title: Cannabinoid receptor activation in the juvenile rat brain results in rapid biomechanical alterations: Neurovascular mechanism as a putative confounding factor.
abstract: We have recently reported cannabinoid-induced rapid changes in the structure of individual neurons. In order to investigate the presence of similar effects at the regional level, measures of brain tissue biomechanics are required. However, cannabinoids are known to alter cerebral blood flow (CBF), putatively resulting in presently unexplored changes in cerebral tissue biomechanics. Here we used magnetic resonance elastography (MRE) and flow-sensitive alternating inversion recovery (FAIR) imaging to measure in vivo alterations of mechanical properties and CBF, respectively, in the rat hippocampus, a brain region with a high density of type-1 cannabinoid receptors (CB1R). Systemic injection of the cannabinoid agonist CP55,940 (0.7 mg/kg) induced a significant stiffness decrease of 10.5 ± 1.2% at 15 minutes. FAIR imaging indicated a comparable decrease (11.3 ± 1.9%) in CBF. Both effects were specific to CB1R activation, as shown by pretreatment with the CB1R-specific antagonist AM251. Strikingly, similar rapid parallel changes of brain elasticity and CBF were also observed after systemic treatment with the hypotensive drug nicardipine. Our results reveal important drug-induced parallel changes in CBF and brain mechanical characteristics, and show that blood flow-dependent tissue softening has to be considered as an important putative confounding factor when cerebral viscoelastic changes are investigated.
authors.affiliation: Laboratory of Imaging Biomarkers, UMR1149 INSERM-University Paris Diderot, Sorbonne Paris Cité, Paris, France These authors contributed equally to this work.
authors.forename: Simon
authors.initials: S
authors.lastname: Chatelin
authors.affiliation: Brain Plasticity Unit, CNRS UMR8249, ESPCI-ParisTech, PSL Research University, Paris, France These authors contributed equally to this work.
authors.forename: Marie
authors.initials: M
authors.lastname: Humbert-Claude
authors.affiliation: Laboratory of Imaging Biomarkers, UMR1149 INSERM-University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Garteiser
authors.affiliation: Brain Plasticity Unit, CNRS UMR8249, ESPCI-ParisTech, PSL Research University, Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Ricobaraza
authors.affiliation: Laboratory of Imaging Biomarkers, UMR1149 INSERM-University Paris Diderot, Sorbonne Paris Cité, Paris, France Department of Radiology, Assistance-Publique Hôpitaux de Paris, Clichy, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilgrain
authors.affiliation: Laboratory of Imaging Biomarkers, UMR1149 INSERM-University Paris Diderot, Sorbonne Paris Cité, Paris, France Department of Radiology, Assistance-Publique Hôpitaux de Paris, Clichy, France.
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Van Beers
authors.affiliation: Laboratory of Imaging Biomarkers, UMR1149 INSERM-University Paris Diderot, Sorbonne Paris Cité, Paris, France These authors contributed equally to this work.
authors.forename: Ralph
authors.initials: R
authors.lastname: Sinkus
authors.affiliation: Brain Plasticity Unit, CNRS UMR8249, ESPCI-ParisTech, PSL Research University, Paris, France These authors contributed equally to this work zsolt.lenkei@espci.fr.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lenkei
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D015986:Confounding Factors, Epidemiologic; D003511:Cyclohexanols / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009474:Neurons / Q000648:ultrastructure*; D051381:Rats; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D055682:Viscoelastic Substances
chemical_list: D063386:Cannabinoid Receptor Agonists; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D055682:Viscoelastic Substances; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
keywords: Cannabinoid receptors; cerebral blood flow; elasticity imaging; elastography; magnetic resonance imaging