Inflammation plays a key role in the progression of
subarachnoid hemorrhage (SAH). Here, we examined the effects of
astaxanthin (ATX) on the inflammatory response and secondary damage after SAH and the underlying mechanisms of action. In vivo, a prechiasmatic cistern injection model was established in rats and mice. In addition, neuron-microglia cocultures were exposed to
oxyhemoglobin to mimic SAH in vitro. Western blotting revealed that
protein expression of TLR4 was markedly increased in microglia at 24 h after SAH, with consequent increases in the downstream molecules
myeloid differentiation factor 88 and NF-кB. Treatment with ATX significantly inhibited the TLR4 activation, increased
sirtuin 1 expression, and inhibited the subsequent inflammatory response both in vivo and in vitro. ATX also significantly decreased high-mobility group box 1 nuclear translocation and secretion in neurons, an effect that was reversed by the
sirtuin 1-specific inhibitor
sirtinol. ATX administered 4 h after SAH ameliorated cerebral
inflammation, brain edema, and neuronal death and improved neurologic function. ATX reduced neuronal death but did not improve neurologic function in TLR4 knockout mice. These results suggest that ATX reduces the proinflammatory response and secondary
brain injury after SAH, primarily by increasing
sirtuin 1 levels and inhibiting the TLR4 signaling pathway.-Zhang, X., Lu, Y., Wu, Q., Dai, H., Li, W., Lv, S., Zhou, X., Zhang, X., Hang, C., Wang, J.
Astaxanthin mitigates
subarachnoid hemorrhage injury primarily by increasing
sirtuin 1 and inhibiting the
Toll-like receptor 4 signaling pathway.