Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice

Urolithin A (UA) is a natural metabolite produced from polyphenolics in foods such as pomegranates, berries, and nuts. UA is neuroprotective against Parkinson's disease, Alzheimer's disease, and cerebral hemorrhage. However, its effect against traumatic brain injury remains unknown. In this study, we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA. We found that UA greatly reduced brain edema; increased the expression of tight junction proteins in injured cortex; increased the immunopositivity of two neuronal autophagy markers, microtubule-associated protein 1A/B light chain 3A/B (LC3) and p62; downregulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR), two regulators of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway; decreased the phosphorylation levels of inhibitor of NF kappa B (I kappa B) kinase alpha (IKK alpha) and nuclear factor kappa B (NF kappa B), two regulators of the neuroinflammation-related Akt/IKK/NF kappa B signaling pathway; reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex; and improved mouse neurological function. These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury, and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NF kappa B signaling pathways, thus reducing neuroinflammation and enhancing autophagy.

Automated summary

Urolithin A (UA), a natural metabolite, has neuroprotective effects. This study showed that UA decreased brain edema, increased tight junction protein expression, and promoted neuronal autophagy. In addition, UA reduced neuroinflammation by inhibiting two signaling pathways and improved neurological function in mice.