scholarly journals Plasminogen Activation in Focal Cerebral Ischemia and Reperfusion

2000 ◽  
Vol 20 (2) ◽  
pp. 337-342 ◽  
Author(s):  
T. Pfefferkorn ◽  
B. Staufer ◽  
M. Liebetrau ◽  
G. Bültemeier ◽  
M. R. Vosko ◽  
...  

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2% ± 8.5% and 19.4% ± 30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8% ± 42.2%, P < 0.05) but not in the cortex (43.0% ± 34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury ( r = 0.873, P < 0.001). No such correlation was found in the cortex ( r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.

2017 ◽  
Vol 38 (8) ◽  
pp. 1371-1383 ◽  
Author(s):  
Chi-Hoon Choi ◽  
Kyung Sik Yi ◽  
Sang-Rae Lee ◽  
Youngjeon Lee ◽  
Chang-Yeop Jeon ◽  
...  

To assess hyperacute focal cerebral ischemia in rats on 3.0-Tesla diffusion-weighted imaging (DWI), we developed a novel voxel-wise lesion segmentation technique that overcomes intra- and inter-subject variation in apparent diffusion coefficient (ADC) distribution. Our novel technique involves the following: (1) intensity normalization including determination of the optimal type of region of interest (ROI) and its intra- and inter-subject validation, (2) verification of focal cerebral ischemic lesions at 1 h with gross and high-magnification light microscopy of hematoxylin-eosin (H&E) pathology, (3) voxel-wise segmentation on ADC with various thresholds, and (4) calculation of dice indices (DIs) to compare focal cerebral ischemic lesions at 1 h defined by ADC and matching H&E pathology. The best coefficient of variation was the mode of the left hemisphere after normalization using whole left hemispheric ROI, which showed lower intra- (2.54 ± 0.72%) and inter-subject (2.67 ± 0.70%) values than the original. Focal ischemic lesion at 1 h after middle cerebral artery occlusion (MCAO) was confirmed on both gross and microscopic H&E pathology. The 83 relative threshold of normalized ADC showed the highest mean DI (DI = 0.820 ± 0.075). We could evaluate hyperacute ischemic lesions at 1 h more reliably on 3-Tesla DWI in rat brains.


2018 ◽  
pp. 126-131

Ligadura de arteria carótida común y exsanguinación como modelo experimental de isquemia cerebral focal en ratas Ligation of common carotid artery and exsanguination as experimental model of focal cerebral ischemia in rats  Luz Marina Guerrero Espino Universidad Nacional de Trujillo, Calle Salaverry N⁰545-Trujillo, Perú DOI: https://doi.org/10.33017/RevECIPeru2013.0017/ Resumen La isquemia cerebral   es el proceso fisiopatológico caracterizado por la disfunción de una porción del tejido cerebral secundario a la disminución del flujo en una arteria cerebral concreta.  La mejor herramienta que se dispone hoy para el estudio de la fisiopatología de la isquemia cerebral son los modelos experimentales, que permiten abordar de manera simple el cuidado de esta afección que se caracteriza por su complejidad y heterogeneidad. Considerando que  las investigaciones sobre este campo es ilimitada, no solo por la trascendencia sino por el costo social de la enfermedad  ,el estudio de nuevas metodologías experimentales permitirán alcanzar mejores herramientas con rigor científico para el conocimiento fisiopatológico, terapéutico y preventivo de la enfermedad isquémica cerebral.Por lo que nos propusimos  determinar si la ligadura de arteria carótida común izquierda y exsanguinación     puede ser utilizada como modelo de isquemia cerebral focal en ratas. Se usaron 36 ratas, machos de 8 a 9 semanas de edad, con 200 ± 20gr de peso, que se mantuvieron en condiciones estándar de iluminación, ciclos diarios de 12 horas de luz y 12 de oscuridad, a una temperatura ambiente de 24-25°C, los especímenes fueron distribuidas en dos grupos: Grupo Sham o seudo operado y Grupo Experimental (operado). Se procedió a la sangría por punción cardiaca, y se extrajo de cada rata el 10% del volumen de sangre circulante. Bajo condiciones de asepsia y antisepsia, se realizó una incisión en la línea media del cuello y diseccionó la piel, tejido subcutáneo y músculo hasta lograr identificar la arteria carótida común (ACC) izquierda y se ligó con sutura Nylon 5-0 para interrumpir la circulación sanguínea de manera ipsilateral, se suturó la herida y se administró lidocaína, finalmente se dejó descansar al animal a una temperatura ligeramente mayor a la ambiental en cámaras previamente confeccionadas. Luego de 24 horas de aplicar la cirugía, se sacrificaron los especímenes por sobredosis de anestésico y se realizó la remoción del cerebro y el análisis histopatológico de secciones coronales en tres regiones neocortex, hipocampo y ganglios basales, por ser las áreas más vulnerables a daño en una lesión isquémica. Se encontró que las mayores características neuronales que indican daño celular se manifestaron en el Grupo Experimental con un p‹0.01 y la zona con mayor incidencia de daño es el ganglio basal, p ‹0.01. Se concluyó que la ligadura de arteria carótida común izquierda y ex sanguinación produce daños neuronales localizados y la zona más afectada es el ganglio basal. Descriptores:  isquemia cerebral focal, ligadura arteria carótida común ex sanguinación. Abstract Cerebral ischemia is the pathophysiological process characterized by dysfunction of a portion of brain tissue secondary to decreased flow in specific brain artery. The best tool available today to study the pathophysiology of cerebral ischemia are experimental models, which allow a simple way to address the care of the condition which is characterized by complexity and heterogeneity. Whereas research on this field is unlimited, not only because of the importance but by the social cost of the disease, the study of new experimental methodologies to achieve better tools for scientific rigor in pathophysiological knowledge, treatment and prevention of cerebral ischemic disease. So we set out to determine whether the common carotid artery ligation and ex sanguination left can be used as a model of focal cerebral ischemia in rats. We used 36 male rats of 8 to 9 weeks of age, with 200 ± 20g of weight, were maintained in standard lighting conditions, daily cycles of 12 hours of light and 12 of darkness were used at an ambient temperature of 24-25 ° C, the specimens were divided into two groups: Sham Groups and Experimental Group (operated). We proceeded to the bleeding via cardiac puncture, and extracted from each rat 10% of circulating blood volume. Under aseptic and antiseptic conditions, an incision was made in the midline of the neck and dissected the skin, subcutaneous tissue and muscle to be able to identify the left common carotid artery (CCA) and ligated with 5-0 nylon suture to interrupt circulation way of ipsilateral blood, the wound was sutured and received lidocaine finally allowed to rest the animal at a slightly higher environmental chambers previously made temperature. After 24 hours of surgery applied, the specimens were sacrificed by overdose of anesthetic and removal of the brain and histopathological analysis of coronal sections in three regions neocortex, hippocampus and basal ganglia was performed, being the most vulnerable areas to damage ischemic injury. It was found that the major characteristics that indicate neuronal cell damage demonstrated in the experimental group with p <0.01 and the area with the highest incidence of injury is the basal ganglia, p <0.01. It was concluded that ligation of left common carotid artery and ex sanguinación produces localized neuronal damage and the most affected area is the basal ganglia. Keywords: Focal cerebral ischemia, ligation of left common carotid artery and ex sanguination


2001 ◽  
Vol 21 (4) ◽  
pp. 430-439 ◽  
Author(s):  
Laszlo Olah ◽  
Stefan Wecker ◽  
Mathias Hoehn

Changes in apparent diffusion coefficients (ADC) were compared with alterations of adenosine triphosphate (ATP) concentration and pH in different phases of transient focal cerebral ischemia to study the ADC threshold for breakdown of energy metabolism and tissue acidosis during ischemia and reperfusion. Male Wistar rats underwent 1 hour of middle cerebral artery occlusion without recirculation (n = 3) or with 1 hour (n = 4) or 10 hours of reperfusion (n = 5) inside the magnet, using a remotely controlled thread occlusion model. ADC maps were calculated from diffusion-weighted images and normalized to the preischemic value to obtain relative ADC maps. Hemispheric lesion volume (HLV) was determined on the last relative ADC maps at different relative ADC thresholds and was compared to the HLV measured by ATP depletion and by tissue acidosis. The HLVs, defined by ATP depletion and tissue acidosis, were 26.0% ± 10.6% and 38.1% ± 6.5% at the end of ischemia, 3.3% ± 2.4% and 4.8% ± 3.5% after 1 hour of reperfusion, and 11.2% ± 4.7% and 10.9% ± 5.2% after 10 hours of recirculation, respectively. The relative ADC thresholds for energy failure were consistently approximately 77% of the control value in the three different groups. The threshold for tissue acidosis was higher at the end of ischemia (86% of control) but was similar to the results obtained for ATP depletion after 1 hour (78% of control) and 10 hours (76% of control) of recirculation. These results indicate that the described relative ADC threshold of approximately 77% of control provides a good estimate for the breakdown of energy metabolism not only during middle cerebral artery occlusion but also at the early phase of reperfusion, when recovery of energy metabolism is expected to occur, or some hours later, when development of secondary energy failure was described.


2004 ◽  
Vol 24 (6) ◽  
pp. 668-676 ◽  
Author(s):  
Hiroharu Kataoka ◽  
Seong-Woong Kim ◽  
Nikolaus Plesnila

The contribution of leukocyte infiltration to brain damage after permanent focal cerebral ischemia and the underlying molecular mechanisms are still unclear. Therefore, the aim of this study was to establish a mouse model for the visualization of leukocytes in the cerebral microcirculation in vivo and to investigate leukocyte-endothelial interaction (LEI) after permanent middle cerebral artery occlusion (MCAO). Sham-operated 129/Sv mice showed physiologic LEI in pial venules as observed by intravital fluorescent microscopy. Permanent focal cerebral ischemia induced a significant increase of LEI predominantly in pial venules. The number of rolling and adherent leukocytes reached 36.5 ± 13.2/100 μm × min and 22.5 ± 7.9/100 μm × min, respectively at 120 minutes after MCAO ( P = 0.016 vs. control). Of note, rolling and adherent leukocytes were also observed in arterioles of ischemic animals (7.3 ± 3.0/100 μm × min rolling and 3.0 ± 3.6/100 μm × min adherent). Capillary density was not different between groups. These results demonstrate that leukocytes accumulate in the brain not only after transient but also after permanent focal cerebral ischemia and may therefore contribute to brain damage after stroke without reperfusion.


1991 ◽  
Vol 260 (2) ◽  
pp. H563-H568 ◽  
Author(s):  
A. L. Betz ◽  
J. Randall ◽  
D. Martz

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.


2007 ◽  
Vol 28 (4) ◽  
pp. 812-823 ◽  
Author(s):  
Richard Milner ◽  
Stephanie Hung ◽  
Xiaoyun Wang ◽  
Maria Spatz ◽  
Gregory J del Zoppo

During focal cerebral ischemia, the detachment of astrocytes from the microvascular basal lamina is not completely explained by known integrin receptor expression changes. Here, the impact of experimental ischemia (oxygen—glucose deprivation (OGD)) on dystroglycan expression by murine endothelial cells and astrocytes grown on vascular matrix laminin, perlecan, or collagen and the impact of middle cerebral artery occlusion on αβ-dystroglycan within cerebral microvessels of the nonhuman primate were examined. Dystroglycan was expressed on all cerebral microvessels in cortical gray and white matter, and the striatum. Astrocyte adhesion to basal lamina proteins was managed in part by α-dystroglycan, while ischemia significantly reduced expression of dystroglycan both in vivo and in vitro. Furthermore, dystroglycan and integrin α6β4 expressions on astrocyte end-feet decreased in parallel both in vivo and in vitro. The rapid loss of astrocyte dystroglycan during OGD appears protease-dependent, involving an matrix metalloproteinase-like activity. This may explain the rapid detachment of astrocytes from the microvascular basal lamina during ischemic injury, which could contribute to significant changes in microvascular integrity.


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