergencies, a significant increase in thrombolysis frequency, and a shorter time to the stroke unit for patients with stroke upgraded to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care.
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| 10. |
- Garcia-Ptacek, Sara, et al.
(författare)
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Prestroke Mobility and Dementia as Predictors of Stroke Outcomes in Patients Over 65 Years of Age : A Cohort Study From The Swedish Dementia and Stroke Registries
- 2018
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Ingår i: Journal of the American Medical Directors Association. - Hagerstown, Maryland : Lippincott Williams & Wilkins. - 1525-8610 .- 1538-9375. ; 19:2, s. 154-161
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore the association between prestroke mobility dependency and dementia on functioning and mortality outcomes after stroke in patients>65 years of age.DESIGN: Longitudinal cohort study based on SveDem, the Swedish Dementia Registry and Riksstroke, the Swedish Stroke Registry.PARTICIPANTS: A total of 1689 patients with dementia >65 years of age registered in SveDem and suffering a first stroke between 2007 and 2014 were matched with 7973 controls without dementia with stroke.MEASUREMENTS: Odds ratios (ORs) and 95% confidence intervals (CIs) for intrahospital mortality, and functioning and mortality outcomes at 3 months were calculated. Functioning included level of residential assistance (living at home without help, at home with help, or nursing home) and mobility dependency (independent, needing help to move outdoors, or needing help indoors and outdoors).RESULTS: Prestroke dependency in activities of daily living and mobility were worse in patients with dementia than controls without dementia. In unadjusted analyses, patients with dementia were more often discharged to nursing homes (51% vs 20%; P < .001). Mortality at 3 months was higher in patients with dementia (31% vs 23% P < .001) and fewer were living at home without help (21% vs 55%; P < .001). In adjusted analyses, prestroke dementia was associated with higher risk of 3-month mortality (OR 1.34; 95% CI 1.18-1.52), requiring a higher level of residential assistance (OR 4.07; 3.49-.75) and suffering from more dependency in relation to mobility (OR 2.57; 2.20-3.02). Patients with dementia who were independent for mobility prestroke were more likely to be discharged to a nursing home compared with patients without dementia with the same prestroke mobility (37% vs 16%; P < .001), but there were no differences in discharge to geriatric rehabilitation (19% for both; P = .976). Patients, who moved independently before stroke, were more often discharged home (60% vs 28%) and had lower mortality. In adjusted analyses, prestroke mobility limitations were associated with higher odds for poorer mobility, needing more residential assistance, and death.CONCLUSIONS: Patients with mobility impairments and/or dementia present a high burden of disability after a stroke. There is a need for research on stroke interventions among these populations.
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