RT Journal Article
T1 Cannabinoid Type-2 Receptor Drives Neurogenesis and Improves Functional Outcome After Stroke
A1 Bravo Ferrer, Isbel
A1 Cuartero Desviat, María Isabel
A1 Zarruk, Juan G.
A1 Pradillo, Jesús M.
A1 Hurtado Moreno, Olivia
A1 Romera, Victor G.
A1 Díaz Alonso, Javier
A1 García Segura, Juan Manuel
A1 Guzmán, Manuel
A1 Lizasoaín, Ignacio
A1 Galve Roperh, Ismael
A1 Moro, María A.
AB Background and Purpose—Stroke is a leading cause of adult disability characterized by physical, cognitive, and emotional disturbances. Unfortunately, pharmacological options are scarce. The cannabinoid type-2 receptor (CB2R) is neuroprotective in acute experimental stroke by anti-inflammatory mechanisms. However, its role in chronic stroke is still unknown. Methods—Stroke was induced by permanent middle cerebral artery occlusion in mice; CB2R modulation was assessed by administering the CB2R agonist JWH133 ((6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6Hdibenzo[b,d]pyran) or the CB2R antagonist SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo-[2.2.1]-heptan-2-yl]-5-(4- chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide) once daily from day 3 to the end of the experiment or by CB2R genetic deletion. Analysis of immunofluorescence-labeled brain sections, 5-bromo-2´-deoxyuridine (BrdU) staining, fluorescence-activated cell sorter analysis of brain cell suspensions, and behavioral tests were performed. Results—SR144528 decreased neuroblast migration toward the boundary of the infarct area when compared with vehicletreated mice 14 days after middle cerebral artery occlusion. Consistently, mice on this pharmacological treatment, like mice with CB2R genetic deletion, displayed a lower number of new neurons (NeuN+ /BrdU+ cells) in peri-infarct cortex 28 days after stroke when compared with vehicle-treated group, an effect accompanied by a worse sensorimotor performance in behavioral tests. The CB2R agonist did not affect neurogenesis or outcome in vivo, but increased the migration of neural progenitor cells in vitro; the CB2R antagonist alone did not affect in vitro migration. Conclusions—Our data support that CB2R is fundamental for driving neuroblast migration and suggest that an endocannabinoid tone is required for poststroke neurogenesis by promoting neuroblast migration toward the injured brain tissue, increasing the number of new cortical neurons and, conceivably, enhancing motor functional recovery after stroke.
PB American Heart Association
SN 0039-2499, ESSN: 1524-4628
YR 2017
FD 2017-01
LK https://hdl.handle.net/20.500.14352/18075
UL https://hdl.handle.net/20.500.14352/18075
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III (ISCIII) / FEDER
DS Docta Complutense
RD 28 abr 2024