101. The effect of astrocyte-derived fatty acid-binding protein 7 on blood-brain barrier breakdown in LPS-induced sepsis in mice.
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Altunsu, Deniz, Ayvaz, Ecem, Temizyürek, Arzu, Kaya, Mehmet, and Ahıshalı, Bülent
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FATTY acid-binding proteins , *BLOOD-brain barrier , *BRAIN physiology , *SEPSIS , *BLOOD circulation , *LIPID rafts , *BODY temperature regulation , *HOMEOSTASIS - Abstract
Objective: Sepsis is a life-threatening condition involving systemic abnormalities caused by exogenous factors including lipopolysaccharide (LPS) derived from pathogens and endogenous factors released by the host cells. Sepsis severely affects the function of various organs including brain in response to systemic inflammation. Barrier-type brain capillary endothelial cells play a vital role in maintaining neuronal homeostasis by regulating the trafficking of substances between blood circulation and brain parenchyma. Fatty acid-binding protein 7 (FABP7) involves in astrocytic differentiation and migration and supports vascular regeneration in the damaged brain. Moreover, it regulates the formation of caveolae, a specific lipid raft functioning in molecular transport across plasmalemma. Methods: To investigate the effect of exogenous FABP7 administration on sepsis-induced BBB disruption, the control group was injected with % 0.9 saline (n=6) and the septic mice model was obtained by single dose LPS (n=6, 3 mg/kg). One hour later, these mice were treated with FABP7 at 40 or 80 μg/kg doses (n=6). As a BBB tracer, Alexa-fluor albumin 594 was injected at 23 h and allowed to circulate for one hour. Results: LPS increased body temperature, whereas, in these animals, a high dose of FABP7 yielded a decrease from 41°C to 37 °C (p<0.05). LPS increased serum procalcitonin level which was decreased by 80 μg/kg FABP7 (p<0.05). Moreover, a significant increase in BBB permeability to the tracer was observed by LPS and 80 μg/kg FABP7 administration significantly reversed the BBB breakdown (p<0.05). In addition, LPS severely triggered anxiety-like behavior, which was significantly alleviated following 80 μg/kg FABP7 (p<0.05). Conclusion: In conclusion, our data show that FABP7 administration may be used as a novel therapeutic approach in the treatment of sepsis-related BBB disruption. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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