Suppression of CXCL2 upregulation underlies the therapeutic effect of the retinoid Am80 on intracerebral hemorrhage in mice.
J Neurosci Res
; 92(8): 1024-34, 2014 Aug.
Article
en En
| MEDLINE
| ID: mdl-24659080
ABSTRACT
We previously demonstrated that a synthetic retinoic acid receptor agonist, Am80, attenuated intracerebral hemorrhage (ICH)-induced neuropathological changes and neurological dysfunction. Because inflammatory events are among the prominent features of ICH pathology that are affected by Am80, this study investigated the potential involvement of proinflammatory cytokines/chemokines in the effect of Am80 on ICH. ICH induced by collagenase injection into mouse striatum caused prominent upregulation of mRNAs for interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, CXCL1, CXCL2, and CCL3. We found that dexamethasone (DEX) and Am80 differently modulated the increase in expression of these cytokines/chemokines; TNF-α expression was attenuated only by DEX, whereas CXCL2 expression was attenuated only by Am80. Expression of IL-1ß and IL-6 was inhibited both by DEX and Am80. Neurological assessments revealed that Am80, but not DEX, significantly alleviated motor dysfunction of mice after ICH. From these results, we suspected that CXCL2 might be critically involved in determining the extent of motor dysfunction. Indeed, magnetic resonance imaging-based classification of ICH in individual mice revealed that invasion of hematoma into the internal capsule, which has been shown to cause severe neurological disabilities, was associated with higher levels of CXCL2 expression than ICH without internal capsule invasion. Moreover, a CXCR1/2 antagonist reparixin ameliorated neurological deficits after ICH. Overall, suppression of CXCL2 expression may contribute to the beneficial effect of Am80 as a therapeutic agent for ICH, and interruption of CXCL2 signaling may provide a promising target for ICH therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tetrahidronaftalenos
/
Benzoatos
/
Regulación hacia Arriba
/
Hemorragia Cerebral
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Fármacos Neuroprotectores
/
Quimiocina CXCL2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurosci Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón