The roads to mitochondrial dysfunction in a rat model of posttraumatic syringomyelia.

Zhiqiang Hu,Jian Tu

doi:10.1155/2015/831490

Zhiqiang Hu, Jian Tu

Open Access

https://doi.org/10.1155/2015/831490

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Abstract

The pathophysiology of posttraumatic syringomyelia is incompletely understood. We examined whether local ischemia occurs after spinal cord injury. If so, whether it causes neuronal mitochondrial dysfunction and depletion, and subsequent energy metabolism impairment results in cell starvation of energy and even cell death, contributing to the enlargement of the cavity. Local blood flow was measured in a rat model of posttraumatic syringomyelia that had received injections of quisqualic acid and kaolin. We found an 86 ± 11% reduction of local blood flow at C8 where a cyst formed at 6 weeks after syrinx induction procedure (P < 0.05), and no difference in blood flow rate between the laminectomy and intact controls. Electron microscopy confirmed irreversible neuronal mitochondrion depletion surrounding the cyst, but recoverable mitochondrial loses in laminectomy rats. Profound energy loss quantified in the spinal cord of syrinx animals, and less ATP and ADP decline observed in laminectomy rats. Our findings demonstrate that an excitotoxic injury induces local ischemia in the spinal cord and results in neuronal mitochondrial depletion, and profound ATP loss, contributing to syrinx enlargement. Ischemia did not occur following laminectomy induced trauma in which mitochondrial loss and decline in ATP were reversible. This confirms excitotoxic injury contributing to the pathology of posttraumatic syringomyelia.

Highlights

Following spinal cord injury, posttraumatic syringomyelia or cystic degeneration of the spinal cord develops in up to 30% of patients [1,2,3,4]
Spinal cord trauma triggers several pathophysiological events, including a massive release of glutamate, hyperactivation of N-methylD-aspartate receptors (NMDARs), and ischemia, which contribute to neuronal death and syrinx formation
Comparing to normal control and sham-operated rats, all rats developed a syrinx by 6 weeks after receiving combined intraparenchymal quisqualic acid and subarachnoid kaolin injection

Summary

Introduction

Posttraumatic syringomyelia or cystic degeneration of the spinal cord develops in up to 30% of patients [1,2,3,4] Most of these patients do not respond well to the current therapeutic options because the underlying mechanisms causing the formation and enlargement of such cavities are not fully understood [5]. Spinal cord trauma triggers several pathophysiological events, including a massive release of glutamate, hyperactivation of N-methylD-aspartate receptors (NMDARs), and ischemia, which contribute to neuronal death and syrinx formation. Structural changes due to hypoxia include mitochondrial rounding and moderate cell swelling. These changes are reversible if reoxygenation occurs. Rupture of plasma membrane brings about irreversible cellular injury and onset of necrotic cell death

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