A Reproducible Model of Middle Cerebral Artery Occlusion in Mice: Hemodynamic, Biochemical, and Magnetic Resonance Imaging

Hata, Ryuji; Mies, Günter; Wiessner, Christoph; Fritze, K.; Hesselbarth, Daniel; Brinker, Gerrit; Hossmann, Konstantin‐Alexander

doi:10.1097/00004647-199804000-00004

Cited by 259 publications

(186 citation statements)

References 41 publications

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“…The animals were anesthetized with an intraperitoneal injection of a ketamine (100 mg/mL)/xylazine (20 mg/kg) mixture (1:1) at a dose of 1 mL/kg. The intraluminal filament method (Hata et al, 1998) was used for MCAO. The middle cerebral artery was occluded for 60 mins and reperfusion was confirmed when pulsations were again observed in the internal carotid artery.…”

Section: Middle Cerebral Artery Occlusion and Reperfusionmentioning

confidence: 99%

“…The severity of neurologic deficits was evaluated 24 h after ischemic injury using a five-point deficit score (0 = normal motor function, 1 = flexion of torso and of contralateral forelimb on lifting of the animal by tail, 2 = circling to the contralateral side but normal posture at rest, 3 = leaning to contralateral side at rest, and 4 = no spontaneous motor activity) (Hata et al, 1998). A rotarod was used to evaluate the motor function 24 h after MCAO (Gupta et al, 2002).…”

Section: Neurologic Deficit Score and Rotarod Testmentioning

confidence: 99%

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Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Mao

Zhang

Tuma

et al. 2010

J Cereb Blood Flow Metab

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Stroke is the third leading cause of death in the USA. Antithrombotic therapy targeting platelet activation is one of the treatments for ischemic stroke. Here we investigate the role of one of the thrombin receptors, protease-activated receptor 4 (PAR4), in a mouse transient middle cerebral artery occlusion (MCAO) model. After a 60 min MCAO and 23 h reperfusion, leukocyte and platelet rolling and adhesion on cerebral venules, blood-brain barrier (BBB) permeability, and cerebral edema were compared in PAR4-deficient mice and wild-type mice. Cerebral infarction volume and neuronal death were also measured. PAR4À/À mice had more than an 80% reduction of infarct volume and significantly improved neurologic and motor function compared with wild-type mice after MCAO. Furthermore, deficiency of PAR4 significantly inhibits the rolling and adhesion of both platelets and leukocytes after MCAO. BBB disruption and cerebral edema were also attenuated in PAR4À/À mice compared with wild-type animals. The results of this investigation indicate that deficiency of PAR4 protects mice from cerebral ischemia/reperfusion (I/R) injury, partially through inhibition of platelet activation and attenuation of microvascular inflammation.

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Section: Middle Cerebral Artery Occlusion and Reperfusionmentioning

confidence: 99%

Section: Neurologic Deficit Score and Rotarod Testmentioning

confidence: 99%

Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Mao

Zhang

Tuma

et al. 2010

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…The severity of neurological deficits were evaluated 24 h after ischemic insult using a five-point deficit score (0 = normal motor function; 1 = flexion of torso and of contralateral forelimb on lifting of the animal by tail; 2 = circling to the contralateral side but normal posture at rest; 3 = leaning to contralateral side at rest; and 4 = no spontaneous motor activity) (Hata et al, 1998).…”

Section: Neurological Evaluationmentioning

confidence: 99%

Cannabinoid CB₂Receptor Activation Decreases Cerebral Infarction in a Mouse Focal Ischemia/Reperfusion Model

Zhang

Martin

Adler

et al. 2007

J Cereb Blood Flow Metab

161

152

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Cannabinoid CB 2 Receptor (CB 2 ) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB 2 agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB 2 agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB 2 agonists significantly decreased cerebral infarction (30%) and improved motor function (P < 0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P < 0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB 2 agonists administered either at 1 h before or after MCAO (P < 0.05). CB 2 activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.

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“…62,63 Many groups have used experimental MCA ligation combined with hypoxia in rats or mice as models for human stroke. 64 DWI sequences are especially powerful in detecting early ischemia, and many studies have used this resource in animal imaging, along with perfusion studies that are capable of visualizing the penumbra-the area at risk for infarction that potentially can be salvaged (FIG. 8).…”

Section: Figmentioning

confidence: 99%

Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals

et al. 2005

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Summary:Over the last two decades, microscopic resolution in vivo magnetic resonance imaging (MRI) techniques have been developed and extensively used in the study of animal models of human diseases. Standard MRI methods are frequently used in clinical studies and in the general clinical practice of human neurological diseases. This generates a need for similar studies in experimental animal research. Because small rodents are the most commonly used species as animal models of neurological diseases, the MRI techniques need to be able to provide microscopic resolution and high signal-to-noise ratio images in relatively short time. Small animal MRI systems use very high field-strength magnets, which results in higher signal to noise ratio; however, the contrast characteristics of live tissue are different at these field strengths. In addition to standard MRI techniques, several new applications have been implemented in experimental animals, including diffusion and perfusion studies, MR angiography, functional MRI studies, MRI tractography, proton and phosphorous spectroscopy, cellular and molecular imaging using novel contrast methods. Here we give an overview of how to establish a small animal imaging facility with the goal of CNS imaging. We describe the basic physical processes leading to MR signal generation, highlighting the differences between standard clinical MRI and small animal MRI. Finally, typical findings in the most common neurological disease categories and novel MRI/magnetic resonance spectroscopy methods used in their study are also described.

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A Reproducible Model of Middle Cerebral Artery Occlusion in Mice: Hemodynamic, Biochemical, and Magnetic Resonance Imaging

Cited by 259 publications

References 41 publications

Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Cannabinoid CB₂Receptor Activation Decreases Cerebral Infarction in a Mouse Focal Ischemia/Reperfusion Model

Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals

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A Reproducible Model of Middle Cerebral Artery Occlusion in Mice: Hemodynamic, Biochemical, and Magnetic Resonance Imaging

Cited by 259 publications

References 41 publications

Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Deficiency of PAR4 Attenuates Cerebral Ischemia/Reperfusion Injury in Mice

Cannabinoid CB2Receptor Activation Decreases Cerebral Infarction in a Mouse Focal Ischemia/Reperfusion Model

Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals

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Cannabinoid CB₂Receptor Activation Decreases Cerebral Infarction in a Mouse Focal Ischemia/Reperfusion Model