Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats

Abstract

Background: Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neuroprotective effects. This study aimed to investigate the potential therapeutic effects of AST for SCII and the molecular mechanism. Methods: Rat models of SCII with abdominal aortic occlusion for 40 min were carried out to investigate the effects of AST on the recovery of SCII. Tarlov's scores were used to assess the neuronal function; HE and TUNEL staining were used to observe the pathological morphology of lesions. Neuron oxidative stress and inflammation were measured using commercial detection kits. Flow cytometry was conducted to assess the mitochondrial swelling degree. Besides, Western blot assay was used to detect the expression of PI3K/Akt/GSK-3β pathway-related proteins, as well as NOX2 and NLRP3 proteins. Results: The results demonstrated that AST pretreatment promoted the hind limb motor function recovery and alleviated the pathological damage induced by SCII. Moreover, AST significantly enhanced the antioxidative stress response and attenuated mitochondrial swelling. However, AST pretreatment hardly inhibited the levels of proinflammatory cytokines after SCII. Most importantly, AST activated p-Akt and p-GSK-3β expression levels. Meanwhile, cotreatment with LY294002 (a PI3K inhibitor) was found to abolish the above protective effects observed with the AST pretreatment. Conclusion: Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3β pathway.

MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat

“…Finally, the high power fields of spinal cord were randomly selected, and average percentage in three sections/rat of TUNEL-positive cells to total nuclei were calculated by two blind investigators using ImageJ software (Download from the NIH website 2 ). The apoptotic rate was calculated as AR = (number of TUNEL-positive cells/total number of nuclei) × 100% ( Fu et al, 2020 ).…”

Sevoflurane pretreatment regulates abnormal expression of MicroRNAs associated with spinal cord ischemia/reperfusion injury in rats

“…As one of the most serious spinal cord complications, SCII generally results from spinal cord injuries or thoracoabdominal aortic surgery and may lead to paralysis or paraplegia and neurologic deficits [1,2]. However, the molecular mechanisms underlying the development of SCII are not well understood.…”

“…Spinal cord ischemia/reperfusion injury (SCII) is a serious spinal injury that generally arises from ischemia in spinal cord tissues (1). Severe complications can result from SCII, including paralysis or paraplegia, with the incidence of paraplegia being as high as 14% (2). To date, there are no effective interventions for the prevention and treatment of SCII given the multiple pathological factors, including oxidative stress, blood spinal cord barrier (BSCB), inflammation, apoptosis, and autophagy involved in the development of SCII (3,4).…”

Astaxanthin: The possible effects of this carotenoid on disease, inflammation and aging control. A meta-analysis

“…The ability of ATX to decrease inflammatory processes as well as reduce free radicals has been extensively reported in scientific literature. In our present review we found several studies in animals and humans where ATX had remarkable results in enzymes activity such as SOD [31,32,33] , GPx [27,34] , transcription factor signaling proteins such as AMPK [33] , control of inflammatory processes by inhibiting NF-kβ [35] , TNF-α [36,37] among others. These markers appeared four or more times in published in vivo works found in this review.…”