Numerical Models of Spinal Cord Trauma: The Effect of Cerebrospinal Fluid Pressure and Epidural Fat on the Results

The cerebrospinal fluid (CSF) is contained in the brain ventricles and the cranial and spinal subarachnoid spaces. The mean CSF volume is 150 ml, with 25 ml in the ventricles and 125 ml in subarachnoid spaces. CSF is predominantly, but not exclusively, secreted by the choroid plexuses. Brain interstitial fluid, ependyma and capillaries may also play a poorly defined role in CSF secretion. CSF circulation from sites of secretion to sites of absorption largely depends on the arterial pulse wave. Additional factors such as respiratory waves, the subject's posture, jugular venous pressure and physical effort also modulate CSF flow dynamics and pressure. Cranial and spinal arachnoid villi have been considered for a long time to be the predominant sites of CSF absorption into the venous outflow system. Experimental data suggest that cranial and spinal nerve sheaths, the cribriform plate and the adventitia of cerebral arteries constitute substantial pathways of CSF drainage into the lymphatic outflow system. CSF is renewed about four times every 24 hours. Reduction of the CSF turnover rate during ageing leads to accumulation of catabolites in the brain and CSF that are also observed in certain neurodegenerative diseases. The CSF space is a dynamic pressure system. CSF pressure determines intracranial pressure with physiological values ranging between 3 and 4 mmHg before the age of one year, and between 10 and 15 mmHg in adults. Apart from its function of hydromechanical protection of the central nervous system, CSF also plays a prominent role in brain development and regulation of brain interstitial fluid homeostasis, which influences neuronal functioning. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho-associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.

In vivo, tissue-level, mechanical thresholds for axonal injury were determined by comparing morphological injury and electrophysiological impairment to estimated tissue strain in an in vivo model of axonal injury. Axonal injury was produced by dynamically stretching the right optic nerve of an adult male guinea pig to one of seven levels of ocular displacement (Nlevel = 10; Ntotal = 70). Morphological injury was detected with neurofilament immunohistochemical staining (NF68, SM132). Simultaneously, functional injury was determined by the magnitude of the latency shift of the N35 peak of the visual evoked potentials (VEPs) recorded before and after stretch. A companion set of in situ experiments (Nlevel = 5) was used to determine the empirical relationship between the applied ocular displacement and the magnitude of optic nerve stretch. Logistic regression analysis, combined with sensitivity and specificity measures and receiver operating characteristic (ROC) curves were used to predict strain thresholds for axonal injury. From this analysis, we determined three Lagrangian strain-based thresholds for morphological damage to white matter. The liberal threshold, intended to minimize the detection of false positives, was a strain of 0.34, and the conservative threshold strain that minimized the false negative rate was 0.14. The optimal threshold strain criterion that balanced the specificity and sensitivity measures was 0.21. Similar comparisons for electrophysiological impairment produced liberal, conservative, and optimal strain thresholds of 0.28, 0.13, and 0.18, respectively. With these threshold data, it is now possible to predict more accurately the conditions that cause axonal injury in human white matter.