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MeSH Review

Brain Ischemia

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Disease relevance of Brain Ischemia

  • Damage to neurons caused by focal cerebral ischemia and epileptic seizures was exacerbated in TNFR-KO mice, indicating that TNF serves a neuroprotective function [1].
  • Thus, COX-2 is transiently induced after SD and focal ischemia by activation of N-methyl-D-aspartic acid-receptors and PLA2, most prominently in cortical neurons that are at a high risk to die after focal brain ischemia [2].
  • This spectrum of pharmacologic activity suggests that TA-3090 would selectively block Ca2+ entry into cerebrovascular smooth muscle through potential-sensitive and receptor-operated Ca2+ channels that would be expected to increase in subarachnoid hemorrhage and cerebral ischemia [3].
  • Diarylguanidines are structurally unrelated to known blockers of NMDA channels and, therefore, represent a new compound series for the development of neuroprotective agents with therapeutic value in patients suffering from stroke, from brain or spinal cord trauma, from hypoglycemia, and possibly from brain ischemia due to heart attack [4].
  • Inducible NOS in glia may, by generating nitric oxide, contribute to the neuronal damage associated with cerebral ischemia and/or demyelinating diseases [5].

Psychiatry related information on Brain Ischemia


High impact information on Brain Ischemia

  • In brain ischemia, gating of postsynaptic glutamate receptors is thought to initiate Ca2+ overload leading to excitotoxic neuronal death [11].
  • The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury [12].
  • Therapeutic use of magnesium sulfate in selected cases of cerebral ischemia and seizure [13].
  • Inactivation of the adenosine A(2A) receptor (A(2A)R) consistently protects against ischemic brain injury and other neural insults, but the relative contribution of A(2A)Rs on peripheral inflammatory cells versus A(2A)Rs expressed on neurons and glia is unknown [14].
  • MMP-9 levels were lower in tPA knockouts compared with wild-type mice after focal cerebral ischemia [15].

Chemical compound and disease context of Brain Ischemia

  • Thus, under conditions that lead to lactate accumulation (cerebral ischemia) this "end product" may be a useful alternative as a substrate for energy metabolism [16].
  • DATA SYNTHESIS: Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition: promotion of cholinergic and serotonergic activity in specific brain regions, maintenance of neural circuitry, favorable lipoprotein alterations, and prevention of cerebral ischemia [17].
  • Estrogen seems more effective as a prophylactic treatment in females at risk for cardiac and ischemic brain injury, whereas progesterone appears to be more helpful in the post-injury treatment of both male and female subjects with acute traumatic brain damage [18].
  • Considered together, these results indicate that polyamine oxidase-derived 3-aminopropanal is a mediator of the brain damaging sequelae of cerebral ischemia, which can be therapeutically modulated [19].
  • Increased Ca2+ influx through activated N-methyl-D-aspartate (NMDA) receptors and voltage-dependent Ca2+ channels (VDCC) is a major determinant of cell injury following brain ischemia [20].

Biological context of Brain Ischemia


Anatomical context of Brain Ischemia


Gene context of Brain Ischemia


Analytical, diagnostic and therapeutic context of Brain Ischemia


  1. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Bruce, A.J., Boling, W., Kindy, M.S., Peschon, J., Kraemer, P.J., Carpenter, M.K., Holtsberg, F.W., Mattson, M.P. Nat. Med. (1996) [Pubmed]
  2. Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2. Miettinen, S., Fusco, F.R., Yrjänheikki, J., Keinänen, R., Hirvonen, T., Roivainen, R., Närhi, M., Hökfelt, T., Koistinaho, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Pharmacology of TA-3090 (8-chloro diltiazem) related to its cerebrovascular protective properties. Bevan, J.A., Kaminow, L., Laher, I., Thompson, L.P. Circulation (1989) [Pubmed]
  4. Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methyl-D-aspartate receptor antagonists with neuroprotective properties. Keana, J.F., McBurney, R.N., Scherz, M.W., Fischer, J.B., Hamilton, P.N., Smith, S.M., Server, A.C., Finkbeiner, S., Stevens, C.F., Jahr, C. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  5. Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Galea, E., Feinstein, D.L., Reis, D.J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  6. Malonate-induced generation of reactive oxygen species in rat striatum depends on dopamine release but not on NMDA receptor activation. Ferger, B., Eberhardt, O., Teismann, P., de Groote, C., Schulz, J.B. J. Neurochem. (1999) [Pubmed]
  7. Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats. Yamamoto, T., Yatsugi, S., Ohno, M., Furuya, Y., Kitajima, I., Ueki, S. Psychopharmacology (Berl.) (1990) [Pubmed]
  8. Radioprotective effect of transferrin targeted citicoline liposomes. Suresh Reddy, J., Venkateswarlu, V., Koning, G.A. Journal of drug targeting. (2006) [Pubmed]
  9. Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance. Ogawa, N., Haba, K., Sora, Y.H., Higashida, A., Sato, H., Ogawa, S. Clinical therapeutics. (1988) [Pubmed]
  10. Steroid-responsive charles bonnet syndrome in temporal arteritis. Razavi, M., Jones, R.D., Manzel, K., Fattal, D., Rizzo, M. The Journal of neuropsychiatry and clinical neurosciences. (2004) [Pubmed]
  11. The enemy at the gates. Ca2+ entry through TRPM7 channels and anoxic neuronal death. Nicotera, P., Bano, D. Cell (2003) [Pubmed]
  12. Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Gervais, F.G., Xu, D., Robertson, G.S., Vaillancourt, J.P., Zhu, Y., Huang, J., LeBlanc, A., Smith, D., Rigby, M., Shearman, M.S., Clarke, E.E., Zheng, H., Van Der Ploeg, L.H., Ruffolo, S.C., Thornberry, N.A., Xanthoudakis, S., Zamboni, R.J., Roy, S., Nicholson, D.W. Cell (1999) [Pubmed]
  13. Therapeutic use of magnesium sulfate in selected cases of cerebral ischemia and seizure. Goldman, R.S., Finkbeiner, S.M. N. Engl. J. Med. (1988) [Pubmed]
  14. Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Yu, L., Huang, Z., Mariani, J., Wang, Y., Moskowitz, M., Chen, J.F. Nat. Med. (2004) [Pubmed]
  15. Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Wang, X., Lee, S.R., Arai, K., Lee, S.R., Tsuji, K., Rebeck, G.W., Lo, E.H. Nat. Med. (2003) [Pubmed]
  16. Lactate-supported synaptic function in the rat hippocampal slice preparation. Schurr, A., West, C.A., Rigor, B.M. Science (1988) [Pubmed]
  17. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. Yaffe, K., Sawaya, G., Lieberburg, I., Grady, D. JAMA (1998) [Pubmed]
  18. Brain damage, sex hormones and recovery: a new role for progesterone and estrogen? Stein, D.G. Trends Neurosci. (2001) [Pubmed]
  19. Cerebral ischemia enhances polyamine oxidation: identification of enzymatically formed 3-aminopropanal as an endogenous mediator of neuronal and glial cell death. Ivanova, S., Botchkina, G.I., Al-Abed, Y., Meistrell, M., Batliwalla, F., Dubinsky, J.M., Iadecola, C., Wang, H., Gregersen, P.K., Eaton, J.W., Tracey, K.J. J. Exp. Med. (1998) [Pubmed]
  20. Neuroprotective effects of gelsolin during murine stroke. Endres, M., Fink, K., Zhu, J., Stagliano, N.E., Bondada, V., Geddes, J.W., Azuma, T., Mattson, M.P., Kwiatkowski, D.J., Moskowitz, M.A. J. Clin. Invest. (1999) [Pubmed]
  21. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. Villa, P., Bigini, P., Mennini, T., Agnello, D., Laragione, T., Cagnotto, A., Viviani, B., Marinovich, M., Cerami, A., Coleman, T.R., Brines, M., Ghezzi, P. J. Exp. Med. (2003) [Pubmed]
  22. Neuroprotection mediated by changes in the endothelial actin cytoskeleton. Laufs, U., Endres, M., Stagliano, N., Amin-Hanjani, S., Chui, D.S., Yang, S.X., Simoncini, T., Yamada, M., Rabkin, E., Allen, P.G., Huang, P.L., Böhm, M., Schoen, F.J., Moskowitz, M.A., Liao, J.K. J. Clin. Invest. (2000) [Pubmed]
  23. BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia. Plesnila, N., Zinkel, S., Le, D.A., Amin-Hanjani, S., Wu, Y., Qiu, J., Chiarugi, A., Thomas, S.S., Kohane, D.S., Korsmeyer, S.J., Moskowitz, M.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  24. Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease? Mengesdorf, T., Jensen, P.H., Mies, G., Aufenberg, C., Paschen, W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  25. Alteration of second messengers during acute cerebral ischemia - adenylate cyclase, cyclic AMP-dependent protein kinase, and cyclic AMP response element binding protein. Tanaka, K. Prog. Neurobiol. (2001) [Pubmed]
  26. Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival. Maeda, Y., Matsumoto, M., Hori, O., Kuwabara, K., Ogawa, S., Yan, S.D., Ohtsuki, T., Kinoshita, T., Kamada, T., Stern, D.M. J. Exp. Med. (1994) [Pubmed]
  27. Neuroprotective activity of a new class of steroidal inhibitors of the N-methyl-D-aspartate receptor. Weaver, C.E., Marek, P., Park-Chung, M., Tam, S.W., Farb, D.H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  28. Beta-amyloid precursor protein transgenic mice that harbor diffuse A beta deposits but do not form plaques show increased ischemic vulnerability: role of inflammation. Koistinaho, M., Kettunen, M.I., Goldsteins, G., Keinänen, R., Salminen, A., Ort, M., Bures, J., Liu, D., Kauppinen, R.A., Higgins, L.S., Koistinaho, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  29. Estrogen is more than just a "sex hormone": novel sites for estrogen action in the hippocampus and cerebral cortex. Shughrue, P.J., Merchenthaler, I. Frontiers in neuroendocrinology. (2000) [Pubmed]
  30. MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Alessandrini, A., Namura, S., Moskowitz, M.A., Bonventre, J.V. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  31. Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Zhang, W.H., Wang, X., Narayanan, M., Zhang, Y., Huo, C., Reed, J.C., Friedlander, R.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  32. Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation. Le, D.A., Wu, Y., Huang, Z., Matsushita, K., Plesnila, N., Augustinack, J.C., Hyman, B.T., Yuan, J., Kuida, K., Flavell, R.A., Moskowitz, M.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  33. Effects of cerebral ischemia in mice deficient in Persephin. Tomac, A.C., Agulnick, A.D., Haughey, N., Chang, C.F., Zhang, Y., Bäckman, C., Morales, M., Mattson, M.P., Wang, Y., Westphal, H., Hoffer, B.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  34. Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophillic] phase II inducers. Satoh, T., Okamoto, S.I., Cui, J., Watanabe, Y., Furuta, K., Suzuki, M., Tohyama, K., Lipton, S.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  35. Protection against ischemic brain injury by protein therapeutics. Asoh, S., Ohsawa, I., Mori, T., Katsura, K., Hiraide, T., Katayama, Y., Kimura, M., Ozaki, D., Yamagata, K., Ohta, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  36. Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage. Wang, X., Yue, T.L., Barone, F.C., White, R.F., Clark, R.K., Willette, R.N., Sulpizio, A.C., Aiyar, N.V., Ruffolo, R.R., Feuerstein, G.Z. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  37. Uptake of radiolabeled ions in normal and ischemia-damaged brain. Dienel, G.A., Pulsinelli, W.A. Ann. Neurol. (1986) [Pubmed]
  38. Enhanced targeting and killing of tumor cells expressing the CXC chemokine receptor 4 by transducible anticancer peptides. Snyder, E.L., Saenz, C.C., Denicourt, C., Meade, B.R., Cui, X.S., Kaplan, I.M., Dowdy, S.F. Cancer Res. (2005) [Pubmed]
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