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Osborne, P. B.

Publications and source records attributed to Osborne, P. B..

2 recordsLinked to original sources

A multi-scale vascular atlas of blood vessels within the urinary bladder of male and female mice

The vascular supply of the urinary bladder is embedded within a highly dynamic environment that includes alternating cycles of regional compression or stretching during bladder filling, sustained continence and voiding. These place unique demands on the vasculature to maintain tissue perfusion, fluid homeostasis and immune surveillance. Understanding this vascular regulation is also highly relevant to defining mechanisms of organ reperfusion following pelvic surgery, pelvic venous insufficiency, and the impacts of diabetes and ischemia on urinary function. There is limited anatomical knowledge on the organization of this vascular network, so we aimed to determine if there are stereotypical features associated with the mouse urinary bladder. We applied advanced microscopy and anatomical visualization methods to samples of the entire bladder viewed as a whole mount, including intravital tomato lectin labeling of the arterial vasculature, multi-channel immunofluorescence, tissue clearing, light-sheet and confocal microscopy. We developed a comprehensive multi-scale 3D anatomical map of the stereotypical arterial and venous networks associated with the mouse urinary bladder in both sexes, showing that the primary features of this network are established by the early postnatal period, prior to maturation of voiding and continence reflexes. These outcomes provide the foundation for probing mechanisms that underpin physiological and pathophysiological changes in the urinary bladder vascular network and a resource to guide more refined experimental perturbation, analysis and interpretation of vascular function/dysfunction in mouse models. This new knowledge on the structure of the urinary bladder vascular network will also benefit tissue engineering efforts seeking to restore or replace this organ.

physiology↗

A 3D atlas of sexually dimorphic lumbosacral motor neurons that control and integrate pelvic visceral and somatic functions in rats

The lumbosacral spinal motor system comprises somatic motor neurons (SMNs) that target striated muscle and visceral motor neurons (VMNs; autonomic preganglionic neurons) that target peripheral ganglia. The brain coordinates these pathways to mediate functions such as continence, voiding and sexual function by ensuring appropriate changes of organ state with striated muscle activity (e.g., sphincter opening, relevant postural changes). These spinal circuits are important therapeutic targets for bioelectronic medicine yet are poorly defined in comparison with limb SMNs. We aimed to define the structural features and relationships between SMNs and VMNs relevant to pelvic function in male and female rats, by building 3D maps of lumbosacral spinal cord. We achieved this by applying large-volume immunostaining (choline acetyltransferase), with tissue clearing and advanced whole mount microscopy (light sheet and ribbon scanning confocal microscopy). We identified VMNs specific to pelvic organ function by microinjecting cholera toxin (beta-subunit) into the major pelvic ganglia (MPG). These VMNS are primarily located in segments L1-L2 (dorsal commissural nucleus) and L6-S1 (intermediolateral nucleus). Unexpectedly, small groups of SMNs in the urethral rhabdosphincter, cremaster and levator ani motor pools also projected through the MPG. Motor neuron counts and analysis of dendritic fields detected sexual dimorphism in both SMNs and VMNs. Their colocation of dendritic bundles suggested a mechanism of coordinating activity. This study has provided the first multiscale 3D atlas of rat lumbosacral cord. This will be shared as a resource on an open science platform (sparc.science) to allow further exploration and modeling of network features and cellular morphology.

neuroscience↗