| 1. |
- Gu, Weigang, et al.
(författare)
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Neurotransmitter synthesis in poststroke cortical neurogenesis in adult rats.
- 2010
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Ingår i: Stem cell research. - : Elsevier. - 1876-7753 .- 1873-5061. ; 4:2, s. 148-154
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Tidskriftsartikel (refereegranskat)abstract
- Neurogenesis occurs in the cerebral cortex of adult rats after focal cerebral ischemia. Whether or not the newborn neurons could synthesize neurotransmitters is unknown. To elucidate such a possibility, a photothrombotic ring stroke model with spontaneous reperfusion was induced in adult male Wistar rats. The DNA duplication marker BrdU was repeatedly injected, and the rats were sacrificed at various times after stroke. To detect BrdU nuclear incorporation and various neurotransmitters, brain sections were processed for single/double immunocytochemistry and single/double/triple immunofluorescence. Stereological cell counting was performed to assess the final cell populations. At 48 h, 5 days, 7 days, 30 days, 60 days and 90 days after stroke, numerous cells were BrdU-immunolabeled in the penumbral cortex. Some of these were doubly immunopositive to the cholinergic neuron-specific marker ChAT or GABAergic neuron-specific marker GAD. As analyzed by 3-D confocal microscopy, the neurotransmitters acetylcholine and GABA were colocalized with BrdU in the same cortical cells. In addition, GABA was colocalized with the neuron-specific marker Neu N in the BrdU triple-immunolabeled cortical cells. This study suggests that the newborn neurons are capable of synthesizing the neurotransmitters acetylcholine and GABA in the penumbral cortex, which is one of the fundamental requisites for these neurons to function in the poststroke recovery.
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| 2. |
- Engdahl, Johan, et al.
(författare)
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Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding : the AF SPICE protocol
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity.Methods and analysis: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥ 70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up.Ethics and dissemination: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. Trial registration number NCT05134454.
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| 3. |
- Gu, Weigang, et al.
(författare)
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Cell division in the cerebral cortex of adult rats after photothrombotic ring stroke.
- 2009
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Ingår i: Stem Cell Research. - : Elsevier. - 1876-7753 .- 1873-5061. ; 2:1, s. 68-77
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Tidskriftsartikel (refereegranskat)abstract
- Neurogenesis has been shown to occur in the cerebral cortex in adult rats after ischemic stroke. The origin of the newborn neurons is largely unknown. This study aimed to explore cell division in the poststroke penumbral cortex. Adult male Wistar rats were subjected to photothrombotic ring stroke. After repeated delivery of the DNA duplication marker BrdU, the animals were sacrificed at various times poststroke. BrdU was detected by immunohistochemistry/immunofluorescence labeling, as was the M-phase marker Phos H3 and the spindle components alpha-tubulin/gamma-tubulin. DNA damage was examined by TUNEL staining. Cell type was ascertained by double immunolabeling with the neuronal markers Map-2ab/beta-tubulin III and NeuN/Hu or the astrocyte marker GFAP. From 16h poststroke, BrdU-immunolabeled cells appeared in the penumbral cortex. From 24h, Phos H3 was colocalized with BrdU in the nuclei. Mitotic spindles immunolabeled by alpha-tubulin/gamma-tubulin appeared inside the cortical cells containing BrdU-immunopositive nuclei. Unexpectedly, the markers of neuronal differentiation, Map-2ab/beta-tubulin III/NeuN/Hu, were expressed in the Phos H3-immunolabeled cells, and NeuN was detected in some cells containing spindles. This study suggests that in response to a sublethal ischemic insult, endogenous cells with neuronal immunolabeling may duplicate their nuclear DNA and commit cell mitosis to generate daughter neurons in the penumbral cortex in adult rats.
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| 4. |
- Gu, Weigang
(författare)
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Neurotransmitter synthesis by newborn neurons in the penumbral cortex, one step forwards to functional neurogenesis in the poststroke adult brain
- 2013
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Ingår i: Brain Research Journal. - : Nova Science Publishers, Inc.. - 1935-2875. ; 6:2, s. 237-248
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Tidskriftsartikel (refereegranskat)abstract
- Stroke ranks as the #1 cause of handicapping humans in adult life. Up to date, there is no medication available to cure the post stroke neurological deficits. Fortunately, stroke patients usually experience spontaneous neurologic improvements at various degrees, which start days after a stroke and last up to 18 months. The pathophysiological mechanisms responsible for the post stroke spontaneous recovery are scarcely understood. Endogenous neurogenesis is one of the plausible pathways. In response to an acute ischemic insult, endogenous cells inside the cerebral cortex have been found to be able to divide at as early as 24-48 hours after ischemia to generate daughter neurons in the penumbral cortex, which gives rise to a quick in situ cortical neurogenesis. Meanwhile, the proliferation of neural stem cells in the subventricular zone is augmented after stroke. These stem cells, in addition to following a rostral migrating stream to their routine destination olfactory bulbs, as they usually do under physiological circumstances, start to migrate towards the infarct region. One week after stroke, they arrive at the periinfarct cortex where they differentiate into neurons, which contributes to a late phase cortical neurogenesis. Whether or not newborn neurons may function in the post stroke adult brains is a crucial issue in neurogenesis research. For the newborn neurons to function, one of the fundamental prerequisites is that they must be capable of synthesizing neurotransmitters. To specifically address this question, the biosynthesis of the excitatory neurotransmitter acetylcholine (Ach) and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is examined in adult rat brains after a photothrombotic cortical "ring" stroke with spontaneous reperfusion. To label the newborn brain cells, the DNA duplication marker 5-bromodeoxyuridine (BrdU) is repeatedly injected so that it becomes incorporated into the nuclear DNA while brain cells proliferate. Single/double/triple immunohistochemistry or immunofluorescence is performed to detect possible appearances of neurotransmitters, their synthesizing enzymes and the nuclear BrdU incorporation. As early as 48 hours after a stroke, the neurotransmitters Ach and GABA are detected inside the cytoplasm of the newborn neurons in the ischemic penumbral cortex. These cholinergic and GABAergic neurons survive up to 90 days in the post stroke cortex. In addition, choline acetyl transferase (ChAT) and glutamic acid decarboxylase (GAD), which are the substrate enzymes essential for the biosynthesis of Ach and GABA, are also identified in the BrdUimmunolabelled newborn neurons. As analysed by 3-D confocal microscopy, the neurotransmitters are colocalized with the neuron-specific marker NeuN in the same cells while they exhibit BrdU-immuno-labelling in their nuclei, which confirms their neuronal identity. These data suggest that the newborn neurons in the penumbral cerebral cortex are capable of synthesizing the neurotransmitter Ach and GABA, which makes one fundamental step forwards to a functional neurogenesis in the post stroke adult brains.
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| 5. |
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| 6. |
- Gu, Weigang, et al.
(författare)
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Trombektomi gav gott resultat vid basilaristrombos : Förlängt tidsfönster för ingreppet föreslås
- 2014
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Ingår i: Läkartidningen. - : Läkartidningen förlag AB. - 0023-7205 .- 1652-7518. ; 111:27-28, s. 1188-1190
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Tidskriftsartikel (refereegranskat)abstract
- Basilaristrombos är ett akut och livshotande tillstånd. Intravenös trombolys är förstahandsbehandling, men ibland kan det vara en fördel att kombinera eller ersätta behandlingen med trombektomi. Lyckade behandlingsresultat med trombektomi finns beskrivna ända upp till 12–24 timmar efter insjuknandet. I fallbeskrivningarna diskuteras basilaristrombos hos två patienter som insjuknat med oklar medvetandesänkning. DT-angiografi gav diagnosen, och trombektomi kunde utföras 10 respektive 13 timmar efter insjuknandet. Långtidsresultatet var gott. Slutsatsen är att DT alltid ska kompletteras med DT-angiografi vid utredning av en akut medvetandepåverkad patient. Trombektomi bör övervägas om basilaristrombos påvisas.
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| 7. |
- Hu, XiaoLei, et al.
(författare)
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A photothrombotic ring stroke model in rats with or without late spontaneous reperfusion in the region at risk
- 1999
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 849:1-2, s. 175-186
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed at developing a dual setup of the photothrombotic ring stroke model with or without late spontaneous reperfusion in the region at risk and to explore the morphological consequences. The exposed crania of adult male Wistar rats were subjected to a ring-shaped laser-irradiation beam (o.d. 5.0 mm, 0.35 mm thick) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion. Transcardial carbon-black perfusion revealed that a laser intensity of 0.90 W/cm(2) resulted in late, that is, starting at 72 h, spontaneous reperfusion, whereas the lowest laser intensity that produced lack of reperfusion at 7 days post-irradiation was 1.84 W/cm(2). Laser-Doppler flowmetry showed prompt cortical cerebral blood flow (cCBF) reduction both in the ring lesion and region at risk (12% and 25% of control values) after high-intensity irradiation; these reduced flow values were more rapid and pronounced than in the low-intensity irradiation setup as previously shown. The high- compared with low-intensity irradiation setup produced more frequent occurrence of thrombi in the ring-lesion region and a larger ischemic cortical lesion with a more rapid pace of ischemic cellular changes in the ring-lesion region and the region at risk. The region at risk transformed into pannecrosis in the high-intensity, but recovered morphologically in the low-intensity irradiation setup. This dual photothrombotic setup with or without spontaneous reperfusion enables the study of events related to ischemic cell survival or death in an anatomically predefined region at risk.
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| 8. |
- Hu, Xiaolei, et al.
(författare)
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Progressive and reproducible focal cortical ischemia with or without late spontaneous reperfusion generated by a ring-shaped, laser-driven photothrombotic lesion in rats
- 2001
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Ingår i: Brain Research Protocols. - : Elsevier. - 1385-299X .- 1872-809X. ; 7:1, s. 76-85
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Tidskriftsartikel (refereegranskat)abstract
- Clinical stroke is mostly of thromboembolic origin, in which the magnitude of brain damage resulting from arterial occlusions depends on the degree and duration of the concomitant ischemia. To facilitate more controllable and reproducible study of stroke-related pathophysiological mechanisms, a photothrombotic ring stroke model was initially developed in adult rats. The ring interior zone comprises an anatomically well confined cortical region-at-risk which is gradually encroached by progressive hypoperfusion, thus mimicking the situation (albeit in inverse fashion) of an ischemic penumbra or stroke-in-evolution. Modification of this model using a thinner ring irradiation beam resulted in late spontaneous reperfusion in the cortical region-at-risk and a remarkable morphological tissue recovery in this ostensibly critically injured region. On the other hand, doubling the thin irradiating beam intensity facilitates a complementary situation in which lack of reperfusion in the region-at-risk after stroke induction leads to tissue pannecrosis. The dual photothrombotic ring stroke model, effectuated either with or without reperfusion and thereby tissue recovery or pannecrosis, may be well suited for the study of events related to postischemic survival or cell death in the penumbra region. To popularize the photothrombotic ring stroke model, we present a detailed protocol of how this model is induced in either version as well as protocols for transcardial carbon black perfusion and laser-Doppler flowmetry experiments.
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