What drives fluid flow in and around the spinal cord?


There is mounting evidence that disruption to CSF circulation and CSF/interstitial fluid exchange is likely to contribute to a number of CNS diseases including syringomyelia. However, the physiological factors that govern CSF flow in the subarachnoid space (SAS) and fluid transport in the spinal cord are poorly understood.


The aims of this study were to determine the effects of heart rate, blood pressure and respiration on the flow of fluid in the subarachnoid space, as well as into and out of the spinal interstitium.


In Sprague Dawley rats, physiological parameters were carefully manipulated such that the effects of free breathing (negative intrathoracic pressure), mechanical ventilation (positive intrathoracic pressure), tachy/bradycardia, as well as hyper/hypotension were separately investigated. To investigate spinal CSF hydrodynamics, in vivo near infrared imaging of intracisternally infused indocyanine green was performed. Spinal fluid inflow at a microscopic level was characterised by in vivo twophoton intravital microscopic imaging of fluorescent ovalbumin and microspheres injected into the SAS. Complementary quantitative data was obtained in ex vivo epifluorescence studies employing ovalbumin. To assess fluid outflow, ovalbumin was injected into the cervicothoracic spinal grey or white matter.


Compared to controls, free-breathing animals had significantly greater flow of CSF in the SAS as well as inflow of tracer into the spinal cord. Hypertension and tachycardia had no significant effect on SAS CSF flow. Hypertension resulted in reduced tracer inflow, whereas increased tracer influx was observed with tachycardia. Both tachycardia and hypertension stimulated tracer efflux, but respiration was not found to affect spinal interstitial clearance.


Intrathoracic pressure has a significant effect on spinal subarachnoid CSF flow and parenchymal fluid ingress. Cardiovascular pulsations play a smaller role in SAS hydrodynamics but have profound effects on spinal interstitial fluid homeostasis.