Gas6 Exerts Neuroprotective Effects via Restoring the Blood-Brain Barrier in Mice with Sepsis-Associated Encephalopathy.

Jul 12, 2023Annals of clinical and laboratory science

Gas6 may protect the brain by repairing the blood-brain barrier in mice with sepsis-related brain dysfunction

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Abstract

Post-septic mice showed increased neurological severity scores and brain edema, but acute treatment with Gas6 improved neurological function.

Sepsis induction in mice resulted in cognitive and emotional impairments.
Gas6 treatment reduced brain edema and improved blood-brain barrier permeability.
The expression of tight junction proteins occludin and zonula occludens-1 was restored following Gas6 treatment.
These findings indicate that Gas6 may protect against the cognitive deficits associated with sepsis.

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OBJECTIVE: Sepsis-associated encephalopathy (SAE), characterized by cognitive and emotional impairments, is not well investigated in sepsis survivors. Growth arrest-specific gene 6 (Gas6) has been extensively used to treat cerebral diseases. This study aimed to evaluate the neuroprotective effects of Gas6 in post-septic mice and to determine the underlying mechanisms of action.

METHODS: Mice underwent cecal ligation and puncture (CLP) for sepsis induction. Mice were then immediately injected with 6 µg of Gas6 via the tail vein, and the effect was evaluated after 24 hours. The neurological severity score (NSS) was used to assess neurological deficits in post-septic mice. In addition, brain edema was evaluated by measuring the brain water content and blood-brain barrier (BBB) permeability using Evans blue (EB) dye extravasation. Western blotting and immunofluorescence assays were performed to determine the expression of tight junction (TJ)-associated proteins such as occludin and zonula occludens-1 (ZO-1).

RESULTS: Post-septic mice exhibited increased NSS, brain edema, and BBB permeability. However, acute Gas6 treatment attenuated the severe effects of sepsis on neurologic function in mice. Therefore, Gas6 attenuates brain edema and restores BBB permeability. These findings suggest that Gas6 could alleviate neurological deficits, brain edema, BBB damage, and reverse the decreased expression of occludin and ZO-1 in the brain tissue to protect against SAE.

CONCLUSION: Gas6 protects against SAE by restoring the impaired BBB permeability.

Gas6 Exerts Neuroprotective Effects via Restoring the Blood-Brain Barrier in Mice with Sepsis-Associated Encephalopathy.

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