Spinal cord injury and vascular function: Evidence from diameter matched vessels

The effect of a spinal cord injury (SCI) on vascular function has been clouded by both the physiological and mathematical bias of assessing vasodilation in arteries with differing diameters both above and below the lesion and when comparing with healthy, non-disabled controls (CTRL). Thus, we measured vascular function, with flow mediated vasodilation (FMD), in 10 SCI and 10 CTRL with all arteries matched for diameter (≈0.5cm): brachial (BA, arm, functional-limb in both groups) and popliteal artery (PA, leg, disused-limb in SCI, functional-limb in CTRL). PA %FMD was significantly attenuated in SCI (5.6±0.6%) compared to CTRL (8.4±1.3%), with no difference in the BA (SCI: 8.6±0.9%; CTRL: 8.7±0.7%). However, unlike the arm, where muscle mass was preserved, the legs of the SCI were significantly smaller than CTRL (~70%). Thus, reactive hyperemia (RH), which is heavily dependent upon the volume of muscle occluded, in the PA was attenuated in the SCI (144±22ml) compared to CTRL (258±16ml), but not different in the BA. Consequently, shear rate was significantly diminished in the PA of the SCI, such that %FMD/shear rate (vascular responsiveness) was actually greater in the SCI (1.5±0.1%・s-1) than CTRL (1.2±0.1%・s-1). Of note, this was significantly greater than both their own BA (0.9±0.1%・s-1) and that of the CTRL (0.9±0.1%・s-1). Therefore, examining vessels of similar size, this study reveals normal vascular function above the lesion and vascular dysfunction below the lesion. However, below the lesion there was, actually, evidence of increased vascular responsiveness in this population.

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Acute heat stress reduces biomarkers of endothelial activation but not macro- or microvascular dysfunction in cervical spinal cord injury

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00693.2018 ◽

2019 ◽

Vol 316 (3) ◽

pp. H722-H733 ◽

Cited By ~ 6

Author(s):

Geoff B. Coombs ◽

Otto F. Barak ◽

Aaron A. Phillips ◽

Tanja Mijacika ◽

Zoe K. Sarafis ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Femoral Artery ◽

Vascular Function ◽

Vascular Dysfunction ◽

Water Immersion ◽

Reactive Hyperemia ◽

Endothelial Activation ◽

Hot Water ◽

Cord Injury

Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunction in SCI and the acute effects of passive heating. Fifteen participants with cervical SCI and 15 uninjured control (CON) participants underwent ultrasound assessments of vascular function and venous blood sampling for biomarkers of endothelial activation (i.e., CD62e+) and apoptosis (i.e., CD31+/42b−) before and after a 60-min exposure to lower limb hot water immersion (40°C). In SCI, macrovascular endothelial function was reduced in the brachial artery [SCI: 4.8 (3.2)% vs. CON: 7.6 (3.4)%, P = 0.04] but not the femoral artery [SCI: 3.7 (2.6)% vs. CON: 4.0 (2.1)%, P = 0.70]. Microvascular function, via reactive hyperemia, was ~40% lower in SCI versus CON in both the femoral and brachial arteries ( P < 0.01). Circulating concentrations of CD62e+ were elevated in SCI versus CON [SCI: 152 (106) microparticles/µl vs. CON: 58 (24) microparticles/µl, P < 0.05]. In response to heating, macrovascular and microvascular function remained unchanged, whereas increases (+83%) and decreases (−93%) in antegrade and retrograde shear rates, respectively, were associated with heat-induced reductions of CD62e+ concentrations in SCI to levels similar to CON ( P = 0.05). These data highlight the potential of acute heating to provide a safe and practical strategy to improve vascular function in SCI. The chronic effects of controlled heating warrant long-term testing. NEW & NOTEWORTHY Individuals with cervical level spinal cord injury exhibit selectively lower flow-mediated dilation in the brachial but not femoral artery, whereas peak reactive hyperemia was lower in both arteries compared with uninjured controls. After 60 min of lower limb hot water immersion, femoral artery blood flow and shear patterns were acutely improved in both groups. Elevated biomarkers of endothelial activation in the spinal cord injury group decreased with heating, but these biomarkers remained unchanged in controls.

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Using Multiscale Entropy to Assess the Efficacy of Local Cooling on Reactive Hyperemia in People with a Spinal Cord Injury

Entropy ◽

10.3390/e21010090 ◽

2019 ◽

Vol 21 (1) ◽

pp. 90 ◽

Cited By ~ 3

Author(s):

Fuyuan Liao ◽

Tim Yang ◽

Fu-Lien Wu ◽

Chunmei Cao ◽

Ayman Mohamed ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Blood Flow ◽

Temperature Change ◽

Pressure Ulcers ◽

Reactive Hyperemia ◽

Multiscale Entropy ◽

Intervention Period ◽

Local Cooling ◽

Cord Injury

Pressure ulcers are one of the most common complications of a spinal cord injury (SCI). Prolonged unrelieved pressure is thought to be the primary causative factor resulting in tissue ischemia and eventually pressure ulcers. Previous studies suggested that local cooling reduces skin ischemia of the compressed soft tissues based on smaller hyperemic responses. However, the effect of local cooling on nonlinear properties of skin blood flow (SBF) during hyperemia is unknown. In this study, 10 wheelchair users with SCI and 10 able-bodied (AB) controls underwent three experimental protocols, each of which included a 10-min period as baseline, a 20-min intervention period, and a 20-min period for recovering SBF. SBF was measured using a laser Doppler flowmetry. During the intervention period, a pressure of 60 mmHg was applied to the sacral skin, while three skin temperature settings were tested, including no temperature change, a decrease by 10 °C, and an increase by 10 °C, respectively. A multiscale entropy (MSE) method was employed to quantify the degree of regularity of blood flow oscillations (BFO) associated with the SBF control mechanisms during baseline and reactive hyperemia. The results showed that under pressure with cooling, skin BFO both in people with SCI and AB controls were more regular at multiple time scales during hyperemia compared to baseline, whereas under pressure with no temperature change and particularly pressure with heating, BFO were more irregular during hyperemia compared to baseline. Moreover, the results of surrogate tests indicated that changes in the degree of regularity of BFO from baseline to hyperemia were only partially attributed to changes in relative amplitudes of endothelial, neurogenic, and myogenic components of BFO. These findings support the use of MSE to assess the efficacy of local cooling on reactive hyperemia and assess the degree of skin ischemia in people with SCI.

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Recurrent autonomic dysreflexia exacerbates vascular dysfunction after spinal cord injury

The Spine Journal ◽

10.1016/j.spinee.2010.09.018 ◽

2010 ◽

Vol 10 (12) ◽

pp. 1108-1117 ◽

Cited By ~ 31

Author(s):

Nima Alan ◽

Leanne M. Ramer ◽

Jessica A. Inskip ◽

Saeid Golbidi ◽

Matt S. Ramer ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vascular Dysfunction ◽

Autonomic Dysreflexia ◽

Cord Injury

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Transcriptomic Screening of Microvascular Endothelial Cells Implicates Novel Molecular Regulators of Vascular Dysfunction after Spinal Cord Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.76 ◽

2008 ◽

Vol 28 (11) ◽

pp. 1771-1785 ◽

Cited By ~ 26

Author(s):

Richard L Benton ◽

Melissa A Maddie ◽

Christopher A Worth ◽

Edward T Mahoney ◽

Theo Hagg ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vascular Dysfunction ◽

Fluorescein Isothiocyanate ◽

Microvascular Dysfunction ◽

Cell Counting ◽

Protein Levels ◽

Cord Injury ◽

Biochemical Analyses ◽

High Degree

Microvascular dysfunction is a critical pathology that underlies the evolution of secondary injury mechanisms after traumatic spinal cord injury (SCI). However, little is known of the molecular regulation of endothelial cell (EC) plasticity observed acutely after injury. One reason for this is the relative lack of methods to quickly and efficiently obtain highly enriched spinal microvascular ECs for high-throughput molecular and biochemical analyses. Adult C57BI/6 mice received an intravenous injection of fluorescein isothiocyanate (FITC)-conjugated Lycopersicon esculentum lectin, and FITC-lectin bound spinal microvessels were greatly enriched by fluorescence-activated cell sorter (FACS) purification. This technique allows for rapid (< 1.5 h postmortem) isolation of spinal cord microvascular ECs (smvECs). The results from cell counting, reverse-transcription polymerase chain reaction (RT-PCR), and western blot analyses show a high degree of EC enrichment at mRNA and protein levels. Furthermore, a focused EC biology microarray analysis identified multiple mRNAs dramatically increased in the EC compartment 24 h after SCI, which is a time point associated with the pathologic loss of spinal vasculature. These included thrombospondin-1, CCL5/RANTES, and urokinase plasminogen activator, suggesting they may represent targets for therapeutic intervention. Furthermore, these novel methodologic approaches will likely facilitate the discovery of molecular regulators of endothelial dysfunction in a variety of central nervous system (CNS) disorders including stroke and other neurodegenerative diseases having a vascular component.

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Intermittent Pneumatic Compression Effects on Leg Blood Flow and Vascular Function in Spinal Cord Injury

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000487517.22321.92 ◽

2016 ◽

Vol 48 ◽

pp. 840

Author(s):

Lena M. Cialdella ◽

Preston L. Bell ◽

David R. Dolbow ◽

Daniel P. Credeur

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Blood Flow ◽

Vascular Function ◽

Intermittent Pneumatic Compression ◽

Leg Blood Flow ◽

Cord Injury ◽

Compression Effects

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Flow Mediated Vasodilation And Limb Disuse Following A Spinal Cord Injury

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000495473.33793.71 ◽

2014 ◽

Vol 46 ◽

pp. 667

Author(s):

Massimo Venturelli ◽

Markus Amann ◽

Gwenael Layec ◽

Joel D. Trinity ◽

Stephen Ives ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cord Injury ◽

Flow Mediated Vasodilation

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Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon

Neurosurgical FOCUS ◽

10.3171/foc.2008.25.11.e2 ◽

2008 ◽

Vol 25 (5) ◽

pp. E2 ◽

Cited By ~ 365

Author(s):

James W. Rowland ◽

Gregory W. J. Hawryluk ◽

Brian Kwon ◽

Michael G. Fehlings

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Apoptotic Cell ◽

Vascular Dysfunction ◽

Mechanical Injury ◽

Current Status ◽

Emerging Therapies ◽

Cord Injury ◽

Central Myelin ◽

Do So

This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho–associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.

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Ultrafast Doppler imaging and Ultrasound Localization Microscopy reveal the complexity of vascular rearrangement in chronic spinal lesion

10.21203/rs.3.rs-1001156/v2 ◽

2022 ◽

Author(s):

Benoit Beliard ◽

Chaimae Ahmanna ◽

Elodie Tiran ◽

Kadia Kante ◽

Thomas Deffieux ◽

...

Keyword(s):

Spinal Cord ◽

Vascular Function ◽

Vascular Dysfunction ◽

Imaging Modality ◽

Doppler Imaging ◽

Localization Microscopy ◽

Ultrasound Localization ◽

Statistical Correlations ◽

Cord Injury

Abstract Acute spinal cord injury (SCI) leads to severe damage to the microvascular network. The process of spontaneous repair is accompanied by formation of new blood vessels; their functionality, however, presumably very important for functional recovery, has never been clearly established, as most studies so far used fixed tissues. Here, combining ultrafast Doppler imaging and Ultrasound Localization Microscopy (ULM) on the same animals, we proceeded at a detailed analysis of structural and functional vascular alterations associated with the establishment of chronic SCI, both at macroscopic and microscopic scales. Using a standardized animal model of SCI, our results demonstrate striking hemodynamic alterations in several subparts of the spinal cord: a reduced blood velocity in the lesion site, and an asymmetrical hypoperfusion caudal but not rostral to the lesion. In addition, the worsening of many evaluated parameters at later time points suggests that the neoformed vascular network is not yet fully operational, and reveals ULM as an efficient in vivo readout for spinal cord vascular alterations. Finally, we show statistical correlations between the diverse biomarkers of vascular dysfunction and SCI severity. The imaging modality developed here will allow evaluating recovery of vascular function over time in pre-clinical models of SCI. Also, used on SCI patients in combination with other quantitative markers of neural tissue damage, it may help classifying lesion severity and predict possible treatment outcomes in patients.

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