Biology subjects

Kureli, G.

Publications and source records attributed to Kureli, G..

3 recordsLinked to original sources

bioRxiv2025

Torsional Force by Helical Pericytes Regulates Blood Flow in Downstream Capillaries

This study investigates the contractile properties of downstream capillaries, which are traditionally regarded as passive conduits, and addresses ongoing debates surrounding blood flow regulation. It is widely accepted that these capillaries passively dilate in response to increased blood flow in upstream microvessels, and that the helical pericytes located on them lack contractile capability, largely due to the absence of detectable -SMA expression. Challenging this prevailing view, we demonstrate that downstream capillary pericytes do express both -SMA and Myosin11, as shown using in situ hybridization on whole-mount intact retinas--unlike prior studies that relied on dissociated cells. Furthermore, Forster resonance energy transfer (FRET) analysis reveals that -SMA and Myosin11 are in sufficiently close proximity to permit actomyosin bridge cycling, a process essential for contraction. We also show that pericyte contraction can be inhibited by disrupting this molecular interaction. Distinct from the nodal constrictions caused by circular pericyte processes in upstream microvessels, we identify torsional contractions in the downstream capillaries in the retina of living mice using two-photon laser scanning microscopy (TPLSM), which regulates blood flow. These contractions provide direct evidence that downstream capillaries actively contribute to blood flow regulation. Notably, such contractions were overlooked in previous TPLSM studies that monitored only luminal diameter, unless the specialized analytical techniques we employed were applied. Our 3D modeling confirms that these torsional contractions correlate with the helical morphology of pericytes in downstream capillaries--a structure previously thought incapable of producing significant constrictive force. In conclusion, our findings provide direct evidence that downstream pericytes play an active role in regulating blood flow. They highlight a previously unrecognized mechanism--torsional contraction--that aligns with the helical structure of these pericytes and contributes to flow regulation in small-caliber capillaries located nearest to regions of high oxygen demand. TEASERDownstream Capillary Pericytes Express -SMA and Regulate Flow via Torsional Contraction

neuroscience↗

bioRxiv2024

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

neuroscience↗

bioRxiv2022

High Throughput Detection of Capillary Stalling Events with Bessel Beam Two-Photon Microscopy

Disruptions in capillary flow have the potential to drive pathology across numerous diseases. But our understanding of the temporal and spatial dynamics of these events are hindered by slow volumetric imaging rates and the reliance on laborious manual analysis to process data. To address the challenges of increasing volumetric imaging speed, we use a custom-built Bessel beam two-photon microscope for efficient volumetric imaging of the capillary network. We demonstrate its ability to continuously monitor roughly 200 capillaries for capillary flow stoppages (i.e. stalling events) at a frame rate of approximately 0.5 Hz and develop a semi-automated correlation-based approach for identifying these stalling events. We applied our system and algorithm in a photothrombotic model of stroke and show elevated levels of stalling 1-week post-stroke in regions both within and outside of the stroke region, demonstrating that stalling may have impacts on stroke recovery that extend past the acute stage.

neuroscience↗