Srdjan Cirovic

Aim: Chiari malformation and syringomyelia are disorders of cerebrospinal fluid (CSF) dynamics, yet translation of mechanistic insights into patient care is limited by the low prevalence and heterogeneity of human disease, and by methodological constraints of in-vivo CSF measurements. In Cavalier King Charles Spaniels (CKCS), these conditions are highly prevalent and represent a clinically relevant companion animal model. However, existing canine CSF flow studies rely largely on phase-contrast magnetic resonance imaging (MRI) metrics that incompletely characterize three-dimensional flow. This study aimed to develop a computational fluid dynamics (CFD) framework to characterise CSF flow dynamics in CKCS, providing a translational approach for investigating CSF dynamics in both veterinary and human cases.

Methods: Retrospective MRI data from nine clinically normal CKCS were used to construct subject-specific craniospinal CSF geometries. CFD simulations yielded cardiac-driven oscillatory CSF motion under physiologically plausible boundary conditions, incorporating spinal compliance and zero net flow per cardiac cycle to characterize velocities and pressures.

Results: Simulations revealed pulsatile, laminar CSF flow with pronounced regional heterogeneity, dominant subarachnoid space (SAS) transport, complex flow patterns within the cerebral aqueduct, and a cycle-dependent pressure difference between the central canal and SAS with marked sensitivity to anatomical location and downstream spinal geometry.

Conclusion: These findings demonstrate that local anatomy strongly influences measured CSF velocities, limiting the translational reliability of isolated in vivo measurements while supporting CFD as a more robust framework for clinically meaningful interpretation. Establishing these baseline craniospinal flow characteristics provides a necessary reference for interpreting clinical CSF measurements and for extending computational analyses to dogs with Chiari-like malformation and syringomyelia.

Many cells respond to changes in concentration of extracellular molecules (chemotaxis) by directing migration towards increased concentration of molecules such as food or signaling molecules, or away from toxins. Similarly, some cells respond to extracellular electric fields by migrating towards cathode or anode (electrotaxis). However, only motile bacteria are known to respond to extracellular ion gradients (ionotaxis), with no similar reports in mammalian cells.
We used microfluidic gradient chips to examine the migration of human macrophages in concentration gradients of sodium, potassium and chloride.
All three ion gradients significantly directed motion in the direction of the gradient compared to cell migration at constant concentration. Macrophages showed significant migration towards higher concentrations of cations. Gradients as low as ± 0.025% over ambient ion concentration could be sensed. The results suggest that macrophages use small changes in extracellular K + and Na+, to identify injury sites, given that increases in local K
in the body would signify cell rupture.
We also considered the implications of this effect for the phenomenon of electrotaxis. Electric fields induce dipoles at the cell surface, aligned with the field. If these interact with extracellular ions, they will generate local ion gradients across the cell, which the cell can then follow. Hence it is the induced gradient, not the electric field, which the cell interacts with.
This work suggests that local variation in ion concentrations may be a previously unexplored mechanism for cellular communication with ramifications for cell function, developmental biology and cancer.

The exact pathogenesis of syringomyelia is unknown. Epidural venous distention during raised intrathoracic pressure (Valsalva) may cause impulsive movement of fluid ( "slosh ") within the syrinx. Such a slosh mechanism is a proposed cause of syrinx dissection into spinal cord parenchyma resulting in craniocaudal propagation of the cavity. We sought to test the "slosh " hypothesis by epidural excitation of CSF pulse in a computer model of canine syringomyelia. Our previously developed canine syringomyelia computer model was modified to include an epidural pressure pulse. Simulations were run for: cord free of cavities; cord with small syringes at different locations; and cord with a syrinx that was progressively expanding caudally. If small syringes are present, there are peaks of stress at those locations. This effect is most pronounced at the locations at which syringes initially form. When a syrinx is expanding caudally, the peak stress is typically at the caudal end of the syrinx. However, when the syrinx reaches the lumbar region; the stress becomes moderate. The findings support the "slosh " hypothesis, suggesting that small cervical syringes may propagate caudally. However, when the syrinx is large, there is less focal stress, which may explain why a syrinx can rapidly expand but then remain unchanged in shape over years.

Background Shockwave treatment is increasingly used for plantar fasciitis and Achilles tendinopathy. To be effective it is believed that high pressure must be achieved in the tissues. We report on the first human cadaveric experiments to characterize pressure from radial shockwave therapy (rSWT) for plantar fasciitis. Methods The pressure from rSWT was measured in two cadaveric feet using a needle hydrophone. Maximal pressure and energy flux were calculated from the measurements. Results The pressure persisted longer than supposed, for up to 400 μs. The peak negative pressure was up to two Mega Pascal. The predicted energy in the tissue strongly depended on the time interval used in calculations. Conclusions The measured pressure may be sufficiently high to cause cavitation in the tissue, which is one of the proposed healing mechanisms associated with rSWT. The results suggest that the energy is imparted to the tissues for much longer than previously thought.