scholarly journals MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xuan Zhang ◽  
Merle G. Paule ◽  
Glenn D. Newport ◽  
Fang Liu ◽  
Ralph Callicott ◽  
...  

Background. The inhalation anesthetics nitrous oxide (N2O) and isoflurane (ISO) are used in surgical procedures for human infants. Injury to the central nervous system is often accompanied by localization of activated microglia or astrocytosis at the site of injury. The tracer that targets to the peripheral benzodiazepine receptor (PBR), [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]-FEPPA), has been reported as a sensitive biomarker for the detection of neuronal damage/inflammation. Methods. On postnatal day (PND) 5 or 6 rhesus monkey neonates were exposed to a mixture of N2O/oxygen and ISO for 8 hours and control monkeys were exposed to room air. MicroPET/CT images with [18F]-FEPPA were obtained for each monkey 1 day, one week, three weeks, and 6 months after the anesthetic exposure. Results. The radiotracer quickly distributed into the brains of both treated and control monkeys on all scan days. One day after anesthetic exposure, the uptake of [18F]-FEPPA was significantly increased in the temporal lobe. One week after exposure, the uptake of [18F]-FEPPA in the frontal lobe of treated animals was significantly greater than that in controls. Conclusions. These findings suggest that microPET imaging is capable of dynamic detection of inhaled anesthetic-induced brain damage in different brain regions of the nonhuman primate.

2020 ◽  
Vol 52 (8) ◽  
pp. 864-874
Author(s):  
Bing Chen ◽  
Yanjun Liu ◽  
Yirong Cai ◽  
Dan Tang ◽  
Saihong Xu ◽  
...  

Abstract During the rapidly developing and sensitive period of the central nervous system (CNS), a harmful stimulus may have serious consequences. The effect of anesthetic exposure on the development of the offspring’s CNS during pregnancy is still unclear and has been widely concerned. In the present study, we compared the susceptibility of the hippocampus with those of other brain regions in offsprings when the mother mice were exposed to repeated sevoflurane. We found that other than affecting motor sensation, emotion, or social behavior of offspring mice, repeated sevoflurane exposure induced significant memory deficiency. Compared with other brain regions, the hippocampus, which is the key component of the brain serving for learning and memory, was more vulnerable to repeated sevoflurane exposure. We also found that repeated sevoflurane exposure to mother mice could inhibit the axon development of hippocampal neurons. We also predicted that N6-methyladenosine modification of mRNA might play an essential role in the vulnerability of the hippocampus to sevoflurane, while the underlying cellular mechanism needs to be explored in the future. Our study may provide a new perspective for studying the mechanism of hippocampus-specific injury induced by sevoflurane exposure.


Author(s):  
D. M. DePace

The majority of blood vessels in the superior cervical ganglion possess a continuous endothelium with tight junctions. These same features have been associated with the blood brain barrier of the central nervous system and peripheral nerves. These vessels may perform a barrier function between the capillary circulation and the superior cervical ganglion. The permeability of the blood vessels in the superior cervical ganglion of the rat was tested by intravenous injection of horseradish peroxidase (HRP). Three experimental groups of four animals each were given intravenous HRP (Sigma Type II) in a dosage of.08 to.15 mg/gm body weight in.5 ml of.85% saline. The animals were sacrificed at five, ten or 15 minutes following administration of the tracer. Superior cervical ganglia were quickly removed and fixed by immersion in 2.5% glutaraldehyde in Sorenson's.1M phosphate buffer, pH 7.4. Three control animals received,5ml of saline without HRP. These were sacrificed on the same time schedule. Tissues from experimental and control animals were reacted for peroxidase activity and then processed for routine transmission electron microscopy.


Author(s):  
Erbu Yarci ◽  
Cuneyt Tayman ◽  
Ufuk Cakir ◽  
Utku Serkant

Background:: Hyperviscosity of blood secondary to polycythemia results in increased resistance to blood flow and decrease in delivery of oxygen. Objective:: To evaluate whether serum endocan, NSE and IMA levels can be compared in terms of endothelial injury/ dysfunction and neuronal damage in term neonates with polycythemia who underwent PET. Methods:: 38 symptomatic polycythemic newborns having PET and 38 healthy newborns were included in the study. Blood samples for endocan, NSE and IMA were taken at only postnatal 24 hours of age in the control group and in polycytemia group just before PET, at 24 and 72 hours after PET. Results:: The polycythemia group had higher serum endocan(1073,4 ± 644,8 vs. 378,8 ± 95,9ng/ml; p<0.05), IMA(1,32 ± 0,34 vs.0,601 ± 0,095absorbance unit; p<0.05) and NSE(44,7 ± 4,3 vs. 26,91 ± 7,12μg/l; p<0.05) levels than control group before the PET procedure. At 24 hours after PET, IMA(0,656 ± 0,07 vs. 0,601 ± 0,095absorbance unit; p<0.05) and endocan(510,9 ± 228,6 vs. 378,8 ± 95,9ng/ml; p<0.05) levels were closer to the control group, being still statistically significant higher. NSE levels decreased to control group levels having no difference between the PET and control groups at 24 hours after PET (28,98 ± 6,5 vs. 26,91 ± 7,12μg/l; p>0.05). At 72 hours after PET the polycythemia and control groups did not differ statistically for IMA, endocan and NSE levels (p>0.05). Conclusion:: Serum endocan and IMA levels can be used as a biomarker for endothelial damage / dysfunction and tissue hypoxia in infants with symptomatic polycytemia.


2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huoyin Zhang ◽  
Shiyunmeng Zhang ◽  
Jiachen Lu ◽  
Yi Lei ◽  
Hong Li

AbstractPrevious studies in humans have shown that brain regions activating social exclusion overlap with those related to attention. However, in the context of social exclusion, how does behavioral monitoring affect individual behavior? In this study, we used the Cyberball game to induce the social exclusion effect in a group of participants. To explore the influence of social exclusion on the attention network, we administered the Attention Network Test (ANT) and compared results for the three subsystems of the attention network (orienting, alerting, and executive control) between exclusion (N = 60) and inclusion (N = 60) groups. Compared with the inclusion group, the exclusion group showed shorter overall response time and better executive control performance, but no significant differences in orienting or alerting. The excluded individuals showed a stronger ability to detect and control conflicts. It appears that social exclusion does not always exert a negative influence on individuals. In future research, attention to network can be used as indicators of social exclusion. This may further reveal how social exclusion affects individuals' psychosomatic mechanisms.


1968 ◽  
Vol 66 (3) ◽  
pp. 355-364 ◽  
Author(s):  
H. E. Webb ◽  
D. G. D. Wight ◽  
G. Wiernik ◽  
G. S. Platt ◽  
C. E. G. Smith

Summary1. Irradiation in a whole body dose of 200 rads or more increased the sensitivity of mice to intraperitoneal infection with Langat virus so that the LD 50 was increased to about the intracerebral LD 50.2. In mice given 500 rads before infection: (a) viraemia was prolonged by about 5 days; (b) the IgM response was depressed; (c) the IgG response was delayed by about 3 days and depressed in titre; (d) virus concentration in the brain rose continuously until death on about the tenth day while in the controls it reached a peak on the fifth day then subsided; (e) histological changes in the CNS were delayed and minimal even at death; (f) irradiated mice died with little evidence of paralysis while the controls died with severe paralysis.3. In irradiated mice, protection was observed when antibody was administered on the third day following infection. Antibody given on the 3 days after infection to control mice aggravated the disease.4. The results in this and the preceding paper are discussed in relation to the pathogenesis of encephalitis. It is concluded that neuronal damage is caused both by virus multiplication in neurones and by damage superimposed by inflammatory changes with associated oedema and hypoxia. The inflammatory changes appear to be due to an allergic reaction to virus-antibody complexes formed in the circulation and in the central nervous system.We are grateful to Miss S. J. Illavia, B.Sc., and Miss G. E. Fairbairn for their skilled technical assistance; to the Department of Radiotherapy at St Thomas's Hospital for providing time and staff to help with the irradiation experiments; and to Mr S. Peto of the Microbiological Research Establishment for statistical advice.This work was made possible by a generous grant from the Wellcome Trust and the Endowment Funds of St Thomas's Hospital.


2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 704
Author(s):  
Yingyu Zhou ◽  
Wanyi Qiu ◽  
Yimei Wang ◽  
Rong Wang ◽  
Tomohiro Takano ◽  
...  

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria. Furthermore, we evaluated the interaction between cerebral metabolites and intestinal microbiota via Pearson correlations. The prediction results suggested that Firmicutes were possibly controlled by neuron integrity, cerebral inflammation, and neurotransmitters, and Bacteroidetes in mouse intestines might be related to cerebral aerobic respiration and the glucose cycle. Such results also implied that Actinobacteria probably affected cerebral energy metabolism. These findings suggested that β-elemene has regulatory effects on the imbalanced microbiota-gut-brain axis caused by obesity and, therefore, would contribute to the future study in on the interplay between cerebral metabolites from different brain regions and the intestinal microbiota of mice.


2012 ◽  
Vol 32 (4) ◽  
pp. 731-744 ◽  
Author(s):  
James FM Myers ◽  
Lula Rosso ◽  
Ben J Watson ◽  
Sue J Wilson ◽  
Nicola J Kalk ◽  
...  

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume ( VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that Zolpidem caused a significant VT decrease (~10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean ± s.d.: 71% ± 41%), presumed to reflect α1-subtype binding, but not another (13% ± 22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.


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