Modulation of Cannabinoid Receptor Activation as a Neuroprotective Strategy for EAE and Stroke

Modulation of Cannabinoid Receptor Activation as a Neuroprotective Strategy for EAE and Stroke Recognition of the importance of the endocannabinoid system in both homeostasis and pathologic responses raised interest recently in the development of therapeutic agents based on this system. The CB2 receptor, a component of the endocannabinoid system, has significant influence on immune function and inflammatory responses. Inflammatory responses are major contributors to central nervous system (CNS) injury in a variety of diseases. In this report, we present evidence that activation of CB2 receptors, by selective CB2 agonists, reduces inflammatory responses that contribute to CNS injury. The studies demonstrate neuroprotective effects in experimental autoimmune encephalomyelitis, a model of multiple sclerosis, and in a murine model of cerebral ischemia/reperfusion injury. In both cases, CB2 receptor activation results in reduced white cell rolling and adhesion to cerebral microvessels, a reduction in immune cell invasion, and improved neurologic function after insult. In addition, administration of the CB1 antagonist SR141716A reduces infarct size following ischemia/reperfusion injury. Administration of both a selective CB2 agonist and a CB1 antagonist has the unique property of increasing blood flow to the brain during the occlusion period, suggesting an effect on collateral blood flow. In summary, selective CB2 receptor agonists and CB1 receptor antagonists have significant potential for neuroprotection in animal models of two devastating diseases that currently lack effective treatment options. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroimmune Pharmacology Springer Journals

Modulation of Cannabinoid Receptor Activation as a Neuroprotective Strategy for EAE and Stroke

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Publisher
Springer Journals
Copyright
Copyright © 2009 by Springer Science+Business Media, LLC
Subject
Biomedicine; Cell Biology; Virology ; Pharmacology/Toxicology ; Immunology; Neurosciences
ISSN
1557-1890
eISSN
1557-1904
D.O.I.
10.1007/s11481-009-9148-4
Publisher site
See Article on Publisher Site

Abstract

Recognition of the importance of the endocannabinoid system in both homeostasis and pathologic responses raised interest recently in the development of therapeutic agents based on this system. The CB2 receptor, a component of the endocannabinoid system, has significant influence on immune function and inflammatory responses. Inflammatory responses are major contributors to central nervous system (CNS) injury in a variety of diseases. In this report, we present evidence that activation of CB2 receptors, by selective CB2 agonists, reduces inflammatory responses that contribute to CNS injury. The studies demonstrate neuroprotective effects in experimental autoimmune encephalomyelitis, a model of multiple sclerosis, and in a murine model of cerebral ischemia/reperfusion injury. In both cases, CB2 receptor activation results in reduced white cell rolling and adhesion to cerebral microvessels, a reduction in immune cell invasion, and improved neurologic function after insult. In addition, administration of the CB1 antagonist SR141716A reduces infarct size following ischemia/reperfusion injury. Administration of both a selective CB2 agonist and a CB1 antagonist has the unique property of increasing blood flow to the brain during the occlusion period, suggesting an effect on collateral blood flow. In summary, selective CB2 receptor agonists and CB1 receptor antagonists have significant potential for neuroprotection in animal models of two devastating diseases that currently lack effective treatment options.

Journal

Journal of Neuroimmune PharmacologySpringer Journals

Published: Mar 3, 2009

References

  • Cerebral hypoxia–ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain
    Ashton, JC; Rahman, RM
  • CB1 cannabinoid receptor induction in experimental stroke
    Jin, KL; Mao, XO
  • Cannabinoid-induced immune suppression and modulation of antigen-presenting cells
    Klein, TW; Cabral, GA
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    Klein, TW; Newton, C
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    Mackie, K
  • CNS dendritic cells: critical participants in CNS inflammation
    McMahon, EJ; Bailey, SL
  • Characterisation of the vasorelaxant properties of the novel endocannabinoid N-arachidonoyl-dopamine (NADA)
    O'Sullivan, SE; Kendall, DA
  • Heterogeneity in the mechanisms of vasorelaxation to anandamide in resistance and conduit rat mesenteric arteries
    O'Sullivan, SE; Kendall, DA
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    Pacher, P; Hasko, G
  • Endocannabinoids potently protect the newborn brain against AMPA-kainate receptor-mediated excitotoxic damage
    Shouman, B; Fontaine, RH
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    Stella, N
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    Weaver, M; Leshley, K

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