http://stroke.ahajournals.org/content/48/1/204?etoc=
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Abstract
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-6H-dibenzo[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 vehicle-treated 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.
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