Biology subjects

Mester, J. R.

Publications and source records attributed to Mester, J. R..

2 recordsLinked to original sources

bioRxiv2026

Chronic Stress Exacerbates Long-term Microvascular Network Dysfunction Following Brain Trauma

BackgroundPreexisting factors are among the strongest predictors of recovery following traumatic brain injury (TBI), with chronic stress closely associated with permanent disability and worse long-term outcomes. While chronic cerebrovascular dysfunction is linked to these poor trajectories, as impaired blood flow regulation drives secondary disease progression, the mechanisms regulating this vascular failure remain incompletely understood. Crucially, how premorbid chronic stress and TBI disrupt the fundamental coordination of the cerebrovascular network post-injury remains unknown. MethodsTo elucidate this coordination at rest and in response to increased neuronal activity, we used a model of three repeated moderate closed cortical impacts comorbid with chronic stress induced by social isolation (SI) post-weaning. Our previously developed vascular analysis pipeline (NOVAS3D) was employed to estimate changes in vascular radii across cerebrovasculature proximal to neuronal activation. Arteries and veins were annotated in the imaged volumes to allow for blood flow simulations. ResultsUsing graph-based network analysis, we demonstrate that TBI, when compounded with chronic stress, critically disrupts the long-range coordination of the capillary network. Specifically, the functional coordination of radius changes between nearby, non-adjacent capillaries was reduced by 40{+/-}20% in TBI+SI mice relative to controls. Consequently, simulations estimated that the vascular networks in TBI+SI mice experienced a 68{+/-}7% reduction in arterial red blood cell velocity (VRBC) responses to neuronal activation. These network-wide impairments were fundamentally driven by severely blunted vessel reactivity, including a 28{+/-}7% decrease in the magnitude of arteriolar dilations and a 47{+/-}7% decrease in the magnitude of arteriolar constrictions. ConclusionThese findings provide a mechanistic foundation for worse clinical outcomes seen in TBI patients with comorbid chronic stress, identifying arteriolar reactivity and long-range capillary coordination as critical therapeutic targets to mitigate secondary injury and improve long-term recovery.

neuroscience↗

bioRxiv2024

A Deep Learning Pipeline for Mapping in situ Network-level Neurovascular Coupling in Multi-photon Fluorescence Microscopy

1Functional hyperaemia is a well-established hallmark of healthy brain function, whereby local brain blood flow adjusts in response to a change in the activity of the surrounding neurons. Although functional hyperemia has been extensively studied at the level of both tissue and individual vessels, vascular network-level coordination remains largely unknown. To bridge this gap, we developed a deep learning-based computational pipeline that uses two-photon fluorescence microscopy images of cerebral microcirculation to enable automated reconstruction and quantification of the geometric changes across the microvascular network, comprising hundreds of interconnected blood vessels, pre and post-activation of the neighbouring neurons. The pipelines utility was demonstrated in the Thy1-ChR2 optogenetic mouse model, where we observed network-wide vessel radius changes to depend on the photostimulation intensity, with both dilations and constrictions occurring across the cortical depth, at an average of 16.1{+/-}14.3 m (mean{+/-}stddev) away from the most proximal neuron for dilations; and at 21.9{+/-}14.6 m away for constrictions. We observed a significant heterogeneity of the vascular radius changes within vessels, with radius adjustment varying by an average of 24 {+/-} 28% of the resting diameter, likely reflecting the heterogeneity of the distribution of contractile cells on the vessel walls. A graph theory-based network analysis revealed that the assortativity of adjacent blood vessel responses rose by 152 {+/-} 65% at 4.3 mW/mm2 of blue photostimulation vs. the control, with a 4% median increase in the efficiency of the capillary networks during this level of blue photostimulation in relation to the baseline. Interrogating individual vessels is thus not sufficient to predict how the blood flow is modulated in the network. Our computational pipeline, to be made openly available, enables tracking of the microvascular network geometry over time, relating caliber adjustments to vessel wall-associated cells state, and mapping network-level flow distribution impairments in experimental models of disease.

neuroscience↗