Cerebrospinal fluid flow into the spinal cord in a rat model of extradural constriction: a network of perivascular pathways
thesisposted on 2022-03-29, 00:56 authored by Joel Anthony Berliner
The understanding of how cerebrospinal fluid (CSF) flows in and around central nervous system (CNS) tissue remains somewhat elusive. Historically, CSF was thought to flow around and within set structural boundaries of the CNS. More recently, a dynamic flow and exchange within neural tissue has been revealed. Of key interest is the role of perivascular pathways in fluid flow into and out of CNS tissue. In the brain, CSF has been reported to flow into tissue via periarterial pathways and out of tissue via perivenular pathways. The aim of this study was to determine whether the same flow pattern, or a notably different pattern, exists within the spinal cord. A C7 to T1 laminectomy was performed on 28 Sprague-Dawley rats. An extradural suture was tied around the spinal cord to obstruct CSF flow in 16 rats. The remaining animals were used as laminectomy-only controls. At 1 or 6 weeks post-surgery, animals were injected intracisternally with the fluorescent tracer Alexa-Fluor 647 ovalbumin and perfused 10 or 20 min after injection. Fixed and cryoprotected spinal segments were sectioned transversely and immunolabelled for smooth muscle actin and rat endothelial cell antigen. Fluorescent micrographs were taken and the distribution of tracer around arterioles, venules and capillaries was analysed. Intensity of gross grey matter and white matter tracer fluorescence showed that, at the 10 min time-point 6 weeks post-surgery, white matter in constriction animals (n = 5) had a significantly higher fluorescence intensity compared to the laminectomy-only animals (n = 3). Constriction animals in the same experimental group showed distribution of tracer around venules, arterioles and capillaries, whereas the control animals showed equivalent tracer distribution around arterioles and capillaries only. The results of this study suggest that an obstruction to CSF flow in the subarachnoid space may cause both increased fluid flow into the spinal cord and changes to the perivascular inflow pathways. Perivenular and pericapillary pathways, in addition to periarterial pathways, may act as an inflow route for CSF to the spinal cord tissue when the subarachnoid space is obstructed. Knowledge of the mechanics of normal and obstructed CSF physiology is necessary for understanding fluid accumulation pathologies, such as syringomyelia.