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Cell Death Discovery May 2024Deceased donor liver transplantation (LT) is a crucial lifesaving option for patients with end-stage liver diseases. Although donation after brain death (DBD) remains...
Deceased donor liver transplantation (LT) is a crucial lifesaving option for patients with end-stage liver diseases. Although donation after brain death (DBD) remains the main source of donated organs, exploration of donation after circulatory death (DCD) addresses donor scarcity but introduces challenges due to warm ischemia. While technical advances have improved outcomes, challenges persist, with a 13% mortality rate within the first year. Delving into liver transplantation complexities reveals the profound impact of molecular signaling on organ fate. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation play a pivotal role, influencing inflammatory responses. The NLRP3 inflammasome, found in hepatocytes, contributes to inflammation, fibrosis, and liver cell death. This study explores these dynamics, shedding light on potential biomarkers and therapeutic targets. Samples from 36 liver transplant patients were analyzed for ASC specks detection and inflammasome-related gene expression. Liver biopsies, obtained before and after cold ischemia storage, were processed for immunofluorescence, qRT-PCR, and Western blot. One year post-LT clinical follow-up included diagnostic procedures for complications, and global survival was assessed. Immunofluorescence detected activated inflammasome complexes in fixed liver tissues. ASC specks were identified in hepatocytes, showing a trend toward more specks in DCD livers. Likewise, inflammasome-related gene expression analysis indicated higher expression in DCD livers, decreasing after cold ischemia. Similar results were found at protein level. Patients with increased ASC specks staining exhibited lower overall survival rates, correlating with IL1B expression after cold ischemia. Although preliminary, these findings offer novel insights into utilizing direct detection of inflammasome activation in liver tissue as a biomarker. They suggest its potential impact on post-transplant outcomes, potentially paving the way for improved diagnostic approaches and personalized treatment strategies in LT.
PubMed: 38816358
DOI: 10.1038/s41420-024-02042-y -
AJNR. American Journal of Neuroradiology May 2024The abnormalities of long arm of chromosome 18 (18q) constitute a complex spectrum. We aimed to systematically analyze their MRI features. We hypothesized that there...
BACKGROUND AND PURPOSE
The abnormalities of long arm of chromosome 18 (18q) constitute a complex spectrum. We aimed to systematically analyze their MRI features. We hypothesized that there would be variable but recognizable white matter and structural patterns in this cohort.
MATERIALS AND METHODS
In this retrospective cohort study, we included pediatric patients with a proven abnormality of 18q between 2000-2022. An age and sex matched control cohort was also constructed.
RESULTS
Thirty-six cases, median MRI age 19.6 months (4.3 - 59.3), satisfied our inclusion criteria. Majority were females (25, 69%, F:M ratio 2.2:1). Fifty MR imaging studies were analyzed and 35 (70%) had delayed myelination. Two independent readers scored brain myelination with excellent interrater reliability. Three recognizable evolving MRI patterns with distinct age distributions and improving myelination scores were identified - PMD-like (9.9 months, 37), intermediate (22 months, 48) and washed-out pattern (113.6 months, 53). Etiologically, MRIs were analyzed across three subgroups - 18q- (34, 69%), trisomy 18 (10, 21%) and ring chromosome 18 (5, 10%). Ring chromosome 18 had the highest myelination lag (27, P value = 0.005) and multifocal white matter changes (P value = 0.001). Trisomy 18 had smaller pons and cerebellar dimensions (APD pons P value = 0.002, CC vermis P value <0.001 and TCD P value = 0.04).
CONCLUSIONS
In this cohort of 18q chromosomal abnormalities, MRI revealed recognizable patterns correlating with improving brain myelination. Imaging findings appear to be on a continuum with more severe white matter abnormalities in ring chromosome 18 and greater prevalence of structural abnormalities of pons and cerebellum in trisomy 18.
ABBREVIATIONS
18q-: 18q deletion; CC: corpus callosum; CC-APD: CC anteroposterior diameter; FOD: fronto-occipital diameter; TCD: transverse cerebellar diameter; APD: anteroposterior diameter; CCD: craniocaudal diameter; MBP: myelin basic protein; PMD: Pelizaeus-Merzbacher Disease; GWMD: gray-white matter differentiation.
PubMed: 38816019
DOI: 10.3174/ajnr.A8361 -
Brain Research Sep 2024Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus...
Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI. The majority of TBIs are mild, yet long-term cognitive deficits and increased susceptibility for further injury can accumulate after each repetitive mild TBI. As a potential treatment for restoring cognitive function and daytime sleepiness after injury psychostimulants, including methylphenidate (MPH) that increase levels of NE within the PFC, are being prescribed "off-label". The impact of mild and repetitive mild TBI on the LC-NE system remains limited. Therefore, we determined the extent of LC-NE and arousal dysfunction and response to therapeutic doses of MPH in rats following experimentally induced single and repetitive mild TBI. Microdialysis measures of basal NE efflux from the medial PFC and arousal measures were significantly lower after repetitive mild TBI. Females showed higher baseline PFC-NE efflux than males following single and repetitive mild TBI. In response to MPH challenge, males exhibited a blunted PFC-NE response and persistent arousal levels following repetitive mild TBI. These results provide critical insight into the role of catecholamine system dysfunction associated with cognitive deficits following repeated injury, outcome differences between sex/gender, and lack of success of MPH as an adjunctive therapy to improve cognitive function following injury.
Topics: Animals; Male; Norepinephrine; Female; Rats, Sprague-Dawley; Prefrontal Cortex; Central Nervous System Stimulants; Methylphenidate; Brain Concussion; Rats; Brain Injuries, Traumatic; Locus Coeruleus; Arousal; Microdialysis
PubMed: 38815643
DOI: 10.1016/j.brainres.2024.149040 -
ELife May 2024Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are...
Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca sensitivity of release and a loosened coupling between voltage-gated Ca channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.
Topics: Animals; Mice, Knockout; Glycine; Mice; Trapezoid Body; Synaptic Transmission; Neural Cell Adhesion Molecules; Superior Olivary Complex; Brain Stem; Synapses; Neurons; Cell Adhesion Molecules, Neuronal; Nerve Tissue Proteins; Neurexins; Calcium-Binding Proteins
PubMed: 38814174
DOI: 10.7554/eLife.94315 -
Neuroreport Jul 2024Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative...
Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system. We prepared brain slices of the mouse brainstem and performed patch-clamp recording in bushy cells in the anteroventral cochlear nucleus, with or without Danshensu incubation for 1 h. QX-314 was used internally to block Na+ current, while tetraethylammonium and 4-aminopyridine were used to isolate different subtypes of K+ current. We found that Danshensu of 100 μm decreased the input resistance of bushy cells by approximately 60% and shifted the voltage threshold of spiking positively by approximately 7 mV, resulting in significantly reduced excitability. Furthermore, we found this reduced excitability by Danshensu was caused by enhanced voltage-gated K+ currents in these neurons, including both low voltage-activated IK,A, by approximately 100%, and high voltage-activated IK,dr, by approximately 30%. Lastly, we found that the effect of Danshensu on K+ currents was dose-dependent in that no enhancement was found for Danshensu of 50 μm and Danshensu of 200 μm failed to cause significantly more enhancement on K+ currents when compared to that of 100 μm. We found that Danshensu reduced neuronal excitability in the central nervous system by enhancing voltage-gated K+ currents, providing mechanistic support for its neuroprotective effect widely seen in vivo.
Topics: Animals; Mice; Neurons; Lactates; Cochlear Nucleus; Patch-Clamp Techniques; Action Potentials; Male; Potassium Channels; Mice, Inbred C57BL
PubMed: 38813908
DOI: 10.1097/WNR.0000000000002047 -
Frontiers in Psychology 2024In bilingual communities, knowing the language each speaker uses may support language separation and, later, guide language use in a context-appropriate manner. Previous...
INTRODUCTION
In bilingual communities, knowing the language each speaker uses may support language separation and, later, guide language use in a context-appropriate manner. Previous research has shown that infants begin to form primary associations between the face and the language used by a speaker around the age of 3 months. However, there is still a limited understanding of how robust these associations are and whether they are influenced by the linguistic background of the infant. To answer these questions, this study explores monolingual and bilingual infants' ability to form face-language associations throughout the first year of life.
METHODS
A group of 4-, 6-, and 10-month-old Spanish and/or Catalan monolingual and bilingual infants were tested in an eye-tracking preferential-looking paradigm ( = 156). After the infants were familiarized with videos of a Catalan and a Spanish speaker, they were tested in two types of test trials with different task demands. First, a Silent test trial assessed primary face-language associations by measuring infants' visual preference for the speakers based on the language they had previously used. Then, two Language test trials assessed more robust face-language associations by measuring infants' ability to match the face of each speaker with their corresponding language.
RESULTS
When measuring primary face-language associations, both monolingual and bilingual infants exhibited language-based preferences according to their specific exposure to the languages. Interestingly, this preference varied with age, with a transition from an initial familiarity preference to a novelty preference in older infants. Four-month-old infants showed a preference for the speaker who used their native/dominant language, while 10-month-old infants preferred the speaker who used their non-native/non-dominant language. When measuring more robust face-language associations, infants did not demonstrate signs of consistently matching the faces of the speakers with the language they had previously used, regardless of age or linguistic background.
DISCUSSION
Overall, the results indicate that while both monolingual and bilingual infants before the first year of life can form primary face-language associations, these associations remain fragile as infants seemed unable to maintain them when tested in a more demanding task.
PubMed: 38813567
DOI: 10.3389/fpsyg.2024.1393836 -
Journal of Affective Disorders Sep 2024Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than...
BACKGROUND
Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than diagnostic markers.
METHODS
We explored associations between personality and ED-related mental health symptoms using canonical correlation analyses. We investigated personality risk profiles in a longitudinal sample, associating personality at age 14 with onset of mental health symptoms at ages 16 or 19. Diagnostic markers were identified in a sample of young adults with anorexia nervosa (AN, n = 58) or bulimia nervosa (BN, n = 63) and healthy controls (n = 47).
RESULTS
Two significant premorbid risk profiles were identified, successively explaining 7.93 % and 5.60 % of shared variance (R). The first combined neuroticism (canonical loading, r = 0.68), openness (r = 0.32), impulsivity (r = 0.29), and conscientiousness (r = 0.27), with future onset of anxiety symptoms (r = 0.87) and dieting (r = 0.58). The other, combined lower agreeableness (r = -0.60) and lower anxiety sensitivity (r = -0.47), with future deliberate self-harm (r = 0.76) and purging (r = 0.55). Personality profiles associated with "core psychopathology" in both AN (R = 80.56 %) and BN diagnoses (R = 64.38 %) comprised hopelessness (r = 0.95, 0.87) and neuroticism (r = 0.93, 0.94). For BN, this profile also included impulsivity (r = 0.60). Additionally, extraversion (r = 0.41) was associated with lower depressive risk in BN.
LIMITATIONS
The samples were not ethnically diverse. The clinical cohort included only females. There was non-random attrition in the longitudinal sample.
CONCLUSIONS
The results suggest neuroticism and impulsivity as risk and diagnostic markers for EDs, with neuroticism and hopelessness as shared diagnostic markers. They may inform the design of more personalised prevention and intervention strategies.
Topics: Humans; Female; Personality; Young Adult; Adolescent; Anorexia Nervosa; Male; Neuroticism; Longitudinal Studies; Feeding and Eating Disorders; Bulimia Nervosa; Adult; Impulsive Behavior; Risk Factors; Anxiety; Comorbidity; Anxiety Disorders
PubMed: 38810783
DOI: 10.1016/j.jad.2024.05.132 -
Current Biology : CB Jun 2024An epidemic of sleep loss currently affects modern societies worldwide and is implicated in numerous physiological disorders, including pain sensitization, although few...
An epidemic of sleep loss currently affects modern societies worldwide and is implicated in numerous physiological disorders, including pain sensitization, although few studies have explored the brain pathways affected by active sleep deprivation (ASD; e.g., due to recreation). Here, we describe a neural circuit responsible for pain sensitization in mice treated with 9-h non-stress ASD. Using a combination of advanced neuroscience methods, we found that ASD stimulates noradrenergic inputs from locus coeruleus (LC) to glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HL). Moreover, artificial inhibition of this LC→S1HL pathway alleviates ASD-induced pain sensitization in mice, while chemogenetic activation of this pathway recapitulates the pain sensitization observed following ASD. Our study thus implicates activation of the LC→S1HL pathway in ASD-induced pain sensitization, expanding our fundamental understanding of the multisystem interplay involved in pain processing.
Topics: Animals; Mice; Sleep Deprivation; Locus Coeruleus; Pain; Somatosensory Cortex; Male; Norepinephrine; Mice, Inbred C57BL; Adrenergic Neurons; Neurons; Neural Pathways
PubMed: 38810638
DOI: 10.1016/j.cub.2024.05.005 -
PLoS Computational Biology May 2024The dorsal (DRN) and median (MRN) raphe are important nuclei involved in similar functions, including mood and sleep, but playing distinct roles. These nuclei have a...
The dorsal (DRN) and median (MRN) raphe are important nuclei involved in similar functions, including mood and sleep, but playing distinct roles. These nuclei have a different composition of neuronal types and set of neuronal connections, which among other factors, determine their neuronal dynamics. Most works characterize the neuronal dynamics using classic measures, such as using the average spiking frequency (FR), the coefficient of variation (CV), and action potential duration (APD). In the current study, to refine the characterization of neuronal firing profiles, we examined the neurons within the raphe nuclei. Through the utilization of nonlinear measures, our objective was to discern the redundancy and complementarity of these measures, particularly in comparison with classic methods. To do this, we analyzed the neuronal basal firing profile in both nuclei of urethane-anesthetized rats using the Shannon entropy (Bins Entropy) of the inter-spike intervals, permutation entropy of ordinal patterns (OP Entropy), and Permutation Lempel-Ziv Complexity (PLZC). Firstly, we found that classic (i.e., FR, CV, and APD) and nonlinear measures fail to distinguish between the dynamics of DRN and MRN neurons, except for the OP Entropy. We also found strong relationships between measures, including the CV with FR, CV with Bins entropy, and FR with PLZC, which imply redundant information. However, APD and OP Entropy have either a weak or no relationship with the rest of the measures tested, suggesting that they provide complementary information to the characterization of the neuronal firing profiles. Secondly, we studied how these measures are affected by the oscillatory properties of the firing patterns, including rhythmicity, bursting patterns, and clock-like behavior. We found that all measures are sensitive to rhythmicity, except for the OP Entropy. Overall, our work highlights OP Entropy as a powerful and useful quantity for the characterization of neuronal discharge patterns.
Topics: Animals; Rats; Action Potentials; Neurons; Nonlinear Dynamics; Models, Neurological; Raphe Nuclei; Male; Computational Biology; Rats, Sprague-Dawley
PubMed: 38805554
DOI: 10.1371/journal.pcbi.1012111 -
Current Medical Imaging May 2024This study aimed to evaluate the diagnostic value of X-Map reconstruction based on Dual-Energy Computed Tomography (DECT) in acute ischemic stroke (AIS).
OBJECTIVE
This study aimed to evaluate the diagnostic value of X-Map reconstruction based on Dual-Energy Computed Tomography (DECT) in acute ischemic stroke (AIS).
METHODS
Sixty-six cases of suspected AIS patients hospitalized from November, 2021 to April, 2022 were retrospectively selected. DECT, Computed Tomography Perfusion imaging (CTP), Computed Tomography Angiography (CTA), and MRI were all performed within 24 hours after symptom onset. As the gold standard for diagnosing AIS, a total of 53 patients were diagnosed with AIS based on the diffusion-weighted imaging positive results in MRI. The Chi-square test was used to evaluate the diagnostic efficacy of AIS among X-Map, CTP, and CTA.
RESULTS
In the 53 patients with confirmed ASI, a total of 72 lesions were detected, including in the frontal lobes (n=33), parietal lobes (n=7), temporal lobes (n=12), basal ganglia regions (n=12), thalamus (n=3), and pons (n=5). The case detection rate of X-Map for AIS was similar to that of CTP (p=0.151) but was significantly higher than that of CTA (p<0.001). In terms of diagnostic efficacy, among the total 66 patients enrolled, X-Map achieved a higher diagnostic sensitivity (85%) than CTP and CTA. However, CTP achieved the best diagnostic specificity (84.6%) and diagnostic accuracy (77.4%) among the diagnostic tools used.
CONCLUSION
X-Map provides a better or equal clinical value for the diagnosis of AIS as compared to CTA and CTP, respectively, highlighting its potential in clinical applications.
PubMed: 38803185
DOI: 10.2174/0115734056294190240522113039