Acute Treatment With Fingolimod Does Not Confer Long-Term Benefit in a Mouse Model of Intracerebral Haemorrhage
| Autor: | Andrea C. Diaz Diaz, Jennifer A. Shearer, Kyle Malone, Christian Waeber |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
lymphocytes
sex differences 0301 basic medicine medicine.medical_treatment Bacterial collagenase 03 medical and health sciences 0302 clinical medicine Atrophy haemorrhagic stroke medicine Pharmacology (medical) cardiovascular diseases Limited evidence Saline sphingosine 1-phosphate Original Research Pharmacology business.industry lcsh:RM1-950 Outcome measures immunomodulator Management of multiple sclerosis medicine.disease Fingolimod lcsh:Therapeutics. Pharmacology 030104 developmental biology Anesthesia Ischemic stroke business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 11 (2021) |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2020.613103 |
| Popis: | Intracerebral haemorrhage (ICH) has no specific treatment, but accounts for up to 15% of all strokes and has the highest mortality. Fingolimod (FTY720) is an immunomodulator approved for the management of multiple sclerosis, with abundant evidence of efficacy in experimental ischemic stroke, and more limited evidence in experimental ICH. The goal of this study was to confirm the efficacy of fingolimod in experimental ICH using rigorous and statistically well-powered studies. ICH was induced in C57BL/6JOlaHsd male and female mice by intrastriatal bacterial collagenase injection. Fingolimod (0.5 mg/kg) or saline was administered intraperitoneally after 0.5, 24 and 72 h, in a randomized and blinded manner. Functional improvement with cylinder, wire hanging, and foot fault tests was evaluated one and two weeks later. Lesion volume and hemispheric atrophy were quantified at the 14-day endpoint. There was a higher mortality in saline-treated females compared to fingolimod-treated females and saline-treated males. There was no treatment- or gender-related difference in the behavioural tests. Histological outcome measures did not differ between any of the groups. These results, contrasting with those of previous studies of fingolimod in experimental ICH, emphasize the importance of rigorous testing of this agent in models more representative of the clinical situation. |
| Databáze: | OpenAIRE |
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