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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Endocannabinoids potently protect the newborn brain against AMPA-kainate receptor-mediated excitotoxic damage
British Journal of Pharmacology, Volume 148, No. 4, Year 2006
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Description
1 Brain lesions induced in newborn mice or rats by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) or S-bromowillardiine (acting on AMPA-kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage associated with cerebral palsy. Exogenous and endogenous cannabinoids have received increasing attention as potential neuroprotective agents in a number of neurodegenerative disorders of the adult. One recent study showed neuroprotection by the cannabinoid agonist WIN-55212 in a newborn rat model of acute severe asphyxia. 2 The present study was designed to assess the neuroprotective effects of the endogenous cannabinoid anandamide using a well-defined rodent model of neonatal excitotoxic brain lesions. 3 In this model, anandamide provided dose-dependent and long-lasting protection of developing white matter and cortical plate reducing the size of lesions induced by S-bromowillardiine. Anandamide had only marginal neuroprotective effect against ibotenate-induced cortical grey matter lesions. Anandamide-induced neuroprotection against AMPA-kainate receptor-mediated brain lesions were blocked by a CB1 antagonist but not by a CB2 antagonist. Furthermore, anandamide effects were mimicked by a CB1 agonist but not by a CB2 agonist. Real-time PCR confirmed the expression of CB1 receptors, but not CB2 receptors, in the untreated newborn neocortex. Finally, neuroprotective effects of anandamide in white matter involved increased survival of preoligodendrocytes and better preservation of myelination. 4 The present study provides experimental support for the role of endocannabinoids as a candidate therapy for excitotoxic perinatal brain lesions. © 2006 Nature Publishing Group All rights reserved.
Authors & Co-Authors
Shouman, B.
France, Paris
Hôpital Robert-debré Ap-hp
France, Paris
Université Paris Cité
Egypt, Mansoura
Mansoura University Children's Hospital
Fontaine, Romain H.
France, Paris
Hôpital Robert-debré Ap-hp
France, Paris
Université Paris Cité
Baud, Olivier
France, Paris
Hôpital Robert-debré Ap-hp
France, Paris
Université Paris Cité
Schwendimann, L.
France, Paris
Hôpital Robert-debré Ap-hp
France, Paris
Université Paris Cité
Keller, Matthias
Austria, Innsbruck
Medizinische Universitat Innsbruck
Spedding, Michael
France, Neuilly-sur-seine
Servier
Lelièvre, Vincent
France, Paris
Hôpital Robert-debré Ap-hp
France, Paris
Université Paris Cité
Gressens, Pierre
France, Paris
Hôpital Robert-debré Ap-hp
France, Paris
Université Paris Cité
Statistics
Citations: 64
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1038/sj.bjp.0706755
ISSN:
00071188
e-ISSN:
14765381
Research Areas
Disability
Maternal And Child Health