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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
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
Cerebrovascular Disease Research Center, Departments of Neurology and Biomedical Engineering, University of Miami, Miami, FL 33101, USA.
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2001 (Engelska)Ingår i: Brain Research Protocols, ISSN 1385-299X, E-ISSN 1872-809X, Vol. 7, nr 1, s. 76-85Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2001. Vol. 7, nr 1, s. 76-85
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-133948DOI: 10.1016/S1385-299X(01)00046-0ISI: 000168088300010PubMedID: 11275527Scopus ID: 2-s2.0-0035080062OAI: oai:DiVA.org:umu-133948DiVA, id: diva2:1090134
Tillgänglig från: 2017-04-22 Skapad: 2017-04-22 Senast uppdaterad: 2019-03-19Bibliografiskt granskad
Ingår i avhandling
1. Apoptotic and necrotic cell death after photothrombotic ring stroke: characterization of a stroke model and its morphological and molecular consequences
Öppna denna publikation i ny flik eller fönster >>Apoptotic and necrotic cell death after photothrombotic ring stroke: characterization of a stroke model and its morphological and molecular consequences
2003 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Cerebral ischemic cell death is a major cause of disability and death among stroke patients. The brain cell demise can occur through apoptosis or necrosis or as a continuum of both. This study aimed at establishing a dual setup of a photothrombotic ring stroke model and exploring its morphological and molecular consequences.

    Photothrombotic ring stroke was induced in adult male Wistar rats by a ring shaped laser irradiation beam (514.5nm, outer diameter 5mm, thickness 0.35 mm) for 120 seconds focused on the exposed intact skull bone with simultaneous intravenous infusion of the photosensitizer erythrosin B (17 mg/kg). By using otherwise identical experimental conditions, high intensity irradiation (1.94 W/cm2) resulted in consistent lack of reperfusion in the region at risk whereas low intensity irradiation (0.90 W/cm2) induced late spontaneous reperfusion. The morphological appearance of apoptotic and necrotic cells was demonstrated by H&E, TUNEL and Hoechst stainings under light microscopy, immunohistochemistry and electron microscopy. This was further confirmed by gel electrophoresis showing DNA laddering that coexisted with DNA smear. Cell counts revealed that apoptotic cells appeared earlier (at 24 h) and remained as long as the necrotic cells, that is up to 72 hours after ischemic onset in regions with severe CBF reduction. After low intensity irradiation, we observed early and widespread increased expression of the anti-apoptotic protein bcl-w and a prolonged elevation of Bcl-2 with unchanged pro-apoptotic Bax in mitochondria. In contrast, decreased bcl-w and Bcl-2 with scattered Bax remained after high intensity irradiation. Correspondingly, the release of the pro-apoptotic factor Smac/DIABLO from the mitochondria to the cytosol was more persistent in high- compared with low-intensity irradiation.   

    Apoptotic and necrotic cell death coexisted in the same regions at the same time after photothrombotic ring stroke induced by low- or high-intensity irradiation, where spontaneous morphological recovery or pannecrosis were evident in the region at risk. The ratios between Bcl-w, Bcl-2 and Bax may direct the translocation of Smac/DIABLO from the mitochondria to the cytosol and thereby influence cell death or survival after focal cerebral ischemia.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2003. s. 59
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 826
Nationell ämneskategori
Medicin och hälsovetenskap Neurovetenskaper
Identifikatorer
urn:nbn:se:umu:diva-133950 (URN)91-7305-390-2 (ISBN)
Disputation
2003-02-28, Sal B, plan 9, By 1D, NUS, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2019-03-19 Skapad: 2017-04-22 Senast uppdaterad: 2019-03-21Bibliografiskt granskad

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