<p>Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal</p>

Abstract

Background: As a life-threatening neurological emergency, status epilepticus (SE) is often refractory to available treatment. Current studies have shown a causal role of neuroinflammation in patients with lower seizure thresholds and driving seizures. The ATP-gated purinergic P2X7 receptor (P2X7R) is mainly expressed on the microglia, which function as gatekeepers of inflammation. Although emerging evidence has demonstrated significant anti-inflammatory effects of astaxanthin (AST) in SE, the associated mechanism remains unclear. Therefore, this study aimed to clarify the effects of AST on P2X7R-related inflammation in SE. Methods: SE was induced in rats using lithium-pilocarpine, and AST was administered 1 h after SE induction. Rat microglia were treated with lipopolysaccharide (LPS), AST, ATP, 2,3-O-4-benzoyl-4-benzoyl-ATP (BzATP) and oxidized ATP (oxATP). The Morris water maze, immunohistochemistry, and Nissl staining were performed in rats. Expressions of P2X7R and inflammatory cytokines (such as cycloxygenase-2 (Cox-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) were detected using real-time polymerase chain reaction (RT-PCR) and Western blot (WB) both in rats and microglia. ATP concentration in the microglia was evaluated using ELISA. Results: The AST alleviated hippocampal injury and improved cognitive dysfunction induced by SE. AST also effectively inhibited inflammation and downregulated P2X7R expression in both rat brain and microglia. The results also showed that AST reduced the extracellular ATP levels and that P2X7R expression could be increased by extracellular ATP. In addition, BzATP upregulates the expression of P2X7R and inflammatory factors in microglia. Conversely, it downregulates the expression of P2X7R and inflammatory factors. Conclusion: Our study suggests that AST attenuated ATP-P2X7R mediated inflammation in SE.

Genetic variants of IFIH1 and DHX58 affect the chronicity of hepatitis C in the Chinese Han population

“…AST also effectively inhibits the inflammatory response in the rat brain and down-regulates the expression of P2X7R (ATP-gated purinergic receptor). All these suggest that AST dysfunction and energy metabolism may have a synergistic interaction ( Guazzelli et al, 2019 ; Er et al, 2020 ; Wang et al, 2020 ) which in turn affects the ATP-dependent LGP2 and MDA5 to play a synergistic antiviral effect, but the specific mechanism is not clear and further research is needed.…”

Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human

“…Specifically, translational work in mice and rats suggest that P2XRs could be novel targets for AED development due to epilepsy promoting the upregulation of P2Y6, P2Y12, P2X4, and P2X7 receptors on activated microglia [326,327] and promote neuroinflammation. Specifically, Wang et al recently showed that usage of the anti-inflammatory drug Astaxanthin can attenuate the P2X7R-mediated neuroinflammation that is associated with status epilepticus (SE) [328]. As outlined above, limited release and rapid degradation limit the amount of ATP in the extracellular milieu of healthy brains.…”

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

“…In the same model, a recent study reported that oral treatment with an ATX emulsion to increase its bioavailability improved cognitive function and exhibited antiinflammatory activity by down-regulating inflammation-related proteins such as COX-2, iNOS, TNF-α, IL-6, and IL-1β and increasing IL-10 levels [240]. Furthermore, ATX was effective in attenuating status epilepticus-induced neuroinflammation in rats by suppress-ing extracellular ATP levels and the consequent P2X7R inhibition, a microglial receptor involved in inflammation [241]. The neuroprotective effects of this compound were also evidenced in a model of subarachnoid haemorrhage via inhibition of MMP-9 levels and activity [242] and up-regulation of SIRT1 expression [243].…”