Spinal Cord Injury
Spinal cord injury (SCI) is a debilitating and life-altering condition. The initial physical insult to the spinal cord (primary injury) is followed by a cascade of secondary cellular events that act to exacerbate the initial detriment (secondary injury). Progressive damage includes breakdown of the blood-spinal cord barrier (BSCB), formation of a glial scar, accumulation of edema, hemorrhage, inflammation and eventual cell death. Specifically, edema begins during the acute phase after injury and spreads rostrally and caudally from the injury epicenter. Edema can be due to both vasogenic and cytotoxic mechanisms. Injury severity and patient outcome correlate well with the development and alleviation of edema and cord pressure at the injury site. While the damage due to the initial injury is not preventable, the resulting secondary injury due to edema may be averted or even reversed to improve neurological outcome. However, to date there is no widely accepted and effective treatment for edema following SCI.
Movement of water across membranes is facilitated by the aquaporin family of membrane-bound water channels. Aquaporin-4 (AQP4) is the most abundantly expressed water channel in the spinal cord, located at astrocytic endfeet around vasculature, the glia limitans and the central canal. Local expression at the interface between fluid and tissue allows AQP4 channels to play a central role in the regulation of water under normal conditions and following trauma to the spinal cord. Decreases in AQP4 protein levels have been observed in the acute period after SCI followed by chronic elevations in expression. Studies in AQP4-deficient mice reveal a profound role for AQP4 in water accumulation and removal following SCI. In our laboratory, we hope to further understand the regulation and role of AQP4 water channels following SCI.
We have also developed a direct method to treat SCI-associated edema for the first time. We have collaborated with the Bioengineering department at UC Riverside to create a therapeutic device that can be placed onto the spinal cord following injury. This device allows for controlled reduction in tissue water content (and thus resolution of edema) through the creation of an osmotic pressure gradient, without creating further injury to the underlying tissue. The goal of this project is to effectively remove edema fluid from the spinal cord, reduce cord pressure and restore tissue integrity after SCI. We are currently carrying out these studies with grant support from the Craig H. Neilsen Foundation (www.chnfoundation.org).