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J Stroke Cerebrovasc Dis ; 27(11): 3053-3065, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30093209

RESUMEN

BACKGROUND: The present study aimed to examine the protective role of fullerenol nanoparticles against blood-brain barrier (BBB) interruption and brain edema during cerebral ischemia-reperfusion injury probably by reduction of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) transcription. METHODS: The male Wistar rats (weighting 280-320 g) were randomly assigned into four groups as follows: sham, control ischemic, pretreated ischemic, and posttreated ischemic groups. Cerebral ischemia-reperfusion (IR) injury was performed by occlusion of middle cerebral artery (MCA) for 90 minutes followed by twenty-four hours reperfusion. Rats were administered fullerenol 5mg/kg, intraperitoneally, 30 minutes before induction of IR in pretreated ischemic group and immediately after termination of MCA occlusion in posttreated ischemic group. After twenty-four hours reperfusion, the method of Evans blue dye extravasation (EBE) and RT-PCR were used for determination of BBB permeability and mRNA expression levels of MMP-9 and IL-6, respectively. Neuronal deficit score (NDS) and edema of the ischemic hemispheres were also evaluated. RESULTS: MCA occlusion increased NDS in control ischemic rats (3.16 ± 0.16) with concomitant increase in EBE (15.30 ± 3.98µg/g) and edema (3.53 ± 0.50%). Fullerenol in both pretreated and posttreated ischemic groups reduced NDS (36% and 68%, respectively), EBE (89% and 91%, respectively) and edema (53% and 81%, respectively). Although MCA occlusion increased the mRNA expression levels of MMP-9 and IL-6 in ischemic hemispheres, fullerenol in both treatment groups noticeably decreased the mRNA expression levels of these genes. CONCLUSION: In conclusion, fullerenol nanoparticles can protect BBB integrity and attenuate brain edema after cerebral ischemia-reperfusion injury possibly by reduction of IL-6 and MMP-9 transcription.


Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Edema Encefálico/prevención & control , Fulerenos/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Interleucina-6/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Nanopartículas , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/prevención & control , Transcripción Genética/efectos de los fármacos , Animales , Barrera Hematoencefálica/enzimología , Barrera Hematoencefálica/patología , Edema Encefálico/enzimología , Edema Encefálico/genética , Edema Encefálico/patología , Permeabilidad Capilar/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo , Infarto de la Arteria Cerebral Media/enzimología , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/patología , Interleucina-6/genética , Masculino , Metaloproteinasa 9 de la Matriz/genética , Ratas Wistar , Daño por Reperfusión/enzimología , Daño por Reperfusión/genética , Daño por Reperfusión/patología
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