Biology subjects

Chantler, P. D.

Publications and source records attributed to Chantler, P. D..

3 recordsLinked to original sources

bioRxiv2025

Nicotine Influence on Vascular and Neurocognitive Function with In-utero Electronic Cigarette Exposure

Emerging studies find arteriolar dysfunction in offspring with in-utero electronic cigarette (Ecig) exposure, but the long-term effect on offsprings cerebrovascular vascular and neurocognitive health is poorly understood. Ecigs provides a unique opportunity to directly evaluate the contributions of inhaled nicotine from the vehicle e-liquid - which was not possible with traditional cigarettes. Moreover, many Ecigs have variable power settings, which can alter the toxicity of the aerosol cloud produced. We hypothesize maternal vaping at different wattages will have variable effects on cerebrovascular function in the offspring, and that these effects would be independent of nicotine. We used time-mated female Sprague-Dawley rats with Ecig exposure from gestation day (GD)2-21. We studied male and female offspring for vascular and neurocognitive function at 1-, 3-, 6- and 12-months of age. We found that, both sexes, offspring with in-utero exposure (at 5w and 30w Ecig conditions) exhibited impaired middle cerebral artery (MCA) reactivity. While the magnitude of impairment was greater at higher that lower watts, Ecig at 5-watts still exhibited significant impairments in MCA function (suggesting the harm threshold for blood vessels is very low). Vascular dysfunction was evident with or without nicotine in the e-liquid, but nicotine exposure resulted in short-term memory deficits, evidence of neuronal damage, and increased astrocyte interaction with endothelial cells in 6- and 12-month-old offspring. We also observed altered expression of clock genes and antioxidant signaling pathways, along with a decrease in sirtuin-1 expression, decreased ratio of beta-amyloid A 42/40 protein expression, and increased in NOX1, which are consistent with redox imbalance, neuroinflammation, and advancing cellular senescence. These preclinical data provide evidence suggesting that in utero exposure to Ecigs from maternal vaping can be expected to adversely affect the brain health of offspring in their adult life and that neurocognitive outcomes are worsened with exposure to nicotine. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/638202v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1e7a7a1org.highwire.dtl.DTLVardef@1ae5bceorg.highwire.dtl.DTLVardef@d323eorg.highwire.dtl.DTLVardef@5db4af_HPS_FORMAT_FIGEXP M_FIG C_FIG Created in BioRender

developmental biology↗

bioRxiv2017

Monocyte-Lymphocyte Cross-Communication Via Soluble CD163 Directly Links Innate Immune System Activation And Adaptive Immune System Suppression Following Ischemic Stroke

CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n=39), neurologically asymptomatic controls (n=20), and stroke mimics (n=20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

neuroscience↗

bioRxiv2017

Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population.

PurposeOur group recently identified a ten gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population.\n\nMethodsPublically available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset, along with 23 cardiovascular disease controls were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes were extracted, compared between groups, and evaluated for their discriminatory ability at each time point.\n\nResultsWe observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points.\n\nConclusionsThese findings confirm the diagnostic robustness of the previously identified pattern of differential expression in independent patient population, and further suggest that it is temporally stable over the first 24 hours of stroke pathology.

genomics↗