Fingolimod prevents cognitive impairments following hypoxia-induced neonatal seizure by ameliorating the inflammation and oxidative stress in male and female juvenile rats

Hajipour, Somayeh; Shooshtari, Maryam Khombi; Farbood, Yaghoob; Mard, Seyed Ali; Sarkaki, Alireza; Chameh, Homeira Moradi; Karampour, Neda Sistani; Ghafouri, Samireh

doi:10.1016/j.lmot.2023.101874

Cited by 3 publications

(1 citation statement)

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“…In conclusion, ngolimod reduces in ammation, excitotoxicity, glial activation and polarization, and BBB destruction, and improves neurogenesis [42]. For all these reasons, ngolimod has a bene cial effect on different neurological disorders such as stroke [42], hypoxia [43], and epilepsy [44], [45], [46], [47].…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of fingolimod in a Lafora disease mouse model by preventing reactive astrogliosis-derived neuroinflammation and brain infiltration of T-lymphocytes.

Rubio

Campos-Rodríguez

Sanz

2023

Preprint

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Lafora disease (LD; OMIM#254780) is a rare, devastating, and fatal form of progressive myoclonus epilepsy that affects young adolescents and has no treatment yet. One of the hallmarks of the disease is the accumulation of aberrant poorly branched forms of glycogen (polyglucosans, PGs) in the brain and peripheral tissues. The current hypothesis is that this accumulation is causative of the pathophysiology of the disease. Another hallmark of LD is the presence of neuroinflammation. We have recently reported the presence of reactive glia-derived neuroinflammation in LD mouse models and defined the main inflammatory pathways that operate in these mice, mainly TNF and IL-6 signaling pathways. In addition, we described the presence of infiltration of peripheral immune cells in the brain parenchyma, which could cooperate and aggravate the neuroinflammatory landscape of LD. In this work, we have checked the beneficial effect of two compounds with the capacity to ameliorate neuroinflammation and reduce leukocyte infiltration into the brain, namely fingolimod and dimetylfumarate. Our results indicate a beneficial effect of fingolimod in reducing reactive astrogliosis-derived neuroinflammation and T-lymphocyte infiltration, which correlated with the improved behavioral performance of the treated Epm2b-/- mice. On the contrary, dimethylfumarate, although it was able to reduce reactive astrogliosis, was less effective in preventing neuroinflammation and T-lymphocyte infiltration and in modifying behavioral tests.

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