Skip to main content
Log in

Substrain Differences, Gender, and Age of Spontaneously Hypertensive Rats Critically Determine Infarct Size Produced by Distal Middle Cerebral Artery Occlusion

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

1. The present work discussed the effects of substrain or genetic differences, gender, and age of the rat on infarct size produced by distal middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR).

2. In SHR/Kyushu, infarct volume was significantly larger than that of SHR/Izm, while blood pressure levels were essentially the same between the two substrains. Although SHR-SP/Izm had a higher blood pressure than SHR/Kyushu, infarct volumes were the same between SHR/Kyushu and SHR-SP/Izm. These results suggest the presence of blood pressure- independent factors which affect the infarct size after MCAO.

3. Estrogen accounted the large part of greater tolerability against focal brain ischemic injury in female compared with male SHR.

4. We found age-related vulnerability to focal cerebral ischemia in female SHR. This age-related vulnerability in aged female SHR was unrelated to the blood levels of sex hormones such as estrogens and progesterone.

5. Finally, we emphasized the importance of reproducible and least invasive focal ischemia models in stroke research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  • Alkayed, N. J., Goto, S., Sugo,N., Joh, H.-D., Klaus, J., Crain, B. J., Bernard, O., Traystman, R. J., and Hurn, P. D. (2001). Estrogen and Bcl-2: Gene induction and effect of transgene in experimental stroke. J. Neurosci. 21:7543–7550.

    PubMed  Google Scholar 

  • Alkayed, N. J., Harukuni, I., Kimes, A. S., London, E. D., Traystman, R. J., and Hurn, P. D. (1998). Gender-linked brain injury in experimental stroke. Stroke 29:159–166.

    PubMed  Google Scholar 

  • Alkayed, N. J., Murphy, J., Traystman, R. J., and Hurn, P. D. (2000). Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 31:161–168.

    PubMed  Google Scholar 

  • Cai, H., Yao, H., Ibayashi, S., Uchimura, H., and Fujishima, M. (1998). Photothrombotic middle cerebral artery occlusion in spontaneously hypertensive rats: Influence of substrain, gender and distal middle cerebral artery patterns on infarct size. Stroke 29:1982–1987.

    PubMed  Google Scholar 

  • Carr, F. J., McBride, M. W., Carswell, H. V. O., Graham, D., Strahorn, P., Clark, J. S., Charchar, F. J., and Dominiczak, A. F. (2002). Genetic aspects of stroke: Human and experimental studies. J. Cereb. Blood Flow Metab 22:767–773.

    PubMed  Google Scholar 

  • Carswell, H. V. O., Dominiczak, A. F., and Macrae, I.M. (2002). Estrogen status affects sensitivity to focal cerebral ischemia in stroke-prone spontaneously hypertensive rats. Am. J. Physiol. 278:H290–H294.

    Google Scholar 

  • Chen, D., Cao, G., Hastings, T., Feng, Y., Pei, W., O'Horo, C., and Chen, J. (2002). Age-related decline of DNA repair activity for oxidative lesions in rat brain mitochondria. J. Neurochem 81:1273–1284.

    PubMed  Google Scholar 

  • Coyle, P., and Jokelainen, P. T. (1983). Differential outcome to middle cerebral artery occlusion in spontaneously hypertensive stroke-prone rats (SHRSP) andWistar Kyoto (WKY) rats. Stroke 14:605–611.

    PubMed  Google Scholar 

  • Coyle, P., Odenheimer, D. J., and Sing, C. F. (1984). Cerebral infarction after middle cerebral artery occlusion in progenies of spontaneously stroke-prone and normal rats. Stroke 15:711–716.

    PubMed  Google Scholar 

  • Davis, M., Mendelow, A.D., Perry, R. H., Chambers, I. R., and James, O. F.W. (1995). Experimental stroke and neuroprotection in the aging rat brain. Stroke 26:1072–1078.

    PubMed  Google Scholar 

  • Dominiczak, A. F., Clark, J. S., Jeffs, B., Anderson, N. H., Negrin, C. D., Lee, W. K., and Brosnan, M. J. (1998). Genetics of experimental hypertension. J. Hypertens. 16:1859–1869.

    PubMed  Google Scholar 

  • Dubal, D. B., Kashon, M. L., Pettigrew, L. C., Ren, J. M., Finklestein, S. P., Rau, S. W., and Wise, P. M. (1998). Estradiol protects against ischemic injury. J. Cereb. Blood Flow Metab. 18:1253–1258.

    PubMed  Google Scholar 

  • Dubal, D. B., Shughrue, P. J., Wilson, M. E., Merchenthaler, I., and Wise, P.M. (1999). Estradiol modulates bcl-2 in cerebral ischemia: A potential role for estrogen receptors. J. Neurosci. 19:6385–6393.

    PubMed  Google Scholar 

  • Dubal, D. B., and Wise, P. M. (2001). Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology 142:43–48.

    PubMed  Google Scholar 

  • Fujii, K., Weno, B. L., Baumbach, G. L., and Heistad, D. D. (1992). Effect of antihypertensive treatment on focal cerebral infarction. Hypertension 19:713–716.

    PubMed  Google Scholar 

  • Fujishima, M., Sadoshima, S., Ogata, J., Yoshida, F., Shiokawa, O., Ibayashi, S., and Omae, T. (1984). Autoregulation of cerebral blood flow in young and aged spontaneously hypertensive rats (SHR). Gerontology 30:30–36.

    PubMed  Google Scholar 

  • Fukuda, K., Yao, H., Ibayashi, S., Nakahara, T., Uchimura, H., and Fujishima, M. (2000). Ovariectomy exacerbates and estrogen replacement attenuates photothrombotic focal ischemic injury in rats. Stroke 31:155–160.

    PubMed  Google Scholar 

  • Ginsberg, M. D., and Busto, R. (1989). Rodent models of cerebral ischmeia. Stroke 20:1627–1642.

    PubMed  Google Scholar 

  • Gratton, J. A., Sauter, A., Rudin, M., Lees, K. R., McColl, J., Reid, J. L., Dominiczak, A. F., and Macrae, I. M. (1998). Susceptibility to cerebral infarction in the stroke-prone spontaneously hypertensive rat is inherited as a dominant trait. Storke 29:690–694.

    Google Scholar 

  • Hurn, P.D., and Macrae, I.M. (2000). Estrogen as a neuroprotectant in stroke. J. Cereb. Blood FlowMetab. 20:631–652.

    Google Scholar 

  • Ikeda, K., Nara, Y., Matumoto, C., Mashimo, T., Tamada, T., Sawamura, M., Nabika, T., and Yamori, Y. (1996). The region responsible for stroke on chromosome 4 in the stroke-prone spontaneously hyertensive rat. Biochem. Biophys. Res. Commun. 229:658–662.

    PubMed  Google Scholar 

  • Jeffs, B., Clark, J. S., Anderson, N. H., Gratton, J., Brosnan, M. J., Gauguier, D., Reid, J. L., Macrae, I. M., and Dominiczak, A. F. (1997). Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus. Nature Genet. 16:364–367.

    PubMed  Google Scholar 

  • Nabika, T., Kobayashi, Y., and Yamori, Y. (2000). Congenic rats for hypertension: How useful are they for the hunting of hypertension genes? Clin. Exp. Pharmacol. Physiol. 27:251–256.

    PubMed  Google Scholar 

  • Navarro, A., Sanchez-del-Pino, M. J., Gomez, C., Peralta, J. L., and Boveris, A. (2002). Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice. Am. J. Physiol. 282:R985-R992.

    Google Scholar 

  • Ogata, J., Fujishima, M., Morotomi,Y., and Omae, T. (1976). Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: A pathological study. Stroke 7:54–60.

    PubMed  Google Scholar 

  • Okamoto, K., and Aoki, K. (1963). Development of a strain of spontaneously hypertensive rats. Jpn. Circ. J. 27:282–293.

    PubMed  Google Scholar 

  • Ooboshi, H., Sadoshima, S., Yao, H., Ibayashi, S., Matsumoto, T., Uchimura, H., and Fujishima, M. (1995). Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats. J. Cereb. BloodFlow Metab. 15:227–234.

    Google Scholar 

  • Popa-Wagner, A., Schroder, E., Schomoll, H., Walker, L. C., and Kessler, C. (1999). Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery occlusion: Effect of age. J. Cereb.Blood Flow Metab. 19:425–434.

    PubMed  Google Scholar 

  • Popa-Wagner, A., Schroder, E., Walker, L. C., and Kessler, C. (1998). ß-amyloid precursor protein and ß-amyloid peptide immunoreactivity in the rat brain after middle cerebral artery occlusion. Effect of age. Stroke 29:2196–2202.

    PubMed  Google Scholar 

  • Rubattu, S., Giliberti, R., and Volpe, M. (2000). Etiology and pathophysiology of stroke as a complex trait. Am. J. Hypertens. 13:1139–1148.

    PubMed  Google Scholar 

  • Rubattu, S., Volpe, M., Kreutz, R., Ganten, U., Ganten, D., and Lindpaintner, K. (1996). Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease. Nature Genet. 13:429–434.

    PubMed  Google Scholar 

  • Rusa, R., Alkayed, N. J., Crain, B. J., Traystman, R. J., Kimes, A. S., London, E. D., Klaus, J. A., and Hurn, P. D. (1999). 17ß-estradiol reduces stroke injury in estrogen-deficient female animals. Stroke 30:1665–1670.

    PubMed  Google Scholar 

  • Sutherland, G. R., Dix, G. A., and Auer, R.N. (1996). Effect of age in rodent models of focal and forebrain ischemia. Stroke 27:1663–1668.

    PubMed  Google Scholar 

  • Tamaki, K., Fujishima, M., Ogata, J., Nakatomi, Y., Ishitsuka, T., Sadoshima, S., and Omae, T. (1979). Effects of aging on cerebal metabolism following bilaterlal carotid ligation in male spontaneously hypertensive rats (SHR). Brain Res. 170:368–371.

    PubMed  Google Scholar 

  • Tamaki, K., Nakai, M., Yokota, T., and Ogata, J. (1995). Effects of aging and chronic hypertension on cerebral blood flow and cerebrovascualr CO2 reactivity in the rat. Gerontology 41:11–17.

    PubMed  Google Scholar 

  • Tanizaki, Y., Kiyohara, Y., Kato, I., Iwamoto, H., Nakayama, K., Shinohara, N., Arima, H., Tanaka, K., Ibayashi, S., and Fujishima, M. (2000). Incidence and risk factors for subtypes of cerebral infarction in a general population. Stroke 31:2616–2622.

    PubMed  Google Scholar 

  • Yamori, Y. (1991) Overview: Studies on spontaneously hypertension-development from animal toward man. Clin. Exp. Hypertens. A13:631–644.

    Google Scholar 

  • Yao, H., Ibayashi, S., Sugimori, H., Fujii, K., and Fujishima, M. (1996). Simplified model of krypton laserinduced thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats. Stroke 27:333–336.

    PubMed  Google Scholar 

  • Yao, H., Sadoshima, S., Ooboshi, H., Sato, Y., Uchimura, H., and Fujishima, M. (1991). Age-related vulnerability to cerebral ischemia in spontaneously hypertensive rats. Stroke 22:1414–1418.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takaba, H., Fukuda, K. & Yao, H. Substrain Differences, Gender, and Age of Spontaneously Hypertensive Rats Critically Determine Infarct Size Produced by Distal Middle Cerebral Artery Occlusion. Cell Mol Neurobiol 24, 589–598 (2004). https://doi.org/10.1023/B:CEMN.0000036400.55503.5e

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:CEMN.0000036400.55503.5e

Navigation