Time Dependence of N‐Acetyl‐Aspartate, Lactate, and Pyruvate Concentrations Following Spinal Cord Injury

Abstract

The time dependence of N‐acetyl‐aspartate (NAA) concentrations relative to lactate and pyruvate in the injured rat spinal cord was investigated. Segments of spinal cord from regions rostral, caudal, and at the epicenter of the injury were analyzed. NAA concentrations were determined by gas chromatography‐mass spectrometry and lactate and pyruvate concentrations were determined by UV spectroscopy at 20 min, 60 min, 2 h, 8 h, 24 h, 3 days, and 1 week after injury. NAA levels fell most significantly at the epicenter of the injury, reaching 30% of basal levels within 24 h. In all segments, lactate levels increased significantly shortly after injury, peaking at two to five times normal basal levels between 20 and 60 min after injury. Rostral and caudal to the injury site, lactate elevations and NAA reductions were less dramatic. Pyruvate concentrations were not significantly altered in any of the sections after injury. The temporal and spatial relationships of NAA and lactate changes indicated that ischemic conditions due to injury in the upper thoracic rat spinal cord were distributed asymmetrically. Acute ischemia was more severe caudal to the injury site, and NAA concentrations were more severely impaired in the rostral direction. The results suggest that the extent of neuronal degeneration due to spinal cord injury does not correlate directly with acute ischemic severity as measured by the lactate/pyruvate ratio, and may be more closely related to secondary changes in the neuronal environment.

Neuronal and Axonal Degeneration in Experimental Spinal Cord Injury: In Vivo Proton Magnetic Resonance Spectroscopy and Histology

“…This NAA reduction is consistent with previous results that found that in a similar animal spinal cord injury model NAA levels in rostral and epicenter regions declined at 7 days PI as measured by gas chromatography-mass spectrometry (Falconer et al, 1996). Moreover, in our study, the results of immunohistochemistry clearly showed that neuronal loss in gray matter was accompanied by a loss of phosphorylated neurofilament heavy chain and myelin basic protein in dorsal, lateral, and ventral white-matter regions, which indicated axonal loss and demyelination in these regions.…”

“…The pathobiology of SCI is characterized by the primary mechanical insult followed by activation of a delayed secondary cascade of biochemical events that ultimately causes progressive tissue degeneration, including neuronal cell death, axonal degeneration, and cavitation in the spinal cord (Baptiste and Fehlings, 2006). The pathobiological changes of primary and secondary damage in SCI can be monitored by quantifying changes in metabolites such as N-acetyl aspartate (NAA), lactate, and pyruvate (Falconer et al, 1996).…”

In vivo serial diffusion tensor imaging of experimental spinal cord injury

“…It is interesting to note that Falconer et al (1996) have also observed the levels of N-acetyl aspartate, molecules that are found exclusively in the neuronal and neuronal processes, are more severely impaired in sections rostrals to the site of injury relative to the caudal direction. These authors attributed this asymmetric behavior to the more compromised blood flow in the rostral sections relative to the caudal section.…”

Metabolite Profiles Correlate Closely with Neurobehavioral Function in Experimental Spinal Cord Injury in Rats

“…NAAG has been shown to be an important marker of neuronal viability. NAA levels are closely associated with neuronal function [31], and NAA concentration in spinal cord was decreased rapidly after the spinal cord injury in rats [32]. Decreased NAA levels have also been reported in various neurodegenerative diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis and Parkinson’s disease [33]–[35].…”