scholarly journals Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain

2016 ◽  
Vol 37 (5) ◽  
pp. 1735-1747 ◽  
Author(s):  
R David Andrew ◽  
Yi-Ting Hsieh ◽  
C Devin Brisson

We examined in live coronal slices from rat and mouse which brain regions generate potassium-triggered spreading depolarization (SDKt). This technique simulates cortical spreading depression, which underlies migraine aura in the intact brain. An SDKt episode was evoked by increasing bath [K+]o and recorded as a propagating front of elevated light transmittance representing transient neuronal swelling in gray matter of neocortex, hippocampus, striatum, and thalamus. In contrast, SDKt was not imaged in hypothalamic nuclei or brainstem with exception of those nuclei near the dorsal brainstem surface. In rat slices, single neurons were whole-cell current clamped during SDKt. “Higher” neurons depolarized to near zero millivolts indicating SDKt generation. In contrast, seven types of neurons in hypothalamus and brainstem only slowly depolarized without generating SDKt, supporting our imaging findings. Therefore, SDKt is not a default of CNS neurons but rather displays a region-specific susceptibility, similar to anoxic depolarization, which we have proposed is correlated with a region’s vulnerability to traumatic brain injury. In the higher brain, SDKt may be a vestigial spreading depolarization that originally evolved to shut down and vasoconstrict gray matter regions more exposed to impact and contusion.

2021 ◽  
Vol 11 (3) ◽  
pp. 374
Author(s):  
Tomoyo Morita ◽  
Minoru Asada ◽  
Eiichi Naito

Self-consciousness is a personality trait associated with an individual’s concern regarding observable (public) and unobservable (private) aspects of self. Prompted by previous functional magnetic resonance imaging (MRI) studies, we examined possible gray-matter expansions in emotion-related and default mode networks in individuals with higher public or private self-consciousness. One hundred healthy young adults answered the Japanese version of the Self-Consciousness Scale (SCS) questionnaire and underwent structural MRI. A voxel-based morphometry analysis revealed that individuals scoring higher on the public SCS showed expansions of gray matter in the emotion-related regions of the cingulate and insular cortices and in the default mode network of the precuneus and medial prefrontal cortex. In addition, these gray-matter expansions were particularly related to the trait of “concern about being evaluated by others”, which was one of the subfactors constituting public self-consciousness. Conversely, no relationship was observed between gray-matter volume in any brain regions and the private SCS scores. This is the first study showing that the personal trait of concern regarding public aspects of the self may cause long-term substantial structural changes in social brain networks.


1992 ◽  
Vol 12 (2) ◽  
pp. 230-237 ◽  
Author(s):  
Marleen J. Verhaegen ◽  
Michael M. Todd ◽  
David S. Warner ◽  
Bruce James ◽  
Julie B. Weeks

Cerebral blood flow was measured by the H2 clearance method 30 and 60 min after the implantation of 300, 250, 125, or 50 μm diameter platinum–iridium electrodes 2 mm deep into the right parietal cortex of normothermic, normocarbic halothane-anesthetized rats. Another group of animals had 50 μm electrodes inserted 1 mm. In all animals, the presence or absence of a wave of spreading depression (SD) was noted at the time of implantation, with recordings made with glass micropipettes. H2 flow values were compared with those measured in gray matter from the same anatomical region (but from different rats), using [3H]nicotine. The incidence of SD ranged from 60% following insertion of 300 μm electrodes to 0% with 50 μm electrodes. H2 clearance flows also varied with electrode size, from 77 ± 21 ml 100 g−1 min−1 (mean ± standard deviation) with 300 μm electrodes to 110 ± 31 and 111 ± 16 ml 100 g−1 min−1 with 125 and 50 μm electrodes, respectively (insertion depth of 2 mm). A CBF value of 155 ± 60 ml 100 g−1 min−1 was obtained with 50 μm electrodes inserted only 1 mm. Cortical gray matter blood flow measured with [3H]nicotine was 154 ± 35 ml 100 g−1 min−1. When the role of SD in subsequent flow measurements was examined, there was a gradual increase in CBF between 30 and 60 min after electrode insertion in those animals with SD, while no such change was seen in rats without SD. These results indicate that the choice of electrode size and implantation depth influences the measurement of CBF by H2 clearance. CBF values equivalent to those obtained with isotopic techniques can be acutely obtained with small (50 μm diameter) electrodes inserted 1 mm into the cortex. While the occurrence of SD does influence CBF in the period immediately after implantation, a relationship between electrode size and measured flow is present that is independent of SD.


2021 ◽  
pp. 089198872098891
Author(s):  
Regina Eun Young Kim ◽  
Robert Douglas Abbott ◽  
Soriul Kim ◽  
Robert Joseph Thomas ◽  
Chang-Ho Yun ◽  
...  

This study aimed to evaluate the effect of sleep duration on brain structures in the presence versus absence of sleep apnea in middle-aged and older individuals. The study investigated a population-based sample of 2,560 individuals, aged 49-80 years. The presence of sleep apnea and self-reported sleep duration were examined in relation to gray matter volume (GMV) in total and lobar brain regions. We identified ranges of sleep duration associated with maximal GMV using quadratic regression and bootstrap sampling. A significant quadratic association between sleep duration and GMV was observed in total and lobar brain regions of men with sleep apnea. In the fully adjusted model, optimal sleep durations associated with peak GMV between brain regions ranged from 6.7 to 7.0 hours. Shorter and longer sleep durations were associated with lower GMV in total and 4 sub-regions of the brain in men with sleep apnea.


1998 ◽  
Vol 88 (6) ◽  
pp. 1058-1065 ◽  
Author(s):  
Kenneth R. Wagner ◽  
Guohua Xi ◽  
Ya Hua ◽  
Marla Kleinholz ◽  
Gabrielle M. de Courten-Myers ◽  
...  

Object. The authors previously demonstrated, in a large-animal intracerebral hemorrhage (ICH) model, that markedly edematous (“translucent”) white matter regions (> 10% increases in water contents) containing high levels of clotderived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the concentrations of high-energy phosphate, carbohydrate substrate, and lactate in these and other perihematomal white and gray matter regions during the early hours following experimental ICH. Methods. The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a physiologically controlled model in pigs (weighing approximately 7 kg each) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water contents were then measured in white and gray matter located ipsi- and contralateral to the hematomas, and metabolite concentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentrations increased two- to fivefold compared with control during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5 hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 µmol/g) at all times. In gyral gray matter overlying the hematoma, water contents and glycogen levels were significantly increased at 5 and 8 hours, whereas lactate levels were increased two- to fourfold at all times. Conclusions. These results, which demonstrate normal to increased high-energy phosphate and carbohydrate substrate concentrations in edematous perihematomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present, lactate accumulation in edematous white matter is not caused by stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the blood entering the brain's extracellular space during ICH are several-fold higher than normal levels, the authors speculate, on the basis of work reported by Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced aerobic glycolysis and lactate is generated at a rate that exceeds utilization.


2020 ◽  
Author(s):  
Christoph Fraenz ◽  
Dorothea Metzen ◽  
Christian J. Merz ◽  
Helene Selpien ◽  
Nikolai Axmacher ◽  
...  

AbstractResearch has shown that fear acquisition, in reaction to potentially harmful stimuli or situations, is characterized by pronounced interindividual differences. It is likely that such differences are evoked by variability in the macro- and microstructural properties of brain regions involved in the processing of threat or safety signals from the environment. Indeed, previous studies have shown that the strength of conditioned fear reactions is associated with the cortical thickness or volume of various brain regions. However, respective studies were exclusively targeted at single brain regions instead of whole brain networks. Here, we tested 60 young and healthy individuals in a differential fear conditioning paradigm while they underwent fMRI scanning. In addition, we acquired T1-weighted and multi-shell diffusion-weighted images prior to testing. We used task-based fMRI data to define global brain networks which exhibited increased BOLD responses towards CS+ or CS- presentations, respectively. From these networks, we obtained mean values of gray matter density, neurite density, and neurite orientation dispersion. We found that mean gray matter density averaged across the CS+ network was significantly correlated with the strength of conditioned fear reactions quantified via skin conductance response. Measures of neurite architecture were not associated with conditioned fear reaction in any of the two networks. Our results extend previous findings on the relationship between brain morphometry and fear learning. Most importantly, our study is the first to introduce neurite imaging to fear learning research and discusses how its implementation can be improved in future research.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elizabeth Farrow ◽  
Andreas G. Chiocchetti ◽  
Jack C. Rogers ◽  
Ruth Pauli ◽  
Nora M. Raschle ◽  
...  

AbstractConduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual’s sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes. Here, we combined an epigenome-wide association study with structural neuroimaging in 51 females with CD and 59 typically developing (TD) females to examine DNA methylation in relation to CD, CU traits, and gray matter volume (GMV). We demonstrate an inverse pattern of correlation between CU traits and methylation of a chromosome 1 region in CD females (positive) as compared to TD females (negative). The identified region spans exon 1 of the SLC25A24 gene, central to energy metabolism due to its role in mitochondrial function. Increased SLC25A24 methylation was also related to lower GMV in multiple brain regions in the overall cohort. These included the superior frontal gyrus, prefrontal cortex, and supramarginal gyrus, secondary visual cortex and ventral posterior cingulate cortex, which are regions that have previously been implicated in CD and CU traits. While our findings are preliminary and need to be replicated in larger samples, they provide novel evidence that CU traits in females are associated with methylation levels in a fundamentally different way in CD and TD, which in turn may relate to observable variations in GMV across the brain.


2001 ◽  
Vol 85 (1) ◽  
pp. 414-424 ◽  
Author(s):  
I. Joshi ◽  
R. D. Andrew

Focal ischemia evokes a sudden loss of membrane potential in neurons and glia of the ischemic core termed the anoxic depolarization (AD). In metabolically compromised regions with partial blood flow, peri-infarct depolarizations (PIDs) further drain energy reserves, promoting acute and delayed neuronal damage. Visualizing and quantifying the AD and PIDs and their acute deleterious effects are difficult in the intact animal. In the present study, we imaged intrinsic optical signals to measure changes in light transmittance in the mouse coronal hemi-brain slice during AD generation. The AD was induced by oxygen/glucose deprivation (OGD) or by ouabain exposure. Potential neuroprotective strategies using glutamate receptor antagonists or reduced temperature were tested. Eight minutes of OGD ( n = 18 slices) or 4 min of 100 μM ouabain ( n = 14) induced a focal increase of increased light transmittance (LT) in neocortical layers II/III that expanded concentrically to form a wave front coursing through neocortex and independently through striatum. The front was coincident with a negative voltage shift in extracellular potential. Wherever the LT front (denoting cell swelling) propagated, a decrease in LT (denoting dendritic beading) followed in its wake. In addition the evoked field potential was permanently lost, indicating neuronal damage. Glutamate receptor antagonists did not block the onset and propagation of AD or the extent of irreversible damage post-AD. Lowering temperature to 25–30°C protected the tissue from OGD damage by inhibiting AD onset. This study shows that anoxic depolarization evoked by global ischemia-like conditions is a spreading process that is focally initiated at multiple sites in cortical and subcortical gray. The combined energy demands of O2/glucose deprivation and the AD greatly exacerbate neuronal damage. Glutamate receptor antagonists neither block the AD in the ischemic core nor, we propose, block recurrent PID arising close to the core.


2015 ◽  
Vol 11 (8) ◽  
pp. e1004414 ◽  
Author(s):  
Ghanim Ullah ◽  
Yina Wei ◽  
Markus A Dahlem ◽  
Martin Wechselberger ◽  
Steven J Schiff

2019 ◽  
Vol 14 (11) ◽  
pp. 1187-1195
Author(s):  
Patrick Bach ◽  
Ulrich Frischknecht ◽  
Svenja Klinkowski ◽  
Melanie Bungert ◽  
Damian Karl ◽  
...  

Abstract Opioid-dependent patients are highly sensitized to negative social feedback, and increased social rejection sensitivity was linked to adverse treatment outcome, but its neurobiological underpinnings have not been understood yet. The present study investigated gray matter (GM) volume differences between 19 opioid maintenance treatment (OMT) patients and 20 healthy controls using magnetic resonance imaging and voxel-based morphometry. Associations of GM volumes with subjective feelings of exclusion and inclusion during a social ostracism (Cyberball) paradigm, with rejection sensitivity, social interaction anxiety and social phobia were explored. OMT patients displayed smaller GM volume in the bilateral insula and inferior frontal gyri. Psychometric and task data showed that patients reported significantly higher rejection sensitivity, social anxiety and social phobia scores and felt more excluded and less included during the social ostracism paradigm. Smaller GM volume in the insula was associated with higher subjective exclusion, lower subjective inclusion and higher rejection sensitivity, social anxiety and social phobia scores. Findings indicate that structural deficits in emotion- and anxiety-processing brain regions in OMT patients are associated with increased social rejection sensitivity. As social rejection is a potential trigger for relapse, patients might benefit from therapeutic strategies that promote social integration.


2019 ◽  
Vol 62 (4) ◽  
pp. 483-494
Author(s):  
Christina Andica ◽  
Koji Kamagata ◽  
Takuya Hayashi ◽  
Akifumi Hagiwara ◽  
Wataru Uchida ◽  
...  

Abstract Purpose The reproducibility of neurite orientation dispersion and density imaging (NODDI) metrics in the human brain has not been explored across different magnetic resonance (MR) scanners from different vendors. This study aimed to evaluate the scan–rescan and inter-vendor reproducibility of NODDI metrics in white and gray matter of healthy subjects using two 3-T MR scanners from two vendors. Methods Ten healthy subjects (7 males; mean age 30 ± 7 years, range 23–37 years) were included in the study. Whole-brain diffusion-weighted imaging was performed with b-values of 1000 and 2000 s/mm2 using two 3-T MR scanners from two different vendors. Automatic extraction of the region of interest was performed to obtain NODDI metrics for whole and localized areas of white and gray matter. The coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were calculated to assess the scan–rescan and inter-vendor reproducibilities of NODDI metrics. Results The scan–rescan and inter-vendor reproducibility of NODDI metrics (intracellular volume fraction and orientation dispersion index) were comparable with those of diffusion tensor imaging (DTI) metrics. However, the inter-vendor reproducibilities of NODDI (CoV = 2.3–14%) were lower than the scan–rescan reproducibility (CoV: scanner A = 0.8–3.8%; scanner B = 0.8–2.6%). Compared with the finding of DTI metrics, the reproducibility of NODDI metrics was lower in white matter and higher in gray matter. Conclusion The lower inter-vendor reproducibility of NODDI in some brain regions indicates that data acquired from different MRI scanners should be carefully interpreted.


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