Biology subjects

Corbin, D.

Publications and source records attributed to Corbin, 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↗

bioRxiv2023

Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice.

Mild-moderate traumatic brain injuries are common and while many individuals recover fully there is mounting clinical and epidemiological evidence that for a substantial subset, even when the acute TBI symptoms resolve, long term health can still be impacted. Individuals with a history of TBI are disproportionately vulnerable to many disease conditions including age-related neurodegeneration. These relationships are difficult to predict but these outcomes very likely interact with other disease risk factors such as cardiovascular disease. Here we tested the hypothesis that a mild pre-injury reduction in cerebral blood flow (bilateral carotid artery stenosis; BCAS) would impair recovery from TBI. Male and female mice underwent BCAS using steel microcoils around the carotid arteries, a mild-moderate closed-head TBI, or a combination of BCAS followed by TBI 30 days post-implantation. Cerebral blood flow, spatial learning and memory, axonal damage, and gene expression profiles were assessed. BCAS led to a [~]10% reduction in CBF, while TBI caused a similar decrease. However, mice exposed to both BCAS and TBI exhibited more pronounced reductions in CBF, associated with marked spatial learning and memory deficits, particularly in males. Axonal damage in male mice was also exacerbated by the combination of BCAS and TBI compared to either injury alone. Females exhibited spatial memory deficits associated with BCAS, but this was not exacerbated by TBI. We performed single nuclei RNA sequencing on male brain tissue to investigate the mechanisms underlying poorer long term functional outcomes in in TBI-BCAS animals. TBI and BCAS independently altered gene expression profiles in neurons and glia but in most cases BCAS and TBI together produced markedly different transcriptional patterns than either challenge alone. Overall, our findings reveal that the presence of mild reductions in cerebrovascular blood flow as a proxy for preexisting cardiovascular disease significantly exacerbated TBI outcomes in male but not female mice, indicating that even relatively mild comorbidities could significantly alter TBI outcomes and increase the probability of secondary disease processes.

neuroscience↗

bioRxiv2020

A Simulation Study Investigating Potential Diffusion-based MRI Signatures of Microstrokes

Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n=5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p<0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p<0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0=3) and shorter readout TE (<16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials.

neuroscience↗