ABSTRACT
We describe the case of a 63-year-old woman who developed a coronavirus disease 2019-associated acute encephalopathy with perivascular gadolinium enhancement.
Subject(s)
COVID-19/complications , Posterior Leukoencephalopathy Syndrome/pathology , Posterior Leukoencephalopathy Syndrome/virology , Contrast Media , Female , Gadolinium , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , SARS-CoV-2ABSTRACT
BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients. METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT-NIRS devices, CerOx™ and c-FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra-cranial structures from a genuine appraisal of cerebral perfusion. For non-invasive assessment of CBF-related parameters, the near-infrared spectroscopy still needs substantial improvement.
Subject(s)
Brain Death/diagnostic imaging , Cerebrovascular Circulation/physiology , Monitoring, Physiologic/methods , Spectroscopy, Near-Infrared/methods , Ultrasonography/methods , Adult , Aged , Aged, 80 and over , Brain Death/physiopathology , Female , Healthy Volunteers , Humans , Male , Middle Aged , Reference Values , Tomography, X-Ray ComputedABSTRACT
BACKGROUND AND PURPOSE: T-cells may play a role in the evolution of ischaemic damage and repair, but the ability to image these cells in the living brain after a stroke has been limited. We aim to extend the technique of real-time in situ brain imaging of T-cells, previously shown in models of immunological diseases, to models of experimental stroke. EXPERIMENTAL APPROACH: Male C57BL6 mice (6-8 weeks) (n= 3) received a total of 2-5 x 10(6) carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled lymphocytes from donor C57BL6 mice via i.v. injection by adoptive transfer. Twenty-four hours later, recipient mice underwent permanent left distal middle cerebral artery occlusion (MCAO) by electrocoagulation or by sham surgery under isoflurane anaesthesia. Female hCD2-green fluorescent protein (GFP) transgenic mice that exhibit GFP-labelled T-cells underwent MCAO. At 24 or 48 h post-MCAO, a sagittal brain slice (1500 microm thick) containing cortical branches of the occluded middle cerebral artery (MCA) was dissected and used for multiphoton laser scanning microscopy (MPLSM). KEY RESULTS: Our results provide direct observations for the first time of dynamic T-cell behaviour in living brain tissue in real time and herein proved the feasibility of MPLSM for ex vivo live imaging of immune response after experimental stroke. CONCLUSIONS AND IMPLICATIONS: It is hoped that these advances in the imaging of immune cells will provide information that can be harnessed to a therapeutic advantage.
Subject(s)
Brain/metabolism , Infarction, Middle Cerebral Artery/metabolism , Microscopy, Fluorescence, Multiphoton , Molecular Imaging , Molecular Probe Techniques , T-Lymphocytes/metabolism , Adoptive Transfer , Animals , Brain/immunology , Disease Models, Animal , Feasibility Studies , Female , Fluoresceins/metabolism , Fluorescent Dyes/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Infarction, Middle Cerebral Artery/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Succinimides/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Time FactorsABSTRACT
T-cells are known to play a role in the pathology associated with experimental cerebral malaria, although it has not previously been possible to examine their behaviour in brain. Using multiphoton laser scanning microscopy, we have examined the migration and movement of these cells in brain tissue. We believe that this approach will help define host-parasite interactions and examine how intervening in these relationships affects the development of cerebral pathology.
Subject(s)
Brain/immunology , Brain/pathology , Cell Movement/immunology , Malaria, Cerebral/immunology , Malaria, Cerebral/pathology , Microscopy, Confocal/methods , T-Lymphocytes/immunology , Animals , MiceABSTRACT
BACKGROUND: The goal of the study was to evaluate the effects of Cl-inhibitor (C1-INH), an endogenous glycoprotein endowed with multiple anti-inflammatory actions, on cognitive and histological outcome following controlled cortical impact (CCI) brain injury. METHODS: Male C57B1/6 mice (n=48) were subjected to CCI brain injury. After brain injury, animals randomly received an intravenous infusion of either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal volume, 150 microl at 10 min postinjury). Uninjured control mice received identical surgery and saline injection without brain injury. Cognitive function was evaluated at 4 weeks postinjury using the Morris Water Maze. Mice were subsequently sacrificed, the brains were frozen and serial sections were cut. Traumatic brain lesion was assessed by dividing the area of the ipsilateral hemisphere for the area of the contralateral one at the level of the injured area of the brain. FINDINGS: Brain-injured mice receiving C1-INH at 10 min postinjury showed attenuated cognitive dysfunction compared to brain-injured mice receiving saline (p < 0.01). These mice also showed a significantly reduced traumatic brain lesion compared to mice receiving saline (p < 0.01). Mice receiving C1-INH at 1 hour post injury did not show a significant improvement in either cognitive or histological outcome. Conclusions Our results suggest that administration of C1-INH at 10 minutes postinjury attenuates cognitive deficits and histological damage associated with traumatic brain injury.
Subject(s)
Brain Injuries/drug therapy , Complement C1 Inhibitor Protein/therapeutic use , Enzyme Inhibitors/therapeutic use , Analysis of Variance , Animals , Behavior, Animal/drug effects , Brain Injuries/physiopathology , Disease Models, Animal , Drug Administration Schedule , Locomotion/drug effects , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Reaction Time/drug effectsABSTRACT
BACKGROUND: Tumor necrosis factor (TNF)-alpha has been suggested to play both a deleterious and beneficial role in neurobehavioral dysfunction and recovery following traumatic brain injury (TBI). The goal of this study was to evaluate the specific role of tumor necrosis factor (TNF) receptors p55 and p75 in mediating cognitive outcome following controlled cortical impact (CCI) brain injury by comparing post-traumatic cognitive function in mice with genetically engineered deletion of the gene for either p55 (-/-) or p75 (-/-) receptors. METHOD: Male C57B1/6 mice (WT, n=29), and mice genetically engineered to delete p55 TNF (p55 (-/-), n=8) or p75 TNF (p75 (-/-), n=23) receptors were used. They were anesthetized with intraperitoneal (i.p.) administration of sodium pentobarbital (65 mg/kg) and subjected to CCI brain injury of moderate severity. Sham-injured control mice were anesthetized and surgically prepared similarly but they received no impact. Assessment of mRNA expression of inflammatory, proapoptotic and antiapoptotic genes was done by real time-polymerase chain reaction (RT-PCR). Cognitive outcome was evaluated at 4 weeks postinjury using the Morris water maze (MWM). FINDINGS: mRNA expression of inflammatory, proapoptotic and antiapoptotic genes prior to TBI did not reveal any baseline difference between p55 and p75 (-/-) mice. WT mice showed greater baseline expression of inflammatory genes. The learning ability of p55 (-/-) brain-injured mice was significantly better than that observed in p75 (-/-) brain-injured mice (p < 0.05). Cognitive learning in WT control mice fell between the p55 (-/-) and p75 (-/-) mice. CONCLUSIONS: These data suggest that TNF-alpha may both exacerbate cognitive dysfunction via p55 receptor and attenuate it via p75 receptor.
Subject(s)
Cognition Disorders/etiology , Cognition Disorders/genetics , Receptors, Tumor Necrosis Factor, Type II/deficiency , Receptors, Tumor Necrosis Factor, Type I/deficiency , Tumor Necrosis Factor Decoy Receptors/deficiency , Analysis of Variance , Animals , Behavior, Animal/physiology , Brain Injuries/complications , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Male , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Photic Stimulation/methods , RNA, Messenger/metabolism , Reaction Time/genetics , Space Perception/physiology , Time FactorsABSTRACT
Frequency noise of the local oscillator at even harmonics of the modulation frequency is known to contribute to the short-term instability of passive frequency standards. The mechanism by which this noise transfer takes place in Rb-cell standards is described here in a comprehensive approach that includes both signal theory methods and a time-dependent quantum mechanical analysis. The resulting calculated transfer coefficients for the various even harmonics are discussed in relationship with measured coefficients in an actual experiment.
