| 51. |
- Gisselsson, Lennart, et al.
(författare)
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Actin redistribution underlies the sparing effect of mild hypothermia on dendritic spine morphology after in vitro ischemia.
- 2005
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 25:10, s. 1346-1355
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Tidskriftsartikel (refereegranskat)abstract
- Brain hypothermia is at present the most effective neuroprotective treatment against brain ischemia in man. Ischemia induces a redistribution of proteins involved in synaptic functions, which is markedly diminished by therapeutic hypothermia (33 degrees C). Dendritic spines at excitatory synapses are motile and show both shape changes and rearrangement of synaptic proteins as a consequence of neuronal activity. We investigated the effect of reduced temperature (33 degrees C and 27 degrees C compared with 37 degrees C), on spine motility, length and morphology by studying the distribution of GFP-actin before, during and after induction of in vitro ischemia. Because high-concentration actin filaments are located inside spines, dissociated hippocampal neurons (7-11 DIV) from transgenic mice expressing GFP-actin were used in this study. The movement of the spines and the distribution of GFP-actin were recorded using time-lapse fluorescence microscopy. Under normal conditions rapid rearrangement of GFP-actin was seen in dendritic spines, indicating highly motile spines at 37 degrees C. Decreasing the incubation temperature to 33 degrees C or 27 degrees C, dramatically reduces actin dynamics (spine motility) by approximately 50% and 70%, respectively. In addition, the length of the spine shaft was reduced by 20%. We propose that decreasing the temperature from 37 degrees C to 33 degrees C during ischemia decreases the neuronal actin polymerization rate, which reduces spine calcium kinetics, disrupts detrimental cell signaling and protects neurons against damage.
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| 52. |
- Golla, Sandeep S V, et al.
(författare)
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Quantification of [18F]DPA-714 binding in the human brain : initial studies in healthy controls and Alzheimer's disease patients
- 2015
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 35:5, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([(18)F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [(18)F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250 ± 10 MBq [(18)F]DPA-714. The model that provided the best fits to tissue time activity curves (TACs) was selected based on Akaike Information Criterion and F-test. The reversible two tissue compartment plasma input model with blood volume parameter was the preferred model for quantification of [(18)F]DPA-714 kinetics, irrespective of scan duration, volume of interest, and underlying volume of distribution (VT). Simplified reference tissue model (SRTM)-derived binding potential (BPND) using cerebellar gray matter as reference tissue correlated well with plasma input-based distribution volume ratio (DVR). These data suggest that [(18)F]DPA-714 cannot be used for separating individual AD patients from healthy subjects, but further studies including TSPO binding status are needed to substantiate these findings.
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| 53. |
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| 54. |
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| 55. |
- Grøgaard, B, et al.
(författare)
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Delayed hypoperfusion after incomplete forebrain ischemia in the rat. The role of polymorphonuclear leukocytes.
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 9:4, s. 500-5
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Tidskriftsartikel (refereegranskat)abstract
- The role of polymorphonuclear leukocytes (PMNLs) in postischemic delayed hypoperfusion in the rat brain was investigated. Cerebral ischemia was accomplished by reversible bilateral occlusion of the common carotid arteries for 15 min combined with bleeding to an MABP of 50 mm Hg. The animals of one group were depleted of their circulating. PMNLs by intraperitoneal injections of an antineutrophil serum (ANS) prior to the experiment. All animals included in this group had fewer than 0.2 x 10(9) circulating PMNLs/L at the start of the experiments. In another group ANS was injected intravenously for 5 min starting 2 min after the ischemic insult. After 4 min of recirculation, the number of circulating PMNLs in this group was below 10% of the normal. Control animals were injected with the same amount of normal sheep serum or were not treated at all. Sixty minutes after termination of ischemia, the local blood flow in previously ischemic cerebral structures was 40-50% of the normal as measured with the [14C]iodoantipyrine technique. In animals treated with ANS prior to the ischemic insult, the postischemic blood flow in the frontal, sensorimotor, and parietal cortex as well as caudoputamen and thalamus was significantly higher than that in non-ANS-treated animals. Treatment with ANS immediately after the ischemic period caused no improvement of the local CBF. It is concluded that PMNLs are involved in the cerebral postischemic flow derangements seen in this model. Their effects seem to be exerted during ischemia or immediately upon reinstitution of blood flow.
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| 56. |
- Guo, S. Z., et al.
(författare)
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Comparative transcriptome of neurons after oxygen-glucose deprivation: Potential differences in neuroprotection versus reperfusion
- 2018
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 38:12, s. 2236-2250
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Tidskriftsartikel (refereegranskat)abstract
- In the context of ischemic stroke, rescuing neurons can be theoretically achieved with either reperfusion or neuroprotection. Reperfusion works via the rapid restoration of oxygen and glucose delivery. Neuroprotection comprises molecular strategies that seek to block excitotoxicity, oxidative stress or various cell death pathways. Here, we propose the hypothesis that neurons rescued with reperfusion are different from neurons rescued with molecular neuroprotection. Neurons were subjected to oxygen-glucose deprivation (OGD) and then treated with "in vitro reperfusion" (i.e. energetic rescue via restoration of oxygen and glucose) or Z-VADfmk (to block apoptosis) or MK-801 (to block excitotoxicity). Levels of injury were titrated so that equivalent levels of neuronal salvage were achieved with reperfusion or neuroprotection. Gene arrays showed that OGD significantly altered the transcriptomic profiles of surviving neurons. Pathway analysis confirmed that a large spectrum of metabolic, inflammation, and signaling genes were perturbed. In spite of the fact that equal levels of neuronal salvage were achieved, energetic rescue renormalized the transcriptomic profiles in surviving neurons to a larger degree compared to neuroprotection with either Z-VADfmk or MK-801. These findings suggest that upstream reperfusion may bring salvaged neurons back "closer to normal" compared to downstream molecular neuroprotection.
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| 57. |
- Gustafson, I., et al.
(författare)
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Postischemic administration of idazoxan, an α-2 adrenergic receptor antagonist, decreases neuronal damage in the rat brain
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 9:2, s. 171-174
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Tidskriftsartikel (refereegranskat)abstract
- The effect of an α-2 receptor antagonist, idazoxan, on ischemic neuronal damage in the hippocampus and neocortex was studied in rats following 10 min of forebrain ischemia. Idazoxan was given 0.1 mg/kg i.v. immediately after recirculation, followed by 48 h of continuous infusion at a rate of 10 μg/kg/min. A histopathological examination of the CA1 region of the dorsal hippocampus and neocortex from each hemisphere was made on paraffin-embedded sections following 7 days of survival. In ischemic animals receiving an infusion of saline, 71% of the neurons in the hippocampal CA1 region were degenerated. In contrast, in the idazoxan-treated animals only 31% of the neurons were irreversibly damaged (p < 0.01). We conclude that postischemic administration of the α-2 antagonist idazoxan protects neurons against damage following cerebral ischemia. Rapid postischemic administration of α-2 adrenergic receptor antagonists could be an effective treatment after stroke and cardiac arrest.
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| 58. |
- Gustafson, Ingvar, et al.
(författare)
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Protection against ischemia-induced neuronal damage by the α2-adrenoceptor antagonist idazoxan : influence of time of administration and possible mechanisms of action
- 1990
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 10:6, s. 885-894
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Tidskriftsartikel (refereegranskat)abstract
- The protective effect of the α2-receptor antagonist idazoxan against neuronal damage in the neocortex and in the hippocampal CA1 region was studied in rats exposed to 10 min of incomplete forebrain ischemia. When administered i.v. immediately after ischemia (0.1 mg/kg) and subsequently for 6 h (10 μg/kg/min), idazoxan significantly reduced neuronal damage in the hippocampus (from 84 to 26%) and in the vulnerable parts of the neocortex (from 15 to 1%). The bolus dose alone provided no significant protection. When idazoxan administration was delayed for 30 min, no significant protection was noticed in the neocortex, and the effect in the hippocampus was ambiguous. A transient elevation of plasma corticosterone levels was induced during ischemia. Idazoxan administration for 2 h did not affect postischemic changes in corticosterone levels compared with saline infusion. Idazoxan (10-7-10-4 M) did not influence the in vitro binding to glutamate receptors in brain slices. Thus, the protective effect of idazoxan cannot be explained by suppression of the plasma corticosteroid levels or via an antagonistic effect on glutamate receptors. Idazoxan apparently protects neurons when given during the first hours of postischemic reperfusion, while histopathological necrosis of neurons becomes visible 48-72 h after ischemia. Detrimental processes causing delayed neuronal death occur in the early postischemic phase and can be influenced by adrenoceptor ligands. Idazoxan may protect by several mechanisms but probably exerts its protective postischemic effect mainly through an increased noradrenergic neuronal activity and an elevation of extracellular noradrenaline (NA) levels in the brain. The favorable effects of NA may either be due to inhibition of excitotoxic neurotransmission or activation of survival-promoting and trophic processes.
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| 59. |
- Haast, Roy A.M., et al.
(författare)
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Sex differences in stroke
- 2012
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 32:12, s. 2100-2107
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment.
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| 60. |
- Hanell, A
(författare)
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Discovery reliability
- 2019
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 39:6, s. 1185-1187
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Tidskriftsartikel (refereegranskat)
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