Sansing, Lauren H. and Boisserand, Ligia S. B. (2025) Fingolimod as a Potential Cerebroprotectant- results from the Stroke Preclinical Assessment Network. Stroke. ISSN 1524-4628; 0039-2499

Abstract

ABSTRACT
46 Background:
47 Fingolimod is an immunomodulatory drug used for relapsing Multiple Sclerosis that has
48 shown promising effects in stroke treatment, including improvements in neurofunctional
49 recovery and a reduction in infarct size. Fingolimod modulates the sphingosine-1-
50 phosphate (S1P) receptors, which leads to the internalization of S1P receptors on T and
51 B lymphocytes, thereby attenuating their immune response. Here, we report a secondary
52 analysis from the Stroke Preclinical Assessment Network, a multi-laboratory preclinical
53 trial. We assessed the effects of fingolimod versus vehicle on stroke outcomes to better
54 evaluate its therapeutic potential
55 Methods:
56 The animal population (n = 409) comprised male and female animals treated with
57 fingolimod or vehicle. We used 4 clinically relevant models: young healthy mice (10-12
58 weeks-old (w.o)), aging mice (16+/-1 month-old), obesity induced-hyperglycemic mice
59 (OIH) fed with a high-fat diet for 12 weeks (16 w.o) and spontaneously hypertensive rats
60 (16 +/- 1 w.o). Stroke was induced by the middle cerebral artery occlusion (MCAO) for
61 one hour, followed by reperfusion. Animals received a total of six intraperitoneal injections
62 of 0.5 mg/kg of fingolimod or vehicle. Functional outcomes on turning preference in the
63 corner test and foot-faults while walking on a grid were measured at days 7 and 28. Lesion
64 size and brain morphometry were evaluated at day 2 and day 30 by MRI.
65 Results:
66 Overall, fingolimod did not improve morphological and functional outcomes. However,
67 fingolimod effects varied depending on sex or the comorbidity model. Fingolimod
68 promoted a better outcome in the corner test in aging females. In contrast, it favored a
69 worse outcome in obesity-induced hyperglycemic mice at day 7. Despite having no effect
70 on survival rates or lesion size, fingolimod attenuated the midline retraction at day 30 in
71 aging males, consistent with less atrophy.
72 Conclusion:
73 While fingolimod did not significantly benefit the overall primary functional outcome, its
74 effects varied with sex and comorbidity models, underscoring how the therapeutic
75 potential of a particular drug can differ in a heterogenous population.

Item Type:	Article
Date Deposited:	20 Jan 2026 00:46
Last Modified:	20 Jan 2026 00:46
URI:	https://oak.novartis.com/id/eprint/57522