In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon.

Sette, Giuliano; Baron, J. C.; Young, Alan R.; Miyazawa, Hidemitsu; Tillet, I; Barré, Louisa; Travère, J.-M.; Derlon, Jean-Michel; MacKenzie, Eric T.

doi:10.1161/01.str.24.12.2046

Cited by 142 publications

(105 citation statements)

References 37 publications

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“…5,13,16,17 Therefore, the delayed ischemic change of hyperintensity/relative hypointensity on T1W/T2W MRI in our patients could involve biochemical changes that shorten the T1 and T2 relaxation times. These biochemical factors include paramagnetic compounds 18 such as iron and manganese ions, and free radicals produced by macrophages.…”

Section: Discussion Delayed Ischemic Hyperintensity On T1w Mri After Ssdmentioning

confidence: 88%

Delayed Ischemic Hyperintensity on T1-Weighted MRI in the Caudoputamen and Cerebral Cortex of Humans After Spectacular Shrinking Deficit

Fujioka

Taoka

Hiramatsu

et al. 1999

Stroke

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Background and Purpose-Transient internal carotid artery (ICA)-middle cerebral artery (MCA) occlusion caused by cardiogenic embolus can lead to spectacular shrinking deficit (SSD): sudden hemispheric stroke syndrome followed by rapid improvement. The aim of this study was to investigate sequential neuroradiological changes in the brains of patients after SSD compared with those after brief cardiac arrest and hypoglycemia, which we previously studied with the same methods. Methods-We serially studied CT scans and MR images obtained at 1.5 T in 4 patients with SSD. All 4 patients suffered from transient neurological deficits due to cardiogenic embolus in ICA-MCA. The symptoms began to disappear from 25 to 50 minutes after onset. Results-Repeated CT scans demonstrated no abnormal findings in the affected cerebral hemisphere in 3 of the 4 patients and a small cortical infarct in the remaining 1. In each patient, repeated MRI between day 7 and month 23 after stroke showed basal ganglionic and cortical lesions. These lesions were hyperintense on T1-weighted and relatively hypointense on T2-weighted imaging. These ischemic lesions of hyperintensity on T1-weighted MRI subsided with time. Conclusions-Transient ICA-MCA occlusion leading to SSD produces a specific ischemic change with delayed onset in the basal ganglia and cerebral cortex in humans on MRI but not CT scans. We speculate that the lesions represent incomplete ischemic injury, including selective neuronal death, proliferation of glial cells, paramagnetic substance deposition, and/or lipid accumulation. Unlike brief cardiac arrest or hypoglycemia, the localized lesions on MRI of patients after SSD seem to be incomplete and to differ from infarction or hemorrhage. (Stroke. 1999;30:1038 -1042.)Key Words: carotid arteries Ⅲ cerebral ischemia, transient Ⅲ magnetic resonance imaging Ⅲ neuronal death T ransient internal carotid artery (ICA)-middle cerebral artery (MCA) occlusion due to cardiogenic embolus can lead to spectacular shrinking deficit (SSD) in patients with various heart diseases. 1 SSD refers to a sudden major hemispheric stroke syndrome followed by rapid improvement within a few hours after stroke, leaving mild or no deficits. Experimentally, 2,3 brief MCA occlusion (MCAO) causes selective neuronal necrosis and apoptosis with intact glial cells and microvessels in the caudoputamen and cerebral cortex. In these ischemic lesions, the brain tissue framework is preserved and no cavitation develops. This ischemic lesion with selective neuronal death and gliosis has been termed "incomplete infarction." 4 -6 Nakano et al 7 reported that selective neuronal damage slowly progressed in the dorsolateral striatum of rats for 4 weeks after 15 minutes' MCAO and that microvacuolation never occurred in the ischemic area. However, very few reports are available on the serial changes in the human brain after transient hemispheric ischemia leading to SSD, which represent the clinical equivalent of the experimental conditions described above.In humans, we previously invest...

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Section: Discussion Delayed Ischemic Hyperintensity On T1w Mri After Ssdmentioning

confidence: 88%

Delayed Ischemic Hyperintensity on T1-Weighted MRI in the Caudoputamen and Cerebral Cortex of Humans After Spectacular Shrinking Deficit

Fujioka

Taoka

Hiramatsu

et al. 1999

Stroke

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“…29,37,38 However, since the CBR is exclusively located in the cortex, not in the white matter and basal ganglia, 11 C-FMZ can detect the neuronal damage in the cortex. In contrast, 18 F-BCPP-EF can image to detect the neuronal damage in whole brain.…”

Section: Discussionmentioning

confidence: 99%

PET Imaging of Ischemia-Induced Impairment of Mitochondrial Complex I Function in Monkey Brain

Tsukada

Ohba

Nishiyama

et al. 2014

J Cereb Blood Flow Metab

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To assess the capability of 18 F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ( 18 F-BCPP-EF), a novel positron emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, as a specific marker of ischemia-induced neuronal death without being disturbed by inflammation, translational research was conducted using an animal PET in ischemic brains of Cynomolgus monkeys (Macaca fascicularis). Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hours, then PET scans were conducted at Day-7 with 15 O-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolism of oxygen (rCMRO 2 ), and 18 F-BCPP-EF for MC-I with arterial blood sampling. On Day-8, the additional PET scans conducted with 11 C-flumazenil ( 11 C-FMZ) for central-type benzodiazepine receptors, 11 C-PBR28 for translocator protein, and 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) for regional cerebral metabolic rate of glucose (rCMRglc). The total distribution volume (V T ) values of 18 F-BCPP-EF showed the significant reduction in MC-I activity in the damaged area at Day-7. When correlated with rCBF and rCMRO 2 , the V T values of 18 F-BCPP-EF provided better correlation with rCMRO 2 than with rCBF. In the inflammatory regions (region of interest, ROI PBR ) of the ischemic hemisphere detected with 11 C-PBR28, higher 18 F-FDG uptake and lower V T of 18 F-BCPP-EF, 11 C-FMZ, and rCMRO 2 than those in normal contralateral hemisphere were observed. These results strongly suggested that 18 F-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where 18 F-FDG could not owing to its high uptake into the activated microglia.

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“…Nonhuman primate (NHP) models offer an assessment of complex physiological, immunologic, biochemical, and behavioral outcomes most similar to those of humans. [14][15][16][17][18][19][20][21][22][23][24] These outcome measures complement those from other animal models by improving our understanding…”

mentioning

confidence: 99%

Impaired Arm Function and Finger Dexterity in a Nonhuman Primate Model of Stroke

McEntire

Choudhury

Torres

et al. 2016

Stroke

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The World Health Organization reports that stroke claims 6.2 million lives each year. There are ≈5.4 million stroke survivors with ≈80% requiring hand therapy. 1 The estimated economic burden for stroke exceeds $56.8 billion per year in the United States alone.Acute thrombolysis has a significant impact on the management of stroke, 2,3 with a therapeutic window that may extend ≤6 hours with intra-arterial delivery. 4 Yet only a minority of stroke victims benefit, and the majority experience progression of ischemia associated with neurological disabilities.Animal models that recapitulate human disabilities and disease pathology remain an unmet need in stroke research. There has been a tremendous advance in developing rodent experimental model stroke (reviewed in Durukan and Tatlisumak 5 and Carmichael 6 ). However, the lack of success in developing neuroprotective therapies in small animal models for stroke 7,8 prompted recommendations for additional research and development in large animal models with physiological, structural, and functional traits closer to those of humans before clinical trials.9,10 There has been a concerted effort in developing relevant large animal models. 11,12 Interspecies comparison suggests that cerebral venous angioarchitecture in large animals is closer to that of humans 13 ; nevertheless, such models remain relatively underdeveloped. Nonhuman primate (NHP) models offer an assessment of complex physiological, immunologic, biochemical, and behavioral outcomes most similar to those of humans.14-24 These outcome measures complement those from other animal models by improving our understanding Background and Purpose-Ischemic stroke is the leading cause of upper extremity motor impairments. Although several well-characterized experimental stroke models exist, modeling of upper extremity motor impairments, which are unique to primates, is not well established. Cortical representation of dexterous movements in nonhuman primates is functionally and topographically similar to that in humans. In this study, we characterize the African green monkey model of focal ischemia reperfusion with a defined syndrome, impaired dexterous movements. Methods-Cerebral ischemia was induced by transient occlusion of the M3 segment of the left middle cerebral artery.Motor and cognitive functions after stroke were evaluated using the object retrieval task with barrier-detour. Postmortem magnetic resonance imaging and histopathology were performed to map and characterize the infarct. Results-The middle cerebral artery occlusion consistently produced a necrotic infarct localized in the sensorimotor cortex in the middle cerebral artery territory. The infarction was reproducible and resulted in significant loss of fine motor function characterized by impaired dexterity. No significant cognitive impairment was detected. Magnetic resonance imaging and histopathology demonstrated consistent and significant loss of tissue on the left parietal cortex by the central sulcus covering the sensorimotor area. The results sug...

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In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon.

Cited by 142 publications

References 37 publications

Delayed Ischemic Hyperintensity on T1-Weighted MRI in the Caudoputamen and Cerebral Cortex of Humans After Spectacular Shrinking Deficit

Delayed Ischemic Hyperintensity on T1-Weighted MRI in the Caudoputamen and Cerebral Cortex of Humans After Spectacular Shrinking Deficit

PET Imaging of Ischemia-Induced Impairment of Mitochondrial Complex I Function in Monkey Brain

Impaired Arm Function and Finger Dexterity in a Nonhuman Primate Model of Stroke

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