Intermittent theta-burst stimulation promotes neurovascular unit remodeling after ischemic stroke in a mouse model

Area of Science:

• Neuroscience
• Neurobiology
• Stroke Research

Background:

• The neurovascular unit is crucial for brain health, but its dysfunction after ischemic stroke leads to nerve-blood vessel uncoupling.
• Intermittent theta-burst stimulation (iTBS) is a transcranial magnetic stimulation technique with potential neuroprotective effects, but its mechanisms are not fully understood.

Purpose of the Study:

• To investigate the therapeutic mechanisms of iTBS in a mouse model of ischemic stroke.
• To explore the impact of iTBS on neurovascular unit function, inflammation, and key signaling pathways.

Main Methods:

• Mice underwent middle cerebral artery occlusion/reperfusion (stroke model).
• Post-stroke, mice were treated with iTBS.
• Neurological function, apoptosis, inflammation, astrocyte-blood vessel coupling, and signaling pathways (PI3K/AKT/GSK3β/β-catenin, NF-κB) were assessed.
• The PI3K inhibitor LY294002 was used to validate the pathway's role.

Main Results:

• iTBS significantly improved neurological function and motor recovery post-stroke.
• iTBS reduced apoptosis in the peri-infarct area and suppressed inflammation.
• iTBS activated the PI3K/AKT/GSK3β/β-catenin pathway and modulated the NF-κB pathway.
• iTBS enhanced A2 astrocyte-blood vessel coupling, an effect reversed by LY294002.

Conclusions:

• iTBS promotes neurovascular unit remodeling and improves outcomes after ischemic stroke in mice.
• The therapeutic effects of iTBS involve modulating microglia and astrocytes via PI3K/AKT/GSK3β and NF-κB signaling.
• iTBS represents a promising non-invasive therapeutic strategy for stroke recovery.