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Caloric Restriction Preserves BBB Integrity After Transient Focal Cerebral Ischemia Through Reducing Neutrophil
Chenran Wang1, Leilei Mao1, Miao He1
1Department of Anesthesiology of Eye & Ent Hospital, Department of Anesthesiology of Obstetrics & Gynecology Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, China.
Restricted feeding (RF) protects brain white and gray matter after ischemic stroke by maintaining blood-brain barrier integrity. This neuroprotection is partly achieved by reducing neutrophil infiltration, offering a basis for stroke treatment.
Area of Science:
- Neuroscience
- Ischemic Stroke Research
- Dietary Interventions
Background:
- Caloric restriction (CR) is known to promote health and protect brain matter from ischemic stroke.
- Understanding the precise mechanisms of restricted feeding (RF) is crucial for developing targeted stroke therapies.
Purpose of the Study:
- To investigate the neuroprotective mechanisms of RF following transient focal cerebral ischemia (tFCI).
- To establish a theoretical foundation for precise clinical treatments of stroke using dietary interventions.
Main Methods:
- C57BL/6J mice were pretreated with 70% RF for 28 days before tFCI.
- Neuroprotection was assessed using histology, diffusion tensor imaging (DTI), and behavioral tests.
- Brain inflammation, blood-brain barrier (BBB) integrity, and neutrophil infiltration were evaluated using various molecular and imaging techniques.
Main Results:
- RF significantly reduced gray and white matter injury and neurological deficits post-tFCI.
- RF suppressed brain inflammation, decreasing pro-inflammatory cytokines and chemokines.
- RF enhanced BBB integrity by reducing neutrophil and macrophage infiltration and matrix metalloprotein-9 release.
Conclusions:
- Restricted feeding (RF) confers neuroprotection against ischemic stroke by preserving blood-brain barrier integrity.
- Reduced neutrophil infiltration is a key mechanism underlying RF's protective effects.
- These findings support RF as a potential therapeutic strategy for stroke patients.
