Large naturally-produced electric currents and voltage traverse damaged mammalian spinal cord

Mahvash Zuberi,Peishan Liu-Snyder,Aeraj ul Haque,Richard B Borgens,David M Porterfield

doi:10.1186/1754-1611-2-17

Abstract

BackgroundImmediately after damage to the nervous system, a cascade of physical, physiological, and anatomical events lead to the collapse of neuronal function and often death. This progression of injury processes is called "secondary injury." In the spinal cord and brain, this loss in function and anatomy is largely irreversible, except at the earliest stages. We investigated the most ignored and earliest component of secondary injury. Large bioelectric currents immediately enter damaged cells and tissues of guinea pig spinal cords. The driving force behind these currents is the potential difference of adjacent intact cell membranes. For perhaps days, it is the biophysical events caused by trauma that predominate in the early biology of neurotrauma.ResultsAn enormous (≤ mA/cm2) bioelectric current transverses the site of injury to the mammalian spinal cord. This endogenous current declines with time and with distance from the local site of injury but eventually maintains a much lower but stable value (< 50 μA/cm2).The calcium component of this net current, about 2.0 pmoles/cm2/sec entering the site of damage for a minimum of an hour, is significant. Curiously, injury currents entering the ventral portion of the spinal cord may be as high as 10 fold greater than those entering the dorsal surface, and there is little difference in the magnitude of currents associated with crush injuries compared to cord transection. Physiological measurements were performed with non-invasive sensors: one and two-dimensional extracellular vibrating electrodes in real time. The calcium measurement was performed with a self-referencing calcium selective electrode.ConclusionThe enormous bioelectric current, carried in part by free calcium, is the major initiator of secondary injury processes and causes significant damage after breach of the membranes of vulnerable cells adjacent to the injury site. The large intra-cellular voltages, polarized along the length of axons in particular, are believed to be associated with zones of organelle death, distortion, and asymmetry observed in acutely injured nerve fibers. These data enlarge our understanding of secondary mechanisms and provide new ways to consider interfering with this catabolic and progressive loss of tissue.

Highlights

After damage to the nervous system, a cascade of physical, physiological, and anatomical events lead to the collapse of neuronal function and often death
The biology/pathology forming the basis for secondary injury in the mammalian CNS includes – but is not limited to – particular biochemistries such as: the formation of reactive oxygen species and the initiation of lipid peroxidation of the inner membrane which begins immediately after mechanical damage to CNS cells [2,3] the formation of endogenous toxins that accumulate within damaged neurons and their processes [3]; the loss of myelin and the associated collapse of electrophysiological conduction [1,4]; and the initiation of both apopotosis and progressive necrosis by chemically-mediated events
Note that the current density at distance of up to 2 mm from injury site is much higher. If this plot were to be extended, it would touch the x-axis "cms" away from the injury site. This implies that the injury current field is much larger than expected and might explain the extent to which a focal injury can propagate in distance and time

Summary

Introduction

After damage to the nervous system, a cascade of physical, physiological, and anatomical events lead to the collapse of neuronal function and often death. The biology/pathology forming the basis for secondary injury in the mammalian CNS includes – but is not limited to – particular biochemistries such as: the formation of reactive oxygen species (so-called free radicals) and the initiation of lipid peroxidation of the inner membrane which begins immediately after mechanical damage to CNS cells [2,3] the formation of endogenous toxins that accumulate within damaged neurons and their processes [3]; the loss of myelin and the associated collapse of electrophysiological conduction [1,4]; and the initiation of both apopotosis and progressive necrosis by chemically-mediated events These are the two main forms of cell death in adult animals, and each plays a role in the demise of CNS parenchyma after mechanical damage [3,5]

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