Abstract
In this work, the sphingosine-1-phosphate receptor modulator fingolimod was assessed as a preclinical candidate for the treatment of acute ischaemic stroke according to the Stroke Therapy Academic Industry Roundtable (STAIR) preclinical recommendations. Young (15–17 weeks), aged (72–73 weeks), and ApoE−/- mice (20–21 weeks) fed a high fat diet (all C57BL/6 mice) underwent permanent electrocoagulation of the left middle cerebral artery. Mice received either saline or fingolimod (0.5 mg/kg or 1 mg/kg) at 2-, 24-, and 48-hours post-ischaemia via intraperitoneal (i.p.) injection. Another cohort of young mice (8–9 and 17–19 weeks) received short-term (5 days) or long-term (10 days) fingolimod (0.5 mg/kg) treatment in a treatment duration study. For young, aged, and ApoE−/- mice, motor behavioural tests (cylinder and grid-walking) were performed at days 0, 3, and 7 post-ischaemia to evaluate neurobehavioural recovery. In the treatment duration study, the grid-walking test was performed at days 0, 2, 5 and 10 post-ischaemia. Brain tissue sections were stained with haematoxylin and eosin (H&E), and NeuN to quantify tissue damage. Flow cytometry was used to quantify T cell populations in blood, spleen, and lymph nodes. The data presented in this article improves our understanding of the potential neuroprotective and immunomodulatory effects of fingolimod in a mouse model of brain ischaemia. Such data may be significant in the design of future preclinical and clinical stroke studies for fingolimod.
Highlights
Histological, behavioural and flow cytometric datasets relating to acute ischaemic stroke in young, aged and ApoE−/− mice in the presence and absence of immunomodulation with fingolimod
The sphingosine-1-phosphate receptor modulator fingolimod was assessed as a preclinical candidate for the treatment of acute ischaemic stroke according to the Stroke Therapy Academic Industry Roundtable (STAIR) preclinical recommendations
The data presented in this article improves our understanding of the potential neuroprotective and immunomodulatory effects of fingolimod in a mouse model of brain ischaemia
Summary
A permanent distal middle cerebral artery occlusion model was performed as previously described [5]. An incision (1 cm) was made to expose the temporal muscle. The temporal muscle was retracted to expose the parietal bones where a small craniotomy was performed. Mice receiving treatment in the Dose Response, Aged, and ApoE studies were dosed at 2-, 24- and 48-hours post–ischaemia. Mice in the dose response study received saline, 0.5 mg/kg or 1 mg/kg fingolimod (Novartis Institutes for Biomedical Research, Switzerland) via i.p. injection. Mice in the Aged and ApoE-/- studies received saline or 0.5 mg/kg fingolimod via i.p. injection. The mice in the treatment duration study received daily injection of either (1) saline, (2) 5 days of fingolimod (0.5 mg/kg) followed by 5 days of saline, or (3) 10 days of fingolimod (0.5 mg/kg). Sham surgeries only involved the incision and retraction of the temporal muscle
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