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.
Highlights
Spinal cord injury (SCI) is associated with several temporary or permanent pathological changes resulting in loss of physiological nervous function [1]
In order to determine the systemic levels of ALA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), we examined the blood plasma of animals that received injections of PUFA n3 or vehicle (Lipo MCT) emulsions and compared them to basal levels obtained from control animals
According to our previous timeline study, inflammasome components are up-regulated with a peak at 72 h post SCI, the effect of PUFA n3 on inflammasomes was determined at this time point (Figure 3) [6]
Summary
Spinal cord injury (SCI) is associated with several temporary or permanent pathological changes resulting in loss of physiological nervous function [1]. The pathological changes of SCI involve primary and secondary damage. The primary injury results from the initial insult and is characterized by destruction of neural tissue and blood vessels, whereas the secondary phase starts after a few minutes and lasts for weeks post the mechanical injury and is identified with an extensive neurological injury such as oxidative stress, ischemia, and inflammation [2]. Neuroinflammation is one of the principal factors in the pathogenesis of SCI which is mainly mediated by the activation of immune cells (such as macrophages/microglia) [3]. After SCI, immune cells are activated and subsequently secrete a series of proinflammatory cytokines to recruit blood-borne leukocytes to the injured site. Most inflammasomes consist of a sensor protein: NOD-like receptor (NLR), an adapter molecule: apoptosisassociated speck-like protein containing a Caspase-recruitment domain (ASC, known as Pycard), and an enzymatic component: Caspase 1 (CASP1). It has been shown that activation of inflammasomes such as NLR Family Pyrin Domain Containing 3 (NLRP3)
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