Abstract
BACKGROUND: Recent discoveries focused on the role of cerebrospinal fluid (CSF) in metabolite clearance have initiated intense research on CSF circulation and outflow pathways. These studies have focused on the cranial subarachnoid space, whereas spinal outflow has been relatively less investigated. Moreover, most studies have been performed on rodent models, which allows thorough anatomical investigation, whereas evidence from humans has been generated primarily from in vivo neuroimaging techniques. In this paper, we introduce an anatomical specimen-based preparation for studying spinal CSF outflow in humans and present preliminary results from our initial studies. METHODS: Unfixed anatomical specimens of the thoracolumbar spinal dural sac along with the spinal nerves were obtained from cadavers. Experiments involving low-pressure infusion of contrast medium (barium sulfate) into the spinal subarachnoid space with video recording of contrast spread were performed. After fixation, contrast agent distribution of the samples was assessed via histological and radiological analyses including 3D X-ray microscopy. RESULTS: Five human anatomical specimens of the dural sac were assessed. Filling of spaces extending to the spinal dura (arachnoid granulations, cuffs around the proximal spinal nerves) and unrestricted outflow from postganglionic spinal nerve cross-sections were both observed. Histological and radiological results confirmed the presence of contrast around the spinal nerve fascicles under the perineurium, in the arachnoid granulations and within the lumens of vessels within the dura or in the surrounding epidural adipose tissue. CONCLUSIONS: The described model makes it possible to examine CSF outflow routes from the human spinal subarachnoid space. The methodology is reproducible, feasible, and does not require specialized equipment. Preliminary results have revealed two potential CSF outflow pathways that have been previously observed in animal models: along the spinal nerves and to the epidural tissue and vessels.