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FTY720 does not protect from traumatic brain injury in mice despite reducing posttraumatic inflammation
Stine Mencl1, Nelli Hennig2, Sarah Hopp1
1Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
Journal of Neuroimmunology
|August 2, 2014
Summary
FTY720, a drug modulating sphingosine-1-phosphate (S1P) receptors, did not improve outcomes in traumatic brain injury (TBI) models. This suggests S1P receptor modulation is not a viable strategy for treating TBI.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Traumatic brain injury (TBI) involves significant inflammation, with lymphocytes playing a key role in lesion development.
- Sphingosine-1-phosphate (S1P) receptor modulators, like FTY720, sequester lymphocytes and show promise in other neurological disease models.
Purpose of the Study:
- To investigate the efficacy of FTY720 in mitigating TBI-induced damage and improving functional outcomes.
- To explore the role of immune cell infiltration in TBI pathogenesis.
Main Methods:
- Mice with focal cortical cryolesions or diffuse brain contusions were treated with FTY720 or vehicle.
- Lesion size, immune cell infiltration (flow cytometry, immunocytochemistry), blood-brain barrier integrity (Evans Blue), and neurological deficits were assessed.
Main Results:
- FTY720 successfully reduced circulating lymphocytes and their infiltration into the injured brain.
- Despite immune cell modulation, FTY720 failed to reduce lesion size or improve neurological function in acute or chronic TBI models.
- Blood-brain barrier disruption and neuronal apoptosis remained unchanged between FTY720-treated and control groups.
Conclusions:
- Pharmacological modulation of S1P receptors is an ineffective therapeutic strategy for traumatic brain injury.
- The study questions the direct pathophysiological relevance of inflammatory cell infiltration in TBI-related neurodegeneration.
