Regulation of Inflammasomes by Application of Omega-3 Polyunsaturated Fatty Acids in a Spinal Cord Injury Model

Abstract

Omega-3 polyunsaturated fatty acids (PUFA n3) ameliorate inflammation in different diseases and potentially improve neurological function after neuronal injury. Following spinal cord injury (SCI), inflammatory events result in caspase-1 mediated activation of interleukin-1 beta (IL-1b) and 18. We aim to evaluate the neuroprotective potency of PUFA n3 in suppressing the formation and activation of inflammasomes following SCI. Male Wistar rats were divided into four groups: control, SCI, SCI+PUFA n3, and SCI+Lipofundin MCT (medium-chain triglyceride; vehicle). PUFA n3 or vehicle was intravenously administered immediately after SCI and every 24 h for the next three days. We analyzed the expression of NLRP3, NLRP1, ASC, caspase-1, IL-1b, and 18 in the spinal cord. The distribution of microglia, oligodendrocytes, and astrocytes was assessed by immunohistochemistry analysis. Behavioral testing showed significantly improved locomotor recovery in PUFA n3-treated animals and the SCI-induced upregulation of inflammasome components was reduced. Histopathological evaluation confirmed the suppression of microgliosis, increased numbers of oligodendrocytes, and the prevention of demyelination by PUFA n3. Our data support the neuroprotective role of PUFA n3 by targeting the NLRP3 inflammasome. These findings provide evidence that PUFA n3 has therapeutic effects which potentially attenuate neuronal damage in SCI and possibly also in other neuronal injuries.

Lycium Barbarum Glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs/NF-kB and pyroptosis pathways.

“…Previous studies have shown that the unsaturated fatty acid DHA can inhibit NLRP3 and other key proteins of pyroptosis [25]. Unsaturated fatty acids reduce injury-related oxidative stress, decrease microglia/macrophage responses, and improve motor function and bladder function recovery in rats [42]. Following entry into the brain, DHA is esterified into and recycled amongst membrane phospholipids contributing the distribution of DHA in brain phospholipids.…”

Ferroptosis is a new therapeutic target for spinal cord injury

“…It has been shown that the spinal cord contains high levels of polyunsaturated fatty acids, which have been shown to be involved in the oxidative stress response following SCI ( Baazm et al, 2021 ). Studies on the regulation of SCI by unsaturated fatty acids such as short-chain fatty acids (SCFA) have been widely reported in recent years ( Filippone et al, 2020 ).…”

“…Aerobic oxidation, glucose metabolism and lipid metabolism play a crucial role in life activities, all three being interconnected and independent of each other. The role of lipid metabolism in Ferroptosis has been widely reported ( Baazm et al, 2021 ). In contrast, the role of aerobic oxidation and sugar metabolism in Ferroptosis has hardly been reported.…”

“…Secondary injury is a cascade amplification response triggered by primary injury, which is divided into three stages: acute, subacute, and chronic injury, manifested as post-traumatic inflammatory response, free radical formation, and PCD of cells ( Alcántar-Garibay et al, 2022 ). While PCD includes autophagy, necroptosis, cell scorching, and Ferroptosis, among others ( Li et al, 2022 ), and it has been recently demonstrated that iron overload ( Gong et al, 2022 ), ROS accumulation ( Feng et al, 2021 ), lipid peroxidation ( Baazm et al, 2021 ), and glutamate accumulation ( Zhao et al, 2022 ) associated with Ferroptosis are all present in SCI, it is therefore suggested that Ferroptosis may be involved in the pathological process of secondary injury associated with SCI.…”

Perspective Chapter: Pathophysiology of Spinal Cord Injury and Effect of Neutraceuticals in Providing Potential Health Benefits

“…Study by Baazm et al [61] states that omega-3 fatty acid supplementation supports neurological function in the event of neuronal injury and suppresses the activity of inflammatory markers.…”