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Hydrogen sulfide (H 2 S) is a toxin affecting the cardiovascular, respiratory, and central nervous systems. Acute H 2 S exposure is associated with a high rate of mortality and morbidity. The precise pathophysiology of H 2 S-induced death is a controversial topic; however, inhibition of the respiratory center in the brainstem is commonly cited as a cause of death. There is a knowledge gap on toxicity and toxic mechanisms of acute H 2 S poisoning on the brainstem, a brain region responsible for regulating many reflective and vital functions. Serotonin (5-HT), dopamine (DA), and γ-aminobutyric acid (GABA) play a role in maintaining a normal stable respiratory rhythmicity. We hypothesized that the inhibitory respiratory effects of H 2 S poisoning are mediated by 5-HT in the respiratory center of the brainstem. Male C57BL/6 mice were exposed once to an LCt 50 concentration of H 2 S (1000 ppm). Batches of surviving mice were euthanized at 5 min, 2 h, 12 h, 24 h, 72 h, and on day 7 post-exposure. Pulmonary function, vigilance state, and mortality were monitored during exposure. The brainstem was analyzed for DA, 3,4-dehydroxyphenyl acetic acid (DOPAC), 5-HT, 5-hydroxyindoleatic acid (5-HIAA), norepinephrine (NE), GABA, glutamate, and glycine using HPLC. Enzymatic activities of monoamine oxidases (MAO) were also measured in the brainstem using commercial kits. Neurodegeneration was assessed using immunohistochemistry and magnetic resonance imaging. Results showed that DA and DOPAC were significantly increased at 5 min post H 2 S exposure. However, by 2 h DA returned to normal. Activities of MAO were significantly increased at 5 min and 2 h post-exposure. In contrast, NE was significantly decreased at 5 min and 2 h post-exposure. Glutamate was overly sensitive to H 2 S-induced toxicity manifesting a time-dependent concentration reduction throughout the 7 day duration of the study. Remarkably, there were no changes in 5-HT, 5-HIAA, glycine, or GABA concentrations. Cytochrome c oxidase activity was inhibited but recovered by 24 h. Neurodegeneration was observed starting at 72 h post H 2 S exposure in select brainstem regions. We conclude that acute H 2 S exposure causes differential effects on brainstem neurotransmitters. H 2 S also induces neurodegeneration and biochemical changes in the brainstem. Additional work is needed to fully understand the implications of both the short- and long-term effects of acute H 2 S poisoning on vital functions regulated by the brainstem., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Hydrogen sulfide (H 2 S) is a gaseous molecule found naturally in the environment, and as an industrial byproduct, and is known to cause acute death and induces long-term neurological disorders following acute high dose exposures. Currently, there is no drug approved for treatment of acute H 2 S-induced neurotoxicity and/or neurological sequelae. Lack of a deep understanding of pathogenesis of H 2 S-induced neurotoxicity has delayed the development of appropriate therapeutic drugs that target H 2 S-induced neuropathology. RNA sequencing analysis was performed to elucidate the cellular and molecular mechanisms of H 2 S-induced neurodegeneration, and to identify key molecular elements and pathways that contribute to H 2 S-induced neurotoxicity. C57BL/6J mice were exposed by whole body inhalation to 700 ppm of H 2 S for either one day, two consecutive days or 4 consecutive days. Magnetic resonance imaging (MRI) scan analyses showed H 2 S exposure induced lesions in the inferior colliculus (IC) and thalamus (TH). This mechanistic study focused on the IC. RNA Sequencing analysis revealed that mice exposed once, twice, or 4 times had 283, 193 and 296 differentially expressed genes (DEG), respectively (q-value < 0.05, fold-change> 1.5). Hydrogen sulfide exposure modulated multiple biological pathways including unfolded protein response, neurotransmitters, oxidative stress, hypoxia, calcium signaling, and inflammatory response in the IC. Hydrogen sulfide exposure activated PI3K/Akt and MAPK signaling pathways. Pro-inflammatory cytokines were shown to be potential initiators of the modulated signaling pathways following H 2 S exposure. Furthermore, microglia were shown to release IL-18 and astrocytes released both IL-1β and IL-18 in response to H 2 S. This transcriptomic analysis data revealed complex signaling pathways involved in H 2 S-induced neurotoxicity and may provide important associated mechanistic insights., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Functional T1ρ mapping has been proposed as a method to assess pH and metabolism dynamics in the brain with high spatial and temporal resolution. The purpose of this work is to describe and evaluate a variant of the spin-locked echo-planar imaging sequence for functional T1ρ mapping at 3T. The proposed sequence rapidly acquires a time series of T1ρ maps with 4.0second temporal resolution and 10 slices of volumetric coverage. Simulation, phantom, and in vivo experiments are used to evaluate many aspects of the sequence and its implementation including fidelity of measured T1ρ dynamics, potential confounds to the T1ρ response, imaging parameter tradeoffs, time series analysis approaches, and differences compared to blood oxygen level dependent functional magnetic resonance imaging. It is shown that the high temporal resolution and volumetric coverage of the sequence are obtained with some expense including underestimation of the T1ρ response, sensitivity to T1 dynamics, and reduced signal-to-noise ratio. In vivo studies using a flashing checkerboard functional magnetic resonance imaging paradigm suggest differences between T1ρ and blood oxygen level dependent activation patterns. Possible sources of the functional T1ρ response and potential sequence improvements are discussed. The capability of T1ρ to map whole-brain pH and metabolism dynamics with high temporal and spatial resolution is potentially unique and warrants further investigation and development., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Prostate-specific deletion of Pten in mice has been reported to recapitulate histological progression of human prostate cancer. To improve on this model, we introduced the conditional ROSA26 luciferase reporter allele to monitor prostate cancer progression via bioluminescence imaging and extensively backcrossed mice onto the albino C57BL/6 genetic background to address variability in tumor kinetics and to enhance imaging sensitivity. Bioluminescence signal increased rapidly in Pten(p-/-) mice from 3 to 11 weeks, but was much slower from 11 to 52 weeks. Changes in bioluminescence signal were correlated with epithelial proliferation. Magnetic resonance imaging revealed progressive increases in prostate volume, which were attributed to excessive fluid retention in the anterior prostate and to expansion of the stroma. Development of invasive prostate cancer in 52-week-old Pten(p-/-) mice was rare, indicating that disease progression was slowed relative to that in previous reports. Tumors in these mice exhibited a spontaneous inflammatory phenotype and were rapidly infiltrated by myeloid-derived suppressor cells. Although Pten(p-/-) tumors responded to androgen withdrawal, they failed to exhibit relapsed growth for up to 1 year. Taken together, these data identify a mild prostate cancer phenotype in C57BL/6 prostate-specific Pten-deficient mice, reflecting effects of the C57BL/6 genetic background on cancer progression. This model provides a platform for noninvasive assessment of how genetic and environmental risk factors may affect disease progression., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)