| Abstract | Stroke is a major cause of morbidity and mortality and follows heart disease and cancer as the third leading cause of death in Western societies [1]. Despite many advances in stroke research and pharmacotherapy, clinical treatment of this debilitating disorder is still inadequate. Recent findings from several laboratories have identified the endocannabinoid signaling pathway, comprised of the endocannabinoid agonist anandamide and its pharmacological targets, CB1 and CB2 cannabinoid receptors and associated anandamide receptors, as a physiological system with capacity to mitigate cardiovascular and cerebrovascular disorders through neuronal and endothelial actions. Variability in experimental stroke models and modes of outcome evaluation, however, have provoked controversy regarding the precise roles of endocannabinoid signals in mediating neural and/or vascular protection versus neurovascular damage. Clinical trials of the CB1 antagonist rimonabant demonstrate that modulation of endocannabinoid signaling during metabolic regulation of vascular disorders can significantly impact clinical outcomes, thus providing strong argument for therapeutic utility of endocannabinoids and/or cannabinoid receptors as targets for therapeutic intervention in cases of stroke and associated vascular disorders. The purpose of this review is to provide updated information from basic science and clinical perspectives on endocannabinoid ligands and their effects in the pathophysiologic genesis of stroke. Particular emphasis will be placed on the endocannabinoids anandamide and 2-arachidonylglycerol and CB1 receptor-mediated mechanisms in the neurovascular unit during stroke pathogenesis. Deficiencies in our knowledge of endocannabinoids in the etiology and pathogenesis of stroke, caveats and limitations of existing studies, and future directions for investigation will be addressed. |
| Authors | Somnath Mukhopadhyay, David A Tulis
(Affiliation: J.L. Chambers Biomedical/Biotechnology Research Institute, Department of Biology, North Carolina Central University, 700 George Street, Durham, NC 27707, USA.)
|
| Journal | Cardiovascular & hematological agents in medicinal chemistry
(Cardiovasc Hematol Agents Med Chem)
Vol. 5
Issue 4
Pg. 311-8
(Oct 2007)
ISSN: 1871-5257 Netherlands |
| PMID | 17979695
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
|
| Chemical References |
- Arachidonic Acids
- Endocannabinoids
- Glycerides
- Polyunsaturated Alkamides
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- 2-arachidonylglycerol
- anandamide
- Matrix Metalloproteinases
|
| Topics |
- Arachidonic Acids
(physiology)
- Brain Ischemia
(physiopathology)
- Endocannabinoids
(physiology)
- Glycerides
(physiology)
- Humans
- Matrix Metalloproteinases
(physiology)
- Polyunsaturated Alkamides
- Receptor, Cannabinoid, CB1
(physiology)
- Receptor, Cannabinoid, CB2
(physiology)
- Signal Transduction
- Stroke
(physiopathology)
|
