scholarly journals Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Yoon Bum Lee ◽  
Seung Kuk Bae ◽  
Sung Suk Oh ◽  
Jong-ryul Choi

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

2018 ◽  
Vol 10 (1) ◽  
pp. 91-103 ◽  
Author(s):  
Bo Chen ◽  
Gandi Ng ◽  
Yahui Gao ◽  
See Wee Low ◽  
Edwin Sandanaraj ◽  
...  

Abstract The transient receptor potential melastatin 4 (TRPM4) channel has been suggested to play a key role in the treatment of ischemic stroke. However, in vivo evaluation of TRPM4 channel, in particular by direct channel suppression, is lacking. In this study, we used multimodal imaging to assess edema formation and quantify the amount of metabolically functional brain salvaged after a rat model of stroke reperfusion. TRPM4 upregulation in endothelium emerges as early as 2 h post-stroke induction. Expression of TRPM4 channel was suppressed directly in vivo by treatment with siRNA; scrambled siRNA was used as a control. T2-weighted MRI suggests that TRPM4 inhibition successfully reduces edema by 30% and concomitantly salvages functionally active brain, measured by 18F-FDG-PET. These in vivo imaging results correlate well with post-mortem 2,3,5-triphenyltetrazolium chloride (TTC) staining which exhibits a 34.9% reduction in infarct volume after siRNA treatment. Furthermore, in a permanent stroke model, large areas of brain tissue displayed both edema and significant reductions in metabolic activity which was not shown in transient models with or without TRPM4 inhibition, indicating that tissue salvaged by TRPM4 inhibition during stroke reperfusion may survive. Evans Blue extravasation and hemoglobin quantification in the ipsilateral hemisphere were greatly reduced, suggesting that TRPM4 inhibition can improve BBB integrity after ischemic stroke reperfusion. Our results support the use of TRPM4 blocker for early stroke reperfusion.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Meijuan Zhang ◽  
Mingxu Xia ◽  
Qiuchen Zhao ◽  
Yun Xu

Background: Inflammasome in microglia are critical to elicit inflammatory cascades in ischemic stroke. Histone deacetylases 3 (HDAC3) regulate acetylation states of histone and non-histone proteins and could be a powerful regulator of inflammatory process in stroke. Methods: Primary microglia, BV2 cells subjected to oxygen glucose deprivation (OGD) or LPS stimulation were applied to mimic inflammatory response in vitro . Middle cerebral artery occlusion (MCAO) model were applied to mimic acute stroke in vivo . Ischemic infarct volume and neurological functions were evaluated through 2,3,5-triphenyltetrazolium chloride (TTC) staining and Neurological Severity Scores (NSS) respectively. Expression of HDAC3, AIM2 inflammasome were detected by western blotting, PCR. Immunofluorescence was used to detect M1/M2 polarization. Luciferase activity of absent in melanoma 2 (AIM2) reporter promoter constructs was measured by fluorospectrophotometer. AIM2 knockdown and over-expression leti-virus were constructed to decrease or increase AIM2 expression. HDAC3 inhibitor RGFP966 was used to inhibit acetylation activity of HDAC3. Results: HDAC3 is widely distributed in cerebral cortex, lateral ventricular , hippocampus, cerebellar cortex ; HDAC3 and AIM2 expression were enhanced in LPS stimulated-microglia and MCAO model. A marked stimulatory effect of RGFP966 on H3K9Ac was observed in nuclear extracts form BV2 cells at the dosage of 15 uM. Treatment of RGFP966 increased both IL-4-stimulated expression of Ym-1 and CD206 at 4 h, 10 h, 24 h, 48 h. AIM2, NLRP-1 and NLRP3 significantly increased in MCAO+Vehicle group compared to sham group, but decreased in MCAO+RGFP966 group. RGFP966 inhibited the elevation of circulatory IL-18 and IL-1β induced by stroke. RGFP966 decreased infracted size and alleviated neurological deficit. Conclusions: HDAC3i alleviated ischemic stroke injury through modulating AIM2 inflammasome and microglia polarization. Selective HDAC3 inhibitor-RGFP966 could be a potential medication for combating ischemic brain injury.


2004 ◽  
Vol 100 (3) ◽  
pp. 498-504 ◽  
Author(s):  
Joachim Oertel ◽  
Michael Robert Gaab ◽  
Dirk-Thomas Pillich ◽  
Henry W. S. Schroeder ◽  
Rolf Warzok ◽  
...  

Object. The waterjet method of dissection has been shown to enable the precise dissection of the parenchyma vessels while preserving blood in cadaveric pig brains. The waterjet device has also been applied clinically to treat various diseases and disorders without complications. Evidence still remains to be gathered as to how the instrument performs in reducing surgical trauma, intraoperative blood loss, and postsurgical brain edema. In the present study the authors investigate these parameters in a comparison between waterjet dissection and ultrasonic aspiration in the rabbit brain in vivo. Methods. Thirty-one rabbits received identical bilateral frontal corticotomies, which were created using the waterjet device or an ultrasonic aspirator. The animals were killed 1, 3, or 7 days, or 6 weeks after surgery and their brains were processed for immunohistological analysis. Blood vessel preservation, intraoperative hemorrhage, postsurgical brain edema, and posttraumatic microglial and astoglial reactions were evaluated. Only in animals subjected to waterjet dissection were preserved vessels observed within the corticotomies. In addition, less intraoperative bleeding occurred in animals in which the waterjet was used. The microglial reaction was significantly reduced by waterjet dissection compared with ultrasonic aspiration; however, no difference in edema formation or astrocytic reactivity was observed. Conclusions. These results demonstrate that waterjet dissection appears to be less traumatic than ultrasonic aspiration with respect to intraoperative hemorrhage and postoperative microglial reactivity in the rabbit model. Nevertheless, no difference in edema formation could be demonstrated. It remains to be proven that the observed differences are of clinical relevance.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Aigul Saitgareyeva ◽  
Leyla Akhmadeyeva

The objective of our study was to evaluate the cerebroprotective effect of xanthohumol (ХN) on experimental models of acute ischemic stroke in vivo and in vitro. Materials and methods. We used middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) as in vivo and in vitro models. Our study subjects were Sprague-Dawley rats, which were randomly assigned to three groups: the control group and two MCAO groups with and without XN. The primary culture of cortical neurons was obtained from newborn rats. We employed the Bederson test and the corner test to evaluate neurological disorders. Results. The preliminary results indicated a possible cerebroprotective effect of XN in an ischemic stroke model. Conclusion. Preventive administration of XN before cerebral ischemia in an experiment can effectively reduce the volume of cerebral infarction and improve neurologic deficit 24 hours after MCAO.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P96-P97
Author(s):  
Lesley C. French ◽  
Tsunehisa Ohno ◽  
Majdani Omid ◽  
David L Zealear ◽  
Robert F Labadie ◽  
...  

Problem The midbrain periaqueductal gray (PAG) serves as a phonation integration center, coordinating respiratory, laryngeal, and orofacial activity during vocalization. The objective of this pilot study was to explore electrical excitation of the midbrain PAG for eliciting vocalization using an in-vivo rabbit preparation and determine the feasibility of using image guidance for improved localization of target midbrain structures. Methods Pilot experiments were conducted using four New Zealand White (NZW) breeder rabbits. In the first experiment, a stereotaxic frame was used to guide stimulation of the midbrain PAG without the use of image guidance. Decisions regarding track placements were directed by a stereotaxic atlas of the NZW rabbit brain. Histologic stains of axial brain sections were then obtained to determine electrode track positioning. In a subsequent experiment, magnetic resonance imaging (MRI) and computed tomography (CT) scans were obtained and used to localize midbrain structures for advanced planning capabilities. Results Without the use of image guidance, phonation was feasible, measuring 80–100 Hz using electrical excitation of the midbrain PAG (0.5 to 1.5 mA, 200 Hz, 2 second train duration). However, precise localization of the midbrain PAG proved technically challenging. Using CT and MRI data, scans could be loaded onto an image guided surgical system and combined using an image fusion tool for advanced planning. Conclusion The authors demonstrate the feasibility of electrical excitation of the midbrain PAG to produce vocalization in rabbits using a stereotaxic brain atlas and offer an alternative approach using image guidance for advanced planning and more precise localization of target midbrain structures. Significance The biomechanical forces of phonation and dynamic nature of vocal fold remodeling have created a need for chronic animal preparations to investigate these reparative processes in-vivo. Image guided techniques may improve the feasibility of brain stimulation techniques for eliciting and studying time dependent changes in vocal fold remodeling. Support NIH-NIDCD R03 DC008400.


2020 ◽  
Author(s):  
Alejandro Espinosa ◽  
Gabriela Meneses ◽  
Anahí Chavarría ◽  
Raúl Mancilla ◽  
José Pedraza-Chaverri ◽  
...  

1982 ◽  
Vol 47 (03) ◽  
pp. 269-274 ◽  
Author(s):  
R A G Smith ◽  
R J Dupe ◽  
P D English ◽  
J Green

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.


PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0236348
Author(s):  
Naila Cannes do Nascimento ◽  
Andrea P. dos Santos ◽  
M. Preeti Sivasankar ◽  
Abigail Cox
Keyword(s):  

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