Synaptamide modulates glial and neurotransmitter activity in the spinal cord during neuropathic pain.

N-docosahexaenoylethanolamine, or synaptamide, is an endogenous metabolite of docosahexaenoic acid that is known for synaptogenic and neurogenic effects. In our previous studies we have shown that synaptamide attenuates neuropathic pain, facilitates remyelination, and reduces neuroinflammation after the chronic constriction injury (CCI) of the sciatic nerve in rats. In the current study, we show that daily synaptamide administration (4 mg/kg/day) within 14 days post-surgery: (1) decreases micro- and astroglia activity in the dorsal and ventral horns of the lumbar spinal cord; (2) modulates pro-inflammatory (IL1β, IL6) and anti-inflammatory (IL4, IL10) cytokine level in the serum and spinal cord; (3) leads to a rise in synaptamide and anandamide concentration in the spinal cord; (4) enhances IL10, CD206 and N-acylethanolamine-hydrolyzing acid amidase synthesis in macrophage cell culture following LPS-induced inflammation.

Effect of Oleoylethanolamide-Based Dietary Supplement on Systemic Inflammation in the Development of Alimentary-Induced Obesity in Mice.

The complex effect of oleoylethanolamide-based dietary supplement (OEA-DS) was studied in a model of diet-induced obesity in mice. Physiological, biochemical, and immunohistochemical methods were used to reveal differences in the changes in the weight of experimental animals, morphological changes in the spleen tissues, and changes in the cytokine expression profile in the spleen, blood plasma, and macrophage cell culture. First, it is shown that a hypercaloric diet high in carbohydrates and cholesterol led to the development of systemic inflammation, accompanied by organ morphological changes and increased production of proinflammatory cytokines.

Anti-inflammatory Effect of Polyunsaturated Fatty Acid N-Acylethanolamines Mediated by Macrophage Activity In Vitro and In Vivo.

In recent years, there has been increasing interest in studying the anti-inflammatory activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines, NAE), which are highly active lipid mediators. The results of this study demonstrate that a dietary supplement (DS) of fatty acid-derived NAEs reduces LPS-induced inflammation. The processes of cell proliferation, as well as the dynamics of Iba-1-, CD68-, and CD163-positive macrophage activity within the thymus and spleen were studied.

Fatty Acid-Derived -acylethanolamines Dietary Supplementation Attenuates Neuroinflammation and Cognitive Impairment in LPS Murine Model.

Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of neuropathology and generalized inflammatory processes. -acylethanolamine (NAE) derivatives of fatty acids, being highly active lipid mediators, possess pro-resolving activity in inflammatory processes and are promising agents for the suppression of neuroinflammation and its consequences.

Synaptamide Modulates Astroglial Activity in Mild Traumatic Brain Injury.

At present, the study of the neurotropic activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines) is becoming increasingly important. N-docosahexaenoylethanolamine (synaptamide, DHEA) is a highly active metabolite of docosahexaenoic acid (DHA) with neuroprotective, synaptogenic, neuritogenic, and anti-inflammatory properties in the nervous system. Synaptamide tested in the present study was obtained using a chemical modification of DHA isolated from squid liver.

Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain.

The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX.

Mild Traumatic Brain Injury Contributes to the Development of Delayed Neuroinflammation.

Introduction: In recent years, according to the literature, the problem of mild traumatic brain injury (mTBI) has become more and more urgent. Compared to moderate to severe craniocerebral trauma, mTBI occurs in a far greater number of people. The delayed sequelae caused by a single mTBI or multiple mTBIs are a significant public health problem.

Chimyl Alcohol Exhibits Proinflammatory Activity in vivo and in vitro.

Marine organisms are among the prominent and abundant sources of 1-O-alkyl-sn-glycerols, including chimyl alcohol (CA), batyl alcohol and selachyl alcohol. These biologically active compounds are precursors in plasmalogen and phospholipid biosynthesis, which are the main irreplaceable components of cell membranes. The results of this study demonstrate that CA promotes the activation of immune processes in the mouse spleen and in the mouse macrophage cell culture RAW 264.

N-docosahexaenoylethanolamine reduces neuroinflammation and cognitive impairment after mild traumatic brain injury in rats.

At present, there is a growing interest in the study of the neurotropic activity of polyunsaturated fatty acids ethanolamides (N-acylethanolamines). N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endogenous metabolite and structural analogue of anandamide, a widely studied endocannabinoid derived from arachidonic acid. The results of this study demonstrate that DHEA, when administered subcutaneously (10 mg/kg/day, 7 days), promotes cognitive recovery in rats subjected to mild traumatic brain injury (mTBI).

-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury.

Chronic neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in pain pathogenesis. One of the factors underlying chronic neuropathic pain is neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release. -docosahexaenoylethanolamine (DHEA, synaptamide) is an endocannabinoid-like metabolite synthesized endogenously from docosahexaenoic acid.

Hippocampal Neurogenesis in Conditions of Chronic Stress Induced by Sciatic Nerve Injury in the Rat.

The dentate gyrus of the hippocampus is the primary location of adult neurogenesis, which is affected by a variety of external and internal factors, including activity of surrounding glial cells. This study concerns alterations in hippocampal neurogenesis and changes in activity of both proinflammatory and neuroprotective microglia/macrophages after sciatic nerve injury in the rat. Here, we demonstrated that the chronic pain induced by a peripheral nerve injury manifests in the hippocampus by a decrease in proliferation (PCNA+) and neurogenesis (DCX+), an increase in proinflammatory cytokines (CD86+), and a reduction in neuroprotective (CD163+) microglia/macrophages.

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in vitro.

The majority of modern treatment methods for malignant brain tumors are not sufficiently effective, with a median survival time varying between 9 and 14 months. Metastatic and invasive processes are the principal characteristics of malignant tumors. The most important pathogenic mechanism is epithelial‑mesenchymal transition (EMT), which causes epithelial cells to become more mobile, and capable of invading the surrounding tissues and migrating to distant organs.

Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review).

Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and ~20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy.