Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo

Atsuo Mori, Toshihiko Ueda, Tsukasa Nakamichi, Mikito Yasudo, Ryo Aeba, Hiroshi Odaguchi, Atsuhiro Mitsumaru, Tsutomu Ito, Ryohei Yozu, Atsuo Koto, Shiaki Kawada

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 α-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.

Original languageEnglish
Pages (from-to)1057-1062
Number of pages6
JournalAnnals of Thoracic Surgery
Volume63
Issue number4
DOIs
Publication statusPublished - 1997 Apr

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Glutamic Acid
Spinal Cord
Ischemia
Neurons
Paraplegia
Nervous System
Paraparesis
Excitatory Amino Acid Antagonists
Physiological Stress
Kainic Acid
Poisons
Necrosis
Rabbits
Control Groups

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Mori, A., Ueda, T., Nakamichi, T., Yasudo, M., Aeba, R., Odaguchi, H., ... Kawada, S. (1997). Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo. Annals of Thoracic Surgery, 63(4), 1057-1062. https://doi.org/10.1016/S0003-4975(96)01388-4

Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo. / Mori, Atsuo; Ueda, Toshihiko; Nakamichi, Tsukasa; Yasudo, Mikito; Aeba, Ryo; Odaguchi, Hiroshi; Mitsumaru, Atsuhiro; Ito, Tsutomu; Yozu, Ryohei; Koto, Atsuo; Kawada, Shiaki.

In: Annals of Thoracic Surgery, Vol. 63, No. 4, 04.1997, p. 1057-1062.

Research output: Contribution to journalArticle

Mori, A, Ueda, T, Nakamichi, T, Yasudo, M, Aeba, R, Odaguchi, H, Mitsumaru, A, Ito, T, Yozu, R, Koto, A & Kawada, S 1997, 'Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo', Annals of Thoracic Surgery, vol. 63, no. 4, pp. 1057-1062. https://doi.org/10.1016/S0003-4975(96)01388-4
Mori, Atsuo ; Ueda, Toshihiko ; Nakamichi, Tsukasa ; Yasudo, Mikito ; Aeba, Ryo ; Odaguchi, Hiroshi ; Mitsumaru, Atsuhiro ; Ito, Tsutomu ; Yozu, Ryohei ; Koto, Atsuo ; Kawada, Shiaki. / Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo. In: Annals of Thoracic Surgery. 1997 ; Vol. 63, No. 4. pp. 1057-1062.
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T1 - Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo

AU - Mori, Atsuo

AU - Ueda, Toshihiko

AU - Nakamichi, Tsukasa

AU - Yasudo, Mikito

AU - Aeba, Ryo

AU - Odaguchi, Hiroshi

AU - Mitsumaru, Atsuhiro

AU - Ito, Tsutomu

AU - Yozu, Ryohei

AU - Koto, Atsuo

AU - Kawada, Shiaki

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N2 - 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 α-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.

AB - 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 α-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.

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