Abstract
Recent advancements have been made toward understanding the diagnostic and therapeutic potential of cerebrospinal fluid (CSF) and related hydrodynamics. Increased understanding of CSF dynamics may lead to improved detection of central nervous system (CNS) diseases and optimized delivery of CSF based CNS therapeutics, with many proposed therapeutics hoping to successfully treat or cure debilitating neurological conditions. Before significant strides can be made toward the research and development of interventions designed for human use, additional research must be carried out with representative subjects such as non-human primates (NHP). This study presents a geometric and hydrodynamic characterization of CSF in eight cynomolgus monkeys (Macaca fascicularis) at baseline and two-week follow-up.Results showed that CSF flow along the entire spine was laminar with a Reynolds number ranging up to 80 and average Womersley number ranging from 4.1–7.7. Maximum CSF flow rate occurred ~25 mm caudal to the foramen magnum. Peak CSF flow rate ranged from 0.3–0.6 ml/s at the C3-C4 level. Geometric analysis indicated that average intrathecal CSF volume below the foramen magnum was 7.4 ml. The average surface area of the spinal cord and dura was 44.7 and 66.7 cm2 respectively. Subarachnoid space cross-sectional area and hydraulic diameter ranged from 7–75 mm2 and 2–3.7 mm, respectively. Stroke volume had the greatest value of 0.14 ml at an axial location corresponding to C3-C4.
Highlights
Cerebrospinal fluid (CSF) is a clear, colorless fluid with water-like mechanical properties that bathes the entire brain and spinal cord
Peak CSF flow rate ranged from 0.3–0.6 ml/s at the C3-C4 level
CSF flow was laminar in all non-human primates (NHP) with the greatest degree of CSF motion observed in the cervical spine
Summary
Cerebrospinal fluid (CSF) is a clear, colorless fluid with water-like mechanical properties that bathes the entire brain and spinal cord. Recent advances have been made toward understanding the diagnostic and therapeutic potential of CSF and related hydrodynamics. Increased understanding of CSF dynamics may lead to improved detection of CNS diseases, development of CSF system-based intrathecal drug delivery, and improved treatment of debilitating neurological conditions. The importance of CSF dynamics has been investigated in several CNS conditions including syringomyelia [6] Alzheimer’s disease [7], Chiari malformation [8], and hydrocephalus [9]. Researchers have applied computational fluid dynamics modeling approaches to understand how CSF dynamics related parameters could relate to CNS disease states and intrathecal drug delivery [10,11,12,13,14]. Relatively little information is known regarding CSF geometry and hydrodynamics in NHPs
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