Abstract
We examined the neuroprotective effects of oren-gedoku-to (TJ15), a herbal medicine, after transient forebrain ischemia. Transient forebrain ischemia was induced by occlusion of both common carotid arteries for 15 min in C57BL/6 mice treated with TJ15. In the control ischemic group without TJ15 treatment, histologic examination of brain tissue collected seven days after reperfusion showed death of pyramidal cells in CA2-3 area of the hippocampus, unilaterally or bilaterally. In mice treated with oral TJ15 (845 mg/kg/day) for five weeks, the frequency of ischemic neuronal death was significantly lower. Immunohistochemistry for Cu/Zn-superoxide dismutase (Cu/Zn-SOD) showed strongly reactive astrocytes in the hippocampus of ischemic mice treated with TJ15. Damage to nerve cells by free radicals plays an important role in the induction of neuronal death by ischemia-reperfusion injury. Our results suggest that TJ15 protects against ischemic neuronal death by increasing the expression of Cu/Zn-SOD and suggest that oren-gedoku-to reduces the exposure of hippocampal neurons to oxidative stress.
Similar content being viewed by others
REFERENCES
Kabuto, H., Asanuma, M., Nishibayashi, S., Iida, M., and Ogawa, N. 1997. Chronic administration of Oren-gedoku-to (TJ15) inhibits ischemia-induced changes in brain indoleamine metabolism and muscarinic receptor binding in the Mongolian gerbil. Neurochem. Res. 22:33–36.
Haba, K., Ogawa, N., and Mori, A. 1990. The effects of sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960) on ischemiainduced changes of brain acetylcholine and monoamine levels in gerbils. Neurochem. Res. 15:487–493.
Komatsu, M., Hiramatsu, M., Yokoyama, H., and Willmore, L. J. 1996. Effect of TJ-960 (a Japanese herbal medicine) on free radical changes within an iron-induced focal epileptogenic region in rat brain measured by in vivo L-band electron spin resonance. Neurosci. Lett. 205:189–192.
Hamada, H., Hiramatsu, M., Edamatsu, R., and Mori, A. 1993. Free radical scavenging action of baicalein. Arch. Biochem. Biophys. 306:261–266.
Hiramatsu, M., Haba, K., Edamatsu, R., Hamada, H., and Mori, A. 1989. Increased choline acetyltransferase activity by Chinese herbal medicine Sho-saiko-to-go-keishi-ka-shakuyaku-to in aged rat brain. Neurochem. Res. 14:249–251.
Inada, K., Yokoi, I., Kabuto, H., Habu, H., Mori, A., and Ogawa, N. 1996. Age-related increase in nitric oxide synthase activity in senescence accelerated mouse brain and the effect of long-term administration of superoxide radical scavenger. Mechan. Age. Dev. 89:95–102.
Ueda, Y., Komatsu, M., and Hiramatsu, M. 1996. Free radical scavenging activity of the Japanese herbal medicine tokishakuyaku-san (TJ-23) and its effect on superoxide dismutase activity, lipid peroxides, glutamate, and monoamine metabolites in aged rat brain. Neurochem. Res. 21:909–914.
Ondrias, K., Stasko, A., Gergel, D., Hromadova, M., and Benes, L. 1992. Formation of stable free radicals from kampo medicines TJ-9, TJ-15, TJ-23, TJ-96, TJ-114 and their antioxidant effect on low density lipoproteins. Free Rad. Res. Commun. 16:227–237.
Hasegawa, T. 1984. Clinical effect of Oren-gedoku-to on cerebrovascular disorders. In: Oda T. et al, eds. Recent advances in traditional medicine in East Asia, ICS693. Tokyo: Excepta Medica. 209–218.
Ginsberg, M. D. and Busto, R. 1989. Rodent models of cerebral ischemia. Stroke 20:1627–1642.
Sweeney, M. I., Yager, J. Y., Walz, W., and Juurlink, B. H. 1995. Cellular mechanisms involved in brain ischemia. Can. J. Physiol. Pharmacol. 73:1525–1535.
Abe, K., Aoki, M., Kawagoe, J., Yoshida, T., Hattori, A., Kogure, K., and Itoyama, Y. 1995. Ischemic delayed neuronal death. A mitochondrial hypothesis. Stroke 26:1478–1489.
Chan, P. H. 1994. Oxygen radicals in focal cerebral ischemia. Brain Pathol. 4:59–65.
Yang, G., Chan, P. H., Chen, J., Carlson, E., Chen, S. F., Weinstein, P., Epstein, C. J., and Kamii, H. 1994. Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke 25:165–170.
Kondo, T., Reaume, A. G., Huang, T. T., Carlson, E., Murakami, K., Chen, S. F., Hoffman, E. K., Scott, R. W., Epstein, C. J., and Chan, P. H. 1997. Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J. Neurosci. 17:4180–4189.
Kitagawa, K., Matsumoto, M., Yang, G., Mabuchi, T., Yagita, Y., Hori, M., and Yanagihara, T. 1998. Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery. J. Cereb. Blood Flow Metab. 18:570–579.
Yang, G., Kitagawa, K., Matsushita, K., Mabuchi, T., Yagita, Y., Yanagihara, T., and Matsumoto, M. 1997. C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia. Brain Res. 752:209–218.
Kondo, Y., Asanuma, M., Nishibayashi, S., Iwata, E., and Ogawa, N. 1997. Late-onset lipid peroxidation and neuronal cell death following transient forebrain ischemia in rat brain. Brain Res. 772:37–44.
Petito, C. K. and Pulsinelli, W. A. 1984. Delayed neuronal recovery and neuronal death in rat hippocampus following severe cerebral ischemia: possible relationship to abnormalities in neuronal processes. J. Cereb. Blood Flow Metab. 4:194–205.
Ito, U., Spatz, M., J. T., W., and Klatzo, I. 1975. Experimental cerebral ischemia in Mongolian gerbils. I. Light microscopic observations. Acta Neuropathol. (Berl) 32:209–223.
Kirino, T. 1982. Delayed neuronal death in the gerbil hippocampus following transient ischemia. Brain Res. 239:57–69.
Wu, W., Kuang, P., and Zhu, K. 1992. The effect of radix Salviae miltiorrhizae on the changes of ultrastructure in rat brain after cerebral ischemia. J. Trad. Chin. Med. 12:183–186.
Du, G. and Zhang, J. 1997. Protective effects of salvianolic acid A against impairment of memory induced by cerebral ischemiareperfusion in mice. Chin. Med. J. 110:65–68.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kondo, Y., Kondo, F., Asanuma, M. et al. Protective Effect of Oren-gedoku-to Against Induction of Neuronal Death by Transient Cerebral Ischemia in the C57BL/6 Mouse. Neurochem Res 25, 205–209 (2000). https://doi.org/10.1023/A:1007515318434
Issue Date:
DOI: https://doi.org/10.1023/A:1007515318434