Multiple sclerosis and related disorders · 2022
Intranasal administration of fingolimod (FTY720) attenuates demyelination area in lysolecithin-induced demyelination model of rat optic chiasm.
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Ghasemi-Kasman Maryam, Nosratiyan Nasrin, Hashemian Mona, Ahmadian Seyyed-Raheleh, Parsian Hadi, Rostami-Mansoor Sahar
Аннотация
BACKGROUND: Fingolimod (FTY720) is an oral immunosuppressive compound that has been prescribed to multiple sclerosis (MS) patients since 2010. The lipophilicity and low molecular weight of FTY720 allows it to cross blood brain barrier (BBB) and exert both peripheral and central effects. Previous reports showed that intranasal (IN) administration of drugs are the preferred non-invasive route, which bypasses BBB and improves their delivery and bioavailability in the central nervous system (CNS). Therefore, we aimed to compare the effects of IN and oral administrations of FTY720 on astrocyte activation and demyelination levels of optic chiasm in a focal demyelination model.
METHODS: The experimental model was induced by injection of 2 µL lysolecithin 1% into the optic chiasm of male Wistar rats. The rats were treated by oral gavage or intranasal drop of FTY720 at dose of 0.3 mg/kg for 14 days. Astrocyte activation was analyzed using GFAP immunostaining, extent of demyelination, and myelination levels were measured by fluoromyelin staining, and MOG immunostaining, respectively. Then, the concentration of FTY720 was measured by high performance liquid chromatography (HPLC) method in brain tissues.
RESULTS: Our data showed that IN administration of FTY720 significantly decreases astrocyte activation and demyelination levels in the optic chiasm compared to the oral administration route. In addition, the concentration of FTY720 was higher in the brain tissue of IN receiving rats compared to the oral treated group.
CONCLUSION: It seems that IN administration of FTY720 may be a preferred route to decline the central inflammation and demyelination levels in the MS patients.
METHODS: The experimental model was induced by injection of 2 µL lysolecithin 1% into the optic chiasm of male Wistar rats. The rats were treated by oral gavage or intranasal drop of FTY720 at dose of 0.3 mg/kg for 14 days. Astrocyte activation was analyzed using GFAP immunostaining, extent of demyelination, and myelination levels were measured by fluoromyelin staining, and MOG immunostaining, respectively. Then, the concentration of FTY720 was measured by high performance liquid chromatography (HPLC) method in brain tissues.
RESULTS: Our data showed that IN administration of FTY720 significantly decreases astrocyte activation and demyelination levels in the optic chiasm compared to the oral administration route. In addition, the concentration of FTY720 was higher in the brain tissue of IN receiving rats compared to the oral treated group.
CONCLUSION: It seems that IN administration of FTY720 may be a preferred route to decline the central inflammation and demyelination levels in the MS patients.