Biology subjects

Al-Khazraji, B. K.

Publications and source records attributed to Al-Khazraji, B. K..

3 recordsLinked to original sources

bioRxiv2025

Cerebrovascular Responses to Static and Rhythmic Handgrip Exercises

Handgrip exercise (HGE) is a safe, accessible exercise modality shown to improve cardiovascular health and is particularly promising for individuals with limited mobility who cannot engage in traditional exercise. Given that contraction type and intensity influence systemic cardiorespiratory variables that affect cerebral blood flow regulation, this study examined the acute systemic hemodynamic and cerebrovascular responses to static and rhythmic HGE protocols at varying intensities. Thirty-three healthy young adults (17 males; 16 females age 22(1) years) performed four separate 5-minute HGE protocols in a randomized order: static HGE at 15% (S15) of maximal voluntary contraction (MVC), static HGE at 30% MVC, rhythmic HGE at 30% MVC, rhythmic HGE at 60% (R60) MVC. We hypothesized that rhythmic HGE at higher intensities would produce the greatest cerebrovascular responses due to enhanced venous return and cardiac output, while static HGE at higher intensities would elicit the greatest systemic (i.e., blood pressure, HR, ventilation) responses. Cerebral (middle cerebral artery blood velocity [MCAv] and cerebrovascular conductance index [MCACVCi], internal carotid artery [ICA] diameter, velocity, blood flow, and shear rate) and systemic hemodynamics (systolic [SBP], diastolic [DBP], mean arterial pressure [MAP], heart rate [HR], cardiac output [CO]), and end-tidal carbon dioxide (PETCO2) levels were averaged over the final 30s of each minute of exercise. There was a significant time and protocol interaction effect on HR (p<0.001). We found significant main effects of exercise protocol for MCAv (p<0.001), MCACVCi (p<0.001), ICA diameter (p=0.01) and blood flow (p=0.001), and PETCO2 (p=0.002). Greatest increases in MCAv alongside the largest reduction in ICA blood flow occurred in R60. The greatest increase in MCACVCi and ICA blood flow (from baseline) occurred in R30 compared to other protocols. In addition to the greater cerebrovascular responses, we also observed more modest systemic responses (lower HR, MAP, CO) and lower self-reported ratings of perceived exertion (p<0.001) in R30 compared to other protocols. Acute increases in MCACVCi and ICA blood flow observed in R30 (despite the lower perceived effort) may suggest that rhythmic HGE at low-moderate intensities can be a tolerable prescription for inducing exercise-related cerebrovascular adaptations (i.e., improved cerebral perfusion) in populations that may require adapted physical activity.

physiology↗

bioRxiv2021

HIF-dependent Neuropeptide Y Receptor Y1 and Y5 expression sensitizes hypoxic cells to NPY stimulation

Neuropeptide Y (NPY) is an abundant neurohormone in the central and peripheral nervous system involved in feeding behavior, energy balance, nociception, and anxiety. Several NPY receptor (NPYR) subtypes display elevated expression in many cancers including in breast cancer where this is exploited for imaging and diagnosis. Here, we show that NPY1R and NPY5R mRNA abundance is induced by hypoxia in a Hypoxia Inducible Factor (HIF)-dependent manner in breast cancer cell lines MCF7 and MDA-MB-231. The HIFs bind to several genomic regions upstream of the NPY1R and NPY5R transcription start sites. The MAPK/ERK pathway is activated more rapidly upon NPY5R stimulation in hypoxic cells compared to normoxic cells. This pathway requires IGF1R activity in normoxia, but not in hypoxic cells where they display resistance to the radiosensitizer and IGF1R inhibitor AG1024. Hypoxic cells proliferate and migrate more when stimulated with NPY relative to normoxic cells, with a more robust response observed with a Y5-specific agonist. Our data suggest that hypoxia induced NPYRs render hypoxic cells more sensitive to NPY stimulation. Considering that breast tissue receives a constant supply of NPY, and hypoxia is a common feature of the tumor microenvironment, breast tumors are the perfect storm for hyperactive NPYR. This study not only highlights a new relationship between the HIFs and NPYR expression and activity, but may inform the use of chemotherapeutics targeting NPYRs and hypoxic cells.

molecular biology↗

bioRxiv2021

Protocol-Dependence of Middle Cerebral Artery Dilation to Modest Hypercapnia

There is a need for improved understanding of how different cerebrovascular reactivity (CVR) protocols affect vascular cross-sectional area (CSA) when measures of vascular CSA are not feasible. In human participants, we delivered ~{+/-}4mmHg end-tidal partial pressure of CO2 (PETCO2) relative to baseline through controlled delivery, and measured changes in middle cerebral artery (MCA) cross-sectional area (CSA; magnetic resonance imaging (7 Tesla MRI)), blood velocity (transcranial Doppler and Phase contrast MRI), and calculated CVR based on steady-state versus a ramp protocol during two protocols: a 3-minute steady-state (+4mmHg PETCO2) and a ramp (delta of -3 to +4mmHg of PETCO2). We observed that 1) the MCA did not dilate during the ramp protocol, but did dilate during steady-state hypercapnia, and 2) MCA blood velocity CVR was similar between ramp and steady-state hypercapnia protocols, although calculated MCA blood flow CVR was greater during steady-state hypercapnia than during ramp, the discrepancy due to MCA CSA changes during steady-state hypercapnia. Due to the ability to achieve similar levels of MCA blood velocity CVR as steady-state hypercapnia, the lack of change in MCA cross-sectional area, and the minimal expected change in blood pressure, we propose that a ramp model, across a delta of ~-3 to +4mmHg PETCO2, may provide one alternative approach to collecting CVR measures in young adults with TCD when CSA measures are not feasible.

physiology↗