Intranasal Methylprednisolone Effectively Reduces Neuroinflammation in Mice With Experimental Autoimmune Encephalitis

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Relapsing-remitting multiple sclerosis (MS) involves acute neuroinflammatory episodes requiring treatment to prevent disability.
• Current intravenous methylprednisolone therapy for MS relapses is invasive, requires hospitalization, and has limited central nervous system (CNS) penetration.
• Intranasal drug delivery offers a potential alternative for direct CNS treatment with reduced systemic exposure.

Purpose of the Study:

• To evaluate the efficacy of intranasal methylprednisolone for treating neuroinflammation in a mouse model of MS.
• To compare the therapeutic effects of intranasal versus intravenous methylprednisolone administration on neuroinflammation and demyelination.

Main Methods:

• Experimental autoimmune encephalomyelitis (EAE) mice were treated with intranasal or intravenous methylprednisolone.
• Histopathological analysis assessed neuroinflammation, immune cell infiltration, and demyelination in the CNS.
• Expression levels of Iba1, GFAP, and key inflammatory cytokines (IL-1β, IL-6, IL-17, IFN-γ, TNF-α) were measured.

Main Results:

• Intranasal methylprednisolone suppressed the neuroinflammatory peak and reduced CNS immune cell infiltration and demyelination, comparable to intravenous administration.
• Both treatment routes significantly downregulated Iba1 and GFAP expression.
• Intranasal and intravenous methylprednisolone achieved similar reductions in key inflammatory cytokine levels within the spinal cord.
• No nasal cavity damage was observed following intranasal administration.

Conclusions:

• Intranasal delivery of methylprednisolone is a viable and effective alternative for treating neuroinflammation in MS relapses.
• This method demonstrates comparable efficacy to the standard intravenous route while potentially offering improved safety and CNS targeting.
• Intranasal administration presents a promising, non-invasive approach for managing MS relapses directly within the CNS.