Exogenous aspartate neurotoxicity in the spinal cord under metabolic stress in vivo.
BACKGROUND
Considerable evidence exists that neurotoxicity of excitatory amino acids is related to the neuronal injury, including paraplegia. However, little is known about aspartate neurotoxicity in the spinal cord in vivo. We evaluated the detrimental effects of exogenous aspartate on spinal cord neurons under metabolic stress.


METHODS
New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate 50 mmol/L) infusion for 10 minutes. Group B animals (n = 7) received saline as a negative control. Group C animals (n = 5) received segmental aspartate 100 mmol/L) infusion for 5 minutes. Group D animals (n = 7) were pretreated with segmental infusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (MK-801) (6 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist for 1 minute, followed by segmental infusion of aspartate (50 mmol/L) for 9 minutes. Group E animals (n = 7) received vehicle only, followed by aspartate (50 mmol/L) infusion as a control of group D. Neurologic status was assessed at 12, 24, and 48 hours after operation using the Tarlov score.


RESULTS
Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals recovered fully. Group D animals showed significantly better neurologic function (p = 0.0007) compared with group E animals that exhibited paraplegia or paraparesis.


CONCLUSIONS
Exogenous aspartate can have detrimental effects on spinal cord neurons under metabolic stress. This model may be useful in assaying neuronal injury mediated by NMDA receptor in vivo.
Cho
Y
Y
Department of Cardiovascular Surgery, Keio University, Tokyo, Japan. noricho@aol.com
Ueda
T
T
Mori
A
A
Nakamichi
T
T
Shimizu
H
H
Inoue
Y
Y
Kawada
S
S
D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects; D010264:Paraplegia / Q000139:chemically induced; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects*; D013312:Stress, Physiological / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D016291:Dizocilpine Maleate