Display options
Cite
Harry GJ, Sills R, Schlosser MJ, et al. Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME). Neurotox Res. 2001;3(3):307-19doi: 10.1007/BF03033270.
Harry, G. J., Sills, R., Schlosser, M. J., & Maier, W. E. (2001). Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME). Neurotoxicity research, 3(3), 307-19. https://doi.org/10.1007/BF03033270
Harry, G J, et al. "Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME)." Neurotoxicity research vol. 3,3 (2001): 307-19. doi: https://doi.org/10.1007/BF03033270
Harry GJ, Sills R, Schlosser MJ, Maier WE. Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME). Neurotox Res. 2001 Jul;3(3):307-19. doi: 10.1007/BF03033270. PMID: 15111256.
Copy Download .nbib Format: NLM
Share it on

Neurotox Res. 2001 Jul;3(3):307-19. doi: 10.1007/BF03033270.

Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME).

Neurotoxicity research

G J Harry, R Sills, M J Schlosser, W E Maier

Affiliations

  1. National Institute for Environmental Health Sciences, Research Triangle Park, NC, USA. [email protected]

PMID: 15111256 DOI: 10.1007/BF03033270

Abstract

Hippocampal neurodegeneration and glia response was examined following administration of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME). Male Long-Evans rats received L-NAME (50 mg/kg, ip) either once or twice a day for 4 days. Both dosing schedules decreased NOS-activity by approximately 90%. At 10 and 30 days following cessation of L-NAME (2x/day), moderate neuronal death was evident in CA1-2 pyramidal cells and dentate granule cells. Neurodegeneration was accompanied by increased astrocyte glial fibrillary acidic protein (GFAP) immunoreactivity yet, minimal astrocyte hypertrophy. Microglia response was limited to an increase in ramified microglia at 10 days, returning to normal by 30 days. As early as 4 days post-dosing (2x/day), GFAP mRNA levels were significantly elevated as were mRNA levels for tumor necrosis factor-alpha (TNFalpha), interleukin-1alpha (IL-1alpha), and interleukin 6 (IL-6). No alterations were seen with L-NAME dosing limited to once a day. The co-administration of a hippocampal neurotoxicant, trimethyltin (TMT), with the last dose of L-NAME (2x/day), produced an additive response pattern of neuronal degeneration including both CA1-2 and CA3-4 pyramidal neurons accompanied by TMT-induced astrocyte hypertrophy and prominent microglia reactivity. This was preceded by elevations in mRNA levels for GFAP, TNFalpha, IL-1alpha, and IL-6 similar to those seen with each substance alone. These data suggest that high levels of L-NAME can produce a pro-inflammatory environment in the brain and that neurodegeneration and neuroglia responses in the hippocampus can be induced by an alteration in the balance and regulation of local nitric oxide levels.

References

  1. Brain Res. 1994 Jul 18;651(1-2):92-100 - PubMed
  2. Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1408-16 - PubMed
  3. J Neurosci Res. 1994 Nov 1;39(4):405-11 - PubMed
  4. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10945-9 - PubMed
  5. J Biol Chem. 1993 Jun 15;268(17):12231-4 - PubMed
  6. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682-5 - PubMed
  7. Trends Neurosci. 1993 Aug;16(8):323-8 - PubMed
  8. Clin Exp Pharmacol Physiol. 1995 Apr;22(4):305-8 - PubMed
  9. Adv Neuroimmunol. 1995;5(4):421-30 - PubMed
  10. Biochem Biophys Res Commun. 1991 May 15;176(3):1136-41 - PubMed
  11. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620-4 - PubMed
  12. Neurochem Res. 1994 Apr;19(4):501-5 - PubMed
  13. Biochem Biophys Res Commun. 1992 Nov 30;189(1):242-9 - PubMed
  14. J Mol Neurosci. 1994-1995;5(4):219-29 - PubMed
  15. Neuroreport. 1992 Jun;3(6):530-2 - PubMed
  16. J Neuroimmunol. 1995 Apr;58(1):81-8 - PubMed
  17. Neuroscience. 1994 Apr;59(4):905-19 - PubMed
  18. Stroke. 1994 Feb;25(2):436-43; discussion 443-4 - PubMed
  19. J Immunol. 1992 Oct 15;149(8):2736-41 - PubMed
  20. J Neurocytol. 1987 Apr;16(2):249-60 - PubMed
  21. J Clin Invest. 1999 Sep;104(5):647-56 - PubMed
  22. J Neurotrauma. 1996 Jan;13(1):11-6 - PubMed
  23. J Neurochem. 1995 Aug;65(2):895-902 - PubMed
  24. J Neuroimmunol. 1995 Jun;59(1-2):65-75 - PubMed
  25. Eur J Pharmacol. 2000 Mar 10;391(1-2):121-6 - PubMed
  26. Cell. 1992 Sep 4;70(5):705-7 - PubMed
  27. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6711-5 - PubMed
  28. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9455-6 - PubMed
  29. Eur J Pharmacol. 1995 Sep 5;283(1-3):47-53 - PubMed
  30. Clin Immunol Immunopathol. 1993 May;67(2):178-83 - PubMed
  31. Nature. 1993 Aug 12;364(6438):626-32 - PubMed
  32. J Neurochem. 1990 Jul;55(1):349-51 - PubMed
  33. Acta Anaesthesiol Sin. 1998 Sep;36(3):127-31 - PubMed
  34. Br J Pharmacol. 1994 Jul;112(3):720-2 - PubMed
  35. Hypertension. 2000 Jan;35(1 Pt 1):86-90 - PubMed
  36. Brain Res. 1992 Aug 7;587(2):250-6 - PubMed
  37. Brain Res Mol Brain Res. 1998 Jan;53(1-2):1-12 - PubMed
  38. J Clin Invest. 1994 Jun;93(6):2684-90 - PubMed
  39. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4214-8 - PubMed
  40. Pharmacol Rev. 1991 Jun;43(2):109-42 - PubMed
  41. FASEB J. 1992 Sep;6(12):3051-64 - PubMed
  42. Cell Mol Neurobiol. 1995 Jun;15(3):341-9 - PubMed
  43. Eur J Pharmacol. 1994 May 2;256(3):241-9 - PubMed
  44. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1330-4 - PubMed
  45. J Neurotrauma. 1999 Mar;16(3):203-12 - PubMed
  46. Eur J Neurosci. 1998 May;10(5):1613-20 - PubMed
  47. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7773-7 - PubMed
  48. Cell Immunol. 1992 Apr 15;141(1):111-20 - PubMed
  49. Ann Neurol. 1992 Sep;32(3):297-311 - PubMed
  50. Neurobiol Dis. 1995 Jun;2(3):145-55 - PubMed
  51. Science. 1992 Jul 24;257(5069):494-6 - PubMed
  52. Neuroscience. 1994 Dec;63(3):679-89 - PubMed
  53. Neurochem Res. 1997 Jan;22(1):81-6 - PubMed
  54. J Neurosci. 1994 Sep;14(9):5147-59 - PubMed
  55. J Neurochem. 1992 Sep;59(3):897-905 - PubMed
  56. Br J Anaesth. 2000 Feb;84(2):183-9 - PubMed
  57. J Clin Invest. 1992 Sep;90(3):879-87 - PubMed
  58. J Biol Chem. 1994 Feb 18;269(7):4705-8 - PubMed
  59. Neuropharmacology. 1998;37(3):323-30 - PubMed
  60. Br J Pharmacol. 1992 Aug;106(4):931-6 - PubMed
  61. Eur J Immunol. 1993 Aug;23(8):2045-8 - PubMed
  62. Neurosci Res. 1993 Nov;18(2):103-7 - PubMed
  63. Circ Res. 1993 Jul;73(1):205-9 - PubMed

Publication Types