bioRxiv Subject Collection: Neuroscience's Journal
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Sunday, March 24th, 2024
| Time |
Event |
| 1:48a |
Do you see what I see? Diffusion imaging protocol heterogeneity biases ischemic core volume, location, and clinical associations in acute stroke
PurposeDiffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing ischemic stroke and identifying targets for emergency revascularization. Apparent diffusion coefficient (ADC) maps derived from DWI are commonly used to locate the infarct core, but they are not strictly quantitative and can vary across platforms and sites due to technical factors. This retrospective study was conducted to examine how differences in ADC map generation, resulting from varied protocols across platforms and sites, affect the determination of infarct core size, location, and related clinical outcomes in acute stroke.
MethodsIn this retrospective study, 726 acute anterior circulation stroke patients admitted to the Lausanne University Hospital between May 2018 and January 2021 were selected. DWI data were used to generate ADC maps as they would appear from different protocols: two simulated with low and medium angular resolution (4 and 12 diffusion gradient directions) and one with high angular resolution (20 directions). Using a DEFUSE like criteria and image post-processing, ischemic cores were localized; core volume, location, and associations to National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were compared between the two imaging sequences.
ResultsSignificant differences were observed in the ADC distribution within white matter, particularly in the kurtosis and skewness, with the segmented infarct core volume being higher in protocols with reduced angular resolution compared to the 20-directions data (7.63 ml vs. 3.78 ml). The volumetric differences persisted after correcting for age, sex, and type of intervention. Infarcted voxels locations varied significantly between the two protocols. This variability affected associations between infarct core volume and clinical scores, with lower associations observed for 4-directions data compared to 20-directions data for NIHSS at admission and after 24 hours, and mRS after 3 months, further confirmed by multivariate regression.
ConclusionsImaging protocol heterogeneity leads to significant changes in the ADC distribution, ischemic core location, size, and association with clinical scores. Work is needed in standardizing imaging protocols to improve the reliability of ADC as an imaging biomarker in stroke management.protocols to improve the reliability of ADC as an imaging biomarker in stroke management.
Key ResultsO_LIOrientation changes in diffusion imaging significantly impact ADC distribution and threshold-based infarct core volume determination, affecting multi-centric studies.
C_LIO_LILower number of directions in DWI acquisitions weakens associations between infarct volume measurements and clinical scores.
C_LIO_LIFindings emphasize the impact of DWI acquisition protocol heterogeneity and image processing on acute stroke workups.
C_LI | | 1:48a |
Hypothalamic Sex-Specific Metabolic Shift by Canagliflozin during Aging
The hypothalamus undergoes significant changes with aging and plays crucial roles in age-related metabolic alterations. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-diabetic agents that promote glucose excretion, and promote metabolic homeostasis. Recent studies have shown that SGLT2i, Canagliflozin (Cana), can extend the median survival of genetically heterogeneous UM-HET3 male mice and improve central metabolic control via increases in hypothalamic insulin responsiveness in aged males, as well as reduced age-associated hypothalamic inflammation. We studied the long- and short-term effects of Cana on hypothalamic metabolic control in UM-HET3 mice. We show that Cana treatment reduced body weight and fat mass in male mice that was associated with enhanced glucose tolerance and insulin sensitivity observed by 12 months. Indirect calorimetry showed that short-term Cana treatment (5 months) increased energy expenditure in male, but not female mice, at 12 months of age. Long-term Cana treatment (18 months) increased metabolic rates in both sexes, and markedly increasing formation of both orexigenic and anorexigenic projections to the paraventricular nucleus of the hypothalamus (PVH) mostly in females by 25 months. Hypothalamic RNA-sequencing analysis revealed sex-specific genes and signaling pathways related to insulin signaling, glycogen catabolic pathway, neuropeptide signaling, and mitochondrial function upregulated by Cana, with males showing a more pronounced and sustained effect on metabolic pathways at both age groups. Overall, our data provide critical evidence for sex-specific mechanisms that are impacted by Cana during aging suggesting key targets of hypothalamic Cana-induced neuroprotection for metabolic control. | | 2:17a |
Aberrant neuronal hyperactivation causes an age- and diet-dependent decline in associative learning behavior
The impairment of memory, cognition, and behavior during aging is generally thought to arise from diminished neuronal activities. The nematode Caenorhabditis elegans exhibits age-dependent declines in an associative learning behavior called thermotaxis. Genetic ablation of individual neurons revealed that an absence of either AWC sensory or AIA inter-neurons preserved the thermotaxis ability of aged animals. Calcium imaging showed age-dependent spontaneous hyperactivities in both neurons. The age-dependent neuronal hyperactivity and behavioral decline were ameliorated by changing diets. We further demonstrate that the enhanced activities of AWC and AIA were differentially dependent on the forms of neurotransmission mediated by neurotransmitters and neuropeptides. Together, our data provides evidence that aberrantly enhanced, not diminished, neuronal responses can impair behavior during aging.
One-Sentence SummaryEnhanced neuronal activity during aging impairs C. elegans learning behavior. | | 11:34p |
Retrieval of an ethanol-conditioned taste aversion promotes GABAergic plasticity in the insular cortex
Blunted sensitivity to ethanols aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuits potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic activity onto IC-BLA projections would be facilitated following the retrieval of an ethanol-conditioned taste aversion (CTA). Consistent with this hypothesis, frequency of mIPSCs was increased following retrieval of an ethanol-CTA across cell layers in IC-BLA projection neurons. This increase in GABAergic plasticity occurred in both a circuit-specific and learning-dependent manner. Additionally, local inhibitory inputs onto layer 2/3 IC-BLA projection neurons were greater in number and strength following ethanol-CTA. Finally, DREADD-mediated inhibition of IC parvalbumin-expressing cells blunted the retrieval of ethanol-CTA in male, but not female, mice. Collectively, this work implicates a circuit-specific and learning-dependent increase in GABAergic tone following retrieval of an ethanol-CTA, thereby advancing our understanding of how the aversive effects of ethanol are encoded in the brain.
Significance statementSensitivity to the aversive properties of ethanol contributes to motivation to consume alcohol. However, the plasticity-associated mechanisms through which ethanols aversive effects are represented within neural circuits are largely unidentified. In the present study, we used whole-cell patch clamp electrophysiology combined with synaptic input mapping to identify alterations in GABAergic plasticity within the insula, and within cells projecting from the insula to the basolateral amygdala. We demonstrate learning and circuit-specific alterations in GABAergic tone following retrieval of an ethanol-conditioned taste aversion, as well as a male-specific role for Parvalbumin-expressing interneurons in modulating the strength of an ethanol-conditioned taste aversion. Combined, these findings provide novel insights into how the aversive properties of ethanol are encoded within brain circuitry. |
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