Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo.
BACKGROUND
Paraplegia remains a serious complication of thoracoabdominal aortic operations. However, despite growing in vitro evidence, it has been difficult to demonstrate glutamate neurotoxicity in vivo because of the reuptake activity that occurs. We hypothesized that glutamate can be toxic to the spinal cord under metabolic stress.


METHODS
Infrarenal aortic isolation was performed in New Zealand white rabbits. Group A animals (n = 7) then received a segmental infusion of glutamate (50 mmol/L) for 5 minutes. Group B animals (n = 7) received saline as a negative control. Group C animals (n = 6) were pretreated with a segmental infusion of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (4 mg/kg), a competitive alpha-amino-3-hydroxy-5-methylisoazole-4-propionic acid/kainate antagonist, followed by the segmental infusion of glutamate (30 mmol/L) for 4 minutes. Group D animals (n = 6) received the vehicle agents only, followed by the same glutamate infusion (30 mmol/L) as in group C as a control for group C. Neurologic status was assessed at 12, 24, and 48 hours after operation and scored using the Tarlov system.


RESULTS
Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B animals recovered fully. Group C animals had better neurologic function than group D animals (p = 0.0039).


CONCLUSIONS
Exogenous glutamate can have detrimental effects on spinal cord neurons during a brief period of ischemia. This model may be useful for the purpose of assaying a glutamate receptor antagonist in vivo.
Mori
A
A
Department of Cardiovascular Surgery, Keio University, Shinjuku, Tokyo, Japan.
Ueda
T
T
Nakamichi
T
T
Yasudo
M
M
Aeba
R
R
Odaguchi
H
H
Mitsumaru
A
A
Ito
T
T
Yozu
R
R
Koto
A
A
Kawada
S
S
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D007511:Ischemia / Q000150:complications*; D009474:Neurons / Q000187:drug effects*; D010264:Paraplegia / Q000139:chemically induced*; D010291:Paresis / Q000139:chemically induced*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid