Neurochemical Research

, Volume 20, Issue 2, pp 115–119 | Cite as

Baclofen is cytoprotective to cerebral ischemia in gerbils

  • Sumeer Lal
  • Ashfaq Shuaib
  • Sadiq Ijaz
Original Articles

Abstract

The release of the neurotransmitter, glutamate, and the activation of receptor operated calcium channels, may increase the degree of damage in ischemic brain tissue. Inhibition of excitatory neurotransmitters should therefore result in cytoprotection of ischemic brain tissue. In this study we evaluated the effect of baclofen, an inhibitor of presynaptic glutamate release, on ischemic gerbil cortex, hippocampus (CA 1 and CA4), striatum and thalamus. Histological evaluation was done in a blind manner in 4 groups (total 36 animals): a control group (9 animals) and three groups (27 animals) with varying doses of baclofen. For cerebral ischemia, we used single episode of five minutes of arterial occlusion of the carotid arteries. Baclofen in doses of 0, 25, 50, and 100 mg/kg were given to different groups five minutes prior to ischemic insult. This was followed by intraperitoneal injections given 24 and 48 hours after the initial insult. Statistically significant histological cytoprotection was demonstrated. Doses of 25 mg/kg appeared to demonstrate significant protection of the cortex (p=0.0002), the CA1 and CA4 regions of the hippocampus (p=0.0004 and 0.0001) respectively. At a dose of 50 mg/kg, significant cytoprotection was demonstrated at the hippocampus (CA1 and CA4 regions), in particular at the CA4 region (p=0.0029). The 100 mg/kg dose appeared to have most significant protection at the CA1 and CA4 regions of the hippocampus (both p=0.0001), striatum (p=0.0011), and the thalamus (p=0.0008). All statistical comparisons were done using non-parametric tests (Mann-Whitney U test). Our study demonstrates that baclofen is cytoprotective to ischemic neuronal cells, especially in the hippocampus. Clinically this may be beneficial to those patients with strokes or head injuries.

Key Words

Baclofen ischemia gerbils cerebral 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pullsinelli, W. A., Brierly J. B., and Plein F. 1982. Temporal profile of neuronal damage in a model of transient ischemia. Ann. Neurol. 11:491–498.Google Scholar
  2. 2.
    Kitagawa K., Matsumoto M., Oda T., Miinobe M., Hata, R., Handa N., Fukunaga R., Isaka Y., Kimura K., Maeda H., Mikoshiba K., and Kanada T. 1990. Free radical gerneration during brief period of cerebral ischemia may trigger the delayed neuronal death. Neuroscience, 35:551–558.Google Scholar
  3. 3.
    Rosenbaum D., Grotta J. C., Pettigrew C., Ostrow P., Strong R., Rhoades H., Picone C., and Grotta A. 1989. Baclofen does not protect against cerebral ischemia in rats. Stroke, 21:138–140.Google Scholar
  4. 4.
    Shuaib A., Mazagri R., and Ijaz S. 1993. GABA agonist “Muscimol” Is Neuroprotective in Repetitive Transient Forebrain Ischemia in Gerbils. Exp. Neur. 123:284–288.Google Scholar
  5. 5.
    Simpson R. E., O'Regan M. H., Perkins L. M., and Phillis J. W. 1992. Excitatory Transmitter Amino Acid Release from the Ischemic Rat Cerebral Cortex: Effects of Adenosine Receptor Agonists and Antagonists. J. Neurochem 58:1683–1690.Google Scholar
  6. 6.
    Rothman, S., and Olney J. W. 1986. Glutamate and the pathophysiology of hypoxicischemic brain damage. Ann Neurol, 19: 105–111.Google Scholar
  7. 7.
    Hara H., Sukamoto T., and Kogure K. 1993. Mechanism and Pathogenesis of Ischemia-Induced Neuronal Damage. Prog. in Neurobiol. 40:645–670.Google Scholar
  8. 8.
    Sternau L. L., Lust W. D., Ricci A. J., and Ratcheson R. 1989. Role for gamma-aminobutyric acid in selective vulnerability in gerbils. Stroke 20:281–287.Google Scholar
  9. 9.
    Gallyas F., Wolff J. R., Bottcher H., and Zaborskzky L. 1980. A reliable and sensitive method to localize terminal degeneration and lysosomes in central nervous system. Stain Tech. 55:299–306.Google Scholar
  10. 10.
    Gallyas F., Wolff J. R., Bottcher H., and Zaborskzky L. 1980. A reliable method to localize axonal damage after axotomy. Stain Tech. 55:291–297.Google Scholar
  11. 11.
    Loskota W. J., Lomax P., and Vertiy M. 1974. A Stereotactic atlas of Mongolian gerbil brain. Ann Arbor Publishers Inc., Ann Arbor.Google Scholar
  12. 12.
    Shuaib A., Ijaz S., Kalra J., and Code W. 1992. Repetitive transient forebrain ischemia in gerbils: delayed neuronal damage in the substania nigra reticulata. Brain Res. 574:120–124.Google Scholar
  13. 13.
    Gonzales C., Lin R. C.-S., and Chesselet M.-F. 1991. Relative sparing of GABAergic interneurons in the striatum of gerbils with ischemia-induced lesions. Neurosci Lett. 135:53–58.Google Scholar
  14. 14.
    Ginsberg M., and Busto R. 1989. Rodent Models of Cerebral Ischemia. Stroke 20:1627–1642.Google Scholar
  15. 15.
    Mies G., Kloiber O., Drewes L., and Hossmann K.-A. 1984. Cerebral blood flow and regional potassium distribution during focal ischemia of gerbil brain. Ann Neurol. 16:232–237.Google Scholar
  16. 16.
    Oostveen J., Timby K., and Williams L. 1992. Prediction of Cerebral Ischemia by o opthalmoscopy after carotid after carotid occlusion in gerbils. Stroke 23:1588–1594.Google Scholar
  17. 17.
    Nagasawa H., Izumiyama K., and Kogure K. 1991. Effect of mergocriptine on postischemic brain damages. Drug Res. 41:1119–1122.Google Scholar
  18. 18.
    Tagaya, M., Matsumoto M., Kitagawa K., Niinobe M., Ohtsuki T., Hat R., Ogawa S., Handa N., Mikoshiba K., and Kamada T. 1992. Recombinant Human Dimutase can attenuate ischemic neuronal damage in gerbils. Life Sci. 51:253–259.Google Scholar
  19. 19.
    Zager E., and Ames A. 1988. Reduction of cellular energy requirements. J Neurosurgery 69:568–579.Google Scholar
  20. 20.
    Xie Y., Mies G., and Hossmann K. 1989. Ischemic threshold of brain protein synthesis after unilateral carotid artery occlusion in gerbils. Stroke 20:620–626.Google Scholar
  21. 21.
    Kitagawa K., Matsumoto M., Tagaya M., Hata R., Ueda H., Niinobe M., Handa N., Fukunaga R., Kimura K., Mikoshiba K., and Kamada T. 1990. ‘Ischemic tolerance’ phenomenon found in the brain. Brain Res. 528:21–24.Google Scholar
  22. 22.
    Garcia J. H., and Anderson M. L. 1989. Pathophysiology of cerebral ischemia. CRC. Crit. Rev. Neurobiol. 4:303–324.Google Scholar
  23. 23.
    Choi, D. W. 1990. Methods of antagonizing glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu. Rev. 13: 171–182.Google Scholar
  24. 24.
    Choi, D. W. 1988. Calcium mediated neurotoxicity: Relationship to specific channel types and role in ischemic damage. Trends Neurosci. 11:465–469.Google Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Sumeer Lal
    • 3
  • Ashfaq Shuaib
    • 1
  • Sadiq Ijaz
    • 2
  1. 1.The Department of Medicine, The Saskatchewan Stroke Research CentreUniversity of SaskatchewanSaskatoonCanada
  2. 2.Cerebrovascular Research Labratory, The Saskatchewan Stroke Research CentreUniversity of SaskatchewanSaskatoonCanada
  3. 3.Division of Neurosurgery, Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonCanada

Personalised recommendations