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Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H2O2 evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new "green" carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations. [ABSTRACT FROM AUTHOR]

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin's ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1. [ABSTRACT FROM AUTHOR]

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin’s ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1.

To counteract oxidative stress and associated brain diseases, antioxidant systems rescue neuronal cells from oxidative stress by neutralizing reactive oxygen species and preserving gene regulation. It is necessary to understand the communication and interactions between brain cells, including neurons, astrocytes and microglia, to understand oxidative stress and antioxidant mechanisms. Here, the role of glia in the protection of neurons against oxidative injury and glia–neuron crosstalk to maintain antioxidant defense mechanisms and brain protection are reviewed. The first part of this review focuses on the role of glia in the morphological and physiological changes required for brain homeostasis under oxidative stress and antioxidant defense mechanisms. The second part focuses on the essential crosstalk between neurons and glia for redox balance in the brain for protection against oxidative stress.

Protocatechuic acid (PCA) was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI)-induced neuronal death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes neuronal death in the hippocampus and cerebral cortex. The present study aimed to evaluate the therapeutic potential of PCA on TBI-induced neuronal death. Here, TBI was induced by a controlled cortical impact model using rats. PCA (30 mg/kg) was injected into the intraperitoneal (ip) space immediately after TBI. Neuronal death was evaluated with Fluoro Jade-B (FJB) staining at 24 h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE), glutathione (GSH) concentration was analyzed by glutathione adduct with N-ethylmaleimide (GS-NEM) staining at 24 h after TBI, and microglial activation in the hippocampus was detected by CD11b immunohistochemistry at one week after TBI. We found that the proportion of degenerating neurons, oxidative injury, GSH depletion, and microglia activation in the hippocampus and cortex were all reduced by PCA treatment following TBI. Therefore, our study suggests that PCA may have therapeutic potential in preventing TBI-induced neuronal death. [ABSTRACT FROM AUTHOR]

Epileptic seizures are short episodes of abnormal brain electrical activity. Many survivors of severe epilepsy display delayed neuronal death and permanent cognitive impairment. Donepezil is an acetylcholinesterase inhibitor and is an effective treatment agent for Alzheimer's disease. However, the role of donepezil in seizure-induced hippocampal injury remains untested. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25 mg/kg). Donepezil (2.5 mg/kg/day) was administered by gavage in three different settings: (1) pretreatment for three days before the seizure; (2) for one week immediately after the seizure; and (3) for three weeks from three weeks after the seizure. We found that donepezil showed mixed effects on seizure-induced brain injury, which were dependent on the treatment schedule. Pretreatment with donepezil aggravated neuronal death, oxidative injury, and microglia activation. Early treatment with donepezil for one week showed neither adverse nor beneficial effects; however, a treatment duration of three weeks starting three weeks after the seizure showed a significant reduction in neuronal death, oxidative injury, and microglia activation. In conclusion, donepezil has therapeutic effects when injected for three weeks after seizure activity subsides. Therefore, the present study suggests that the therapeutic use of donepezil for epilepsy patients requires a well-conceived strategy for administration. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes.

Salmonella typhimurium cells were subjected to pulsed electric field (PEF) treatment at 25 kV/cm for 0-4 ms to investigate the effect of PEF on the cytoplasmic membrane lipids and oxidative injury of cells. Results indicated that PEF treatment induced a decrease of membrane fluidity of Salmonella typhimurium (S. typhimuriumi), possibly due to the alterations of fatty acid biosynthesis-associated gene expressions (down-regulation of cfa and fabA gene expressions and the up-regulation of fabD gene expression), which, in turn, modified the composition of membrane lipid (decrease in the content ratio of unsaturated fatty acids to saturated fatty acids). In addition, oxidative injury induced by PEF treatment was associated with an increase in the content of malondialdehyde. The up-regulation of cytochrome bo oxidase gene expressions (cyoA, cyoB, and cyoC) indicated that membrane damage was induced by PEF treatment, which was related to the repairing mechanism of alleviating the oxidative injury caused by PEF treatment. Based on these results, we achieved better understanding of microbial injury induced by PEF, suggesting that micro-organisms tend to decrease membrane fluidity in response to PEF treatment and, thus, a greater membrane fluidity might improve the efficiency of PEF treatment to inactivate micro-organisms. [ABSTRACT FROM AUTHOR]

To counteract oxidative stress and associated brain diseases, antioxidant systems rescue neuronal cells from oxidative stress by neutralizing reactive oxygen species and preserving gene regulation. It is necessary to understand the communication and interactions between brain cells, including neurons, astrocytes and microglia, to understand oxidative stress and antioxidant mechanisms. Here, the role of glia in the protection of neurons against oxidative injury and glia–neuron crosstalk to maintain antioxidant defense mechanisms and brain protection are reviewed. The first part of this review focuses on the role of glia in the morphological and physiological changes required for brain homeostasis under oxidative stress and antioxidant defense mechanisms. The second part focuses on the essential crosstalk between neurons and glia for redox balance in the brain for protection against oxidative stress. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes. [ABSTRACT FROM AUTHOR]

Protocatechuic acid (PCA) was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI)-induced neuronal death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes neuronal death in the hippocampus and cerebral cortex. The present study aimed to evaluate the therapeutic potential of PCA on TBI-induced neuronal death. Here, TBI was induced by a controlled cortical impact model using rats. PCA (30 mg/kg) was injected into the intraperitoneal (ip) space immediately after TBI. Neuronal death was evaluated with Fluoro Jade-B (FJB) staining at 24 h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE), glutathione (GSH) concentration was analyzed by glutathione adduct with N -ethylmaleimide (GS-NEM) staining at 24 h after TBI, and microglial activation in the hippocampus was detected by CD11b immunohistochemistry at one week after TBI. We found that the proportion of degenerating neurons, oxidative injury, GSH depletion, and microglia activation in the hippocampus and cortex were all reduced by PCA treatment following TBI. Therefore, our study suggests that PCA may have therapeutic potential in preventing TBI-induced neuronal death., Competing Interests: The authors declare no conflict of interest.

Salmonella typhimurium cells were subjected to pulsed electric field (PEF) treatment at 25 kV/cm for 0-4 ms to investigate the effect of PEF on the cytoplasmic membrane lipids and oxidative injury of cells. Results indicated that PEF treatment induced a decrease of membrane fluidity of Salmonella typhimurium (S. typhimuriumi), possibly due to the alterations of fatty acid biosynthesis-associated gene expressions (down-regulation of cfa and fabA gene expressions and the up-regulation of fabD gene expression), which, in turn, modified the composition of membrane lipid (decrease in the content ratio of unsaturated fatty acids to saturated fatty acids). In addition, oxidative injury induced by PEF treatment was associated with an increase in the content of malondialdehyde. The up-regulation of cytochrome bo oxidase gene expressions (cyoA, cyoB, and cyoC) indicated that membrane damage was induced by PEF treatment, which was related to the repairing mechanism of alleviating the oxidative injury caused by PEF treatment. Based on these results, we achieved better understanding of microbial injury induced by PEF, suggesting that micro-organisms tend to decrease membrane fluidity in response to PEF treatment and, thus, a greater membrane fluidity might improve the efficiency of PEF treatment to inactivate micro-organisms.