Administration of Δ9-Tetrahydrocannabinol Following Controlled Cortical Impact Restores Hippocampal-Dependent Working Memory and Locomotor Function.
Cannabis Cannabinoid Res
; 7(4): 424-435, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-34747647
ABSTRACT
Hypothesis:
Administration of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum. Materials andMethods:
C57BL/6J mice underwent CCI and were treated for 3 days with Δ9-THC 3 mg/kg intraperitoneally (i.p.). Short-term working memory was determined using the spontaneous alternations test during exploratory behavior in a Y-maze. Locomotor function was measured as latency to fall from a rotating drum (rotometry). These behaviors were recorded at baseline and 3, 7, and 14 days after CCI. Groups of mice were euthanized at 7 and 14 days. Extent of microgliosis, astrocytosis, and G-CSF, BDNF, and GDNF expression were measured at 7 and 14 days in cerebral cortex, striatum, and HP on the side of the trauma. Levels of the most abundant endocannabinoid (2-arachidonoyl-glycerol [2-AG]) was also measured at these times.Results:
Δ9-THC-treated mice exhibited marked improvement in performance on the Y-maze indicating that treatment with the phytocannabinoid could reverse the deficit in working memory caused by the CCI. Δ9-THC-treated mice ran on the rotarod longer than vehicle-treated mice and recovered to normal rotarod performance levels at 2 weeks. Δ9-THC-treated mice, compared with vehicle-treated animals, exhibited significant upregulation of G-CSF as well as BDNF and GDNF in the cerebral cortex, striatum, and HP. Levels of 2-AG were also increased in the Δ9-THC-treated mice.Conclusion:
Administration of the phytocannabinoid Δ9-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dronabinol
/
Lesões Encefálicas Traumáticas
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article