Spinal Cord Swelling and Alterations in Hydrostatic Pressure after Acute Injury

Each year, over 12,000 Americans are paralyzed after suffering an acute traumatic spinal cord injury (SCI). Unfortunately, current treatment options for acute SCI are extremely limited. Damage to the bone or vertebrae that make up the spine can cause compression to the spinal cord or the nerve roots exiting the spinal cord. In such cases, surgery to decompress the spinal cord is often performed in order to remove bone fragments and relieve pressure on the cord. It seems intuitive that surgically relieving this bony compression of the traumatically injured cord in an expeditious manner would improve neurologic function. However, it has been surprisingly challenging to demonstrate the beneficial effects of early surgical decompression in clinical studies of human SCI. One potential reason for this is the swelling and pressure increase within the spinal cord that occurs even after surgical decompression.

Our data using a large animal model of SCI suggests that such post-injury swelling causes the cord to expand inside the fluid filled space around the spinal cord, ultimately causing it to be compressed against its surrounding protective membrane called the dura matter. Such swelling may thus result in the cord being subjected to significant pressure due to constriction by its surrounding dura mater, despite the fact that the offending bony compression has been surgically removed. Although the impact of this dural compression on blood supply to the spinal cord has not been systematically evaluated, it is reasonable to speculate that increasing the pressure on the spinal cord in this fashion would result in reduced blood supply and jeopardize the injured spinal cord that is already vulnerable to further insults. When oxygen and glucose delivery become insufficient to meet the metabolic demands of the injured cord, further death of nerves within the spinal cord will occur.

This research proposal is focused on this severe (and poorly understood) swelling of the human spinal cord that is typically observed after traumatic injury. Characterizing the physiologic and biological downstream effects of this phenomenon and determining how they can be mitigated to reduce secondary injury will guide the optimal clinical management for these acute SCI patients. To interrogate this phenomenon, we will utilize our recently developed large animal (porcine) model of SCI. This shares similar size and anatomic characteristics to the human spinal cord, thus allowing us to model the swelling and compression against the dura mater that is observed after human injury. We have developed the techniques for placing monitoring probes directly into the spinal cord in order to measure pressure, spinal cord blood flow, and metabolic responses. We will utilize all of these techniques to answer the following fundamental questions: After surgical decompression, is the commonly observed spinal cord swelling associated with increased pressure within the cord that is made worse when it expands against the dura mater? Is this swelling associated with impaired blood perfusion and ischemia (oxygen-glucose deprivation)? Can these insults be mitigated by a routine surgical procedure where the dura is cut open and a patch is sewn in to expand the space around the spinal cord?

We will also use our model to investigate a technique called the 'Pressure Reactivity Index' that has been increasingly used in traumatic brain injury to establish the optimal blood pressure management in such patients. In traumatic brain injury, because the brain swells against the surrounding dura and skull, there can be significant pressure increases within the brain that affect its blood supply. Using the Pressure Reactivity Index to determine how to best augment blood supply to the brain has been shown to improve outcomes. This approach, however, has not been evaluated in spinal cord injury. We will establish whether this can be determined in acute SCI, and whether optimizing blood pressure with this Index can improve blood supply and metabolic responses after injury.

Our study is therefore focused on informing and improving current clinical practice for acute SCI. Our findings could be translated 'from bench to bedside' to help clinicians better understand how to manage acute SCI patients both surgically (by opening the dura mater and expanding the space for the spinal cord to swell into) and medically (by defining the best blood pressure management for supplying an adequate blood supply to the injured cord). Optimizing the clinical management of patients with acute SCI will promote improved neurologic function.