Changes of amino acid levels and aspartate distribution in the cervical spinal cord after traumatic spinal cord injury.
To evaluate the role of excitatory amino acids in secondary injury occurring after spinal cord trauma, several experimental studies focusing on the the changes of amino acid levels in the spinal cord have been performed to date. However, because of technical limitations, it has not been possible to correlate the local changes of excitatory amino acids with the total tissue levels of excitatory amino acids. To investigate the connection between the spread of injury and the excitatory amino acids, we assessed, the local changes of aspartate through novel experimental approaches like immunoreactivity via fluorescence microphotometry and histopathology while also analyzing the total tissue levels of amino acids via HPLC. These studies were performed using a model of incomplete cervical spinal cord injury in rats. Through this approach, we found that the levels of excitatory amino acids, such as glutamate and aspartate, began to decrease immediately after injury. No significant decrease was observed in the other amino acids. Similarly, local changes in aspartate in the spinal cord were observed using fluorescence microphotometry. The decrease in the anterior and posterior horns was rapid up to 15 min after injury, but, slowed thereafter, suggesting that a release of excitatory amino acids occurred at the site of primary injury almost immediately following injury. At 15-min post-injury large neurons within the injured cord appeared intact on histopathological analysis demonstrating that the alteration of excitatory amino acids occurs prior to histopathological change. Histopathological change in the white matter occurred more slowly than in the anterior and posterior horns, suggesting the spread of the lesion by secondary damage due to an autoclastic mechanism.
Watanabe
M
M
Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
Fujimura
Y
Y
Nakamura
M
M
Yato
Y
Y
Ohta
K
K
Okai
H
H
Ogawa
Y
Y
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*
D000596:Amino Acids; D001224:Aspartic Acid