The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Extended protective effects of three dimensional cultured human mesenchymal stromal cells in a neuroinflammation model

BACKGROUND Human mesenchymal stromal cells(MSCs)possess regenerative potential due to pluripotency and paracrine functions.However,their stemness and immunomod-ulatory capabilities are sub-optimal in conventional two-dimensional(2D)culture.AIM To enhance the efficiency and therapeutic efficacy of MSCs,an in vivo-like 3D culture condition was applied.METHODS MSCs were cultured on polystyrene(2D)or in a gellan gum-based 3D system.In vitro,prostaglandin-endoperoxide synthase 2,indoleamine-2,3-dioxygenase,heme oxygenase 1,and prostaglandin E synthase gene expression was quantified by quantitative real-time polymerase chain reaction.MSCs were incubated with lipopolysaccharide(LPS)-treated mouse splenocytes,and prostaglandin E2 and tumor necrosis factor-alpha levels were measured by enzyme linked immuno-sorbent assay.In vivo,LPS was injected into the lateral ventricle of mouse brain,and MSCs were administered intravenously the next day.Animals were sacrificed and analyzed on days 2 and 6.RESULTS Gellan gum polymer-based 3D culture significantly increased expression of octamer-binding transcription factor 4 and Nanog homeobox stemness markers in human MSCs compared to 2D culture.This 3D environment also heightened expression of cyclooxygenase-2 and heme-oxygenase 1,enzymes known for immunomodulatory functions,including production of prostaglandins and heme degradation,respectively.MSCs in 3D culture secreted more prostaglandin E2 and effectively suppressed tumor necrosis factor-alpha release from LPS-stimulated splenocytes and surpassed the efficiency of MSCs cultured in 2D.In a murine neuroinflammation model,intravenous injection of 3D-cultured MSCs significantly reduced ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression,mitigating chronic inflammation more effectively than 2D-cultured MSCs.CONCLUSION The microenvironment established in 3D culture serves as an in vivo mimetic,enhancing the immunomodulatory function of MSCs.This suggests that engineered MSCs hold significant promise a potent tool for cell therapy.

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies.In this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome.Moreover,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating depression.Additionally,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression.Currently,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment.The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression.Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

Emerging role of galectin 3 in neuroinflammation and neurodegeneration

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

Foeniculum vulgare Mill.inhibits lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in mice.Methods:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA assay.The antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western blotting.For in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic neuroinflammation.Cognitive and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced mice.Results:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(P<0.05).Moreover,LPS-induced oxidative stress and reduced antioxidative enzyme levels were significantly improved by Foeniculum vulgare extract(P<0.05).The extract also regulated the NF-κB/MAPK signaling in BV-2 cells.In an in vivo study,Foeniculum vulgare extract(50,100,and 200 mg/kg)markedly mitigated the LPS-induced cognitive and locomotor impairments in mice.The fingerprinting analysis showed distinctive peaks with rutin,kaempferol-3-O-glucoside,and anethole as identifiable compounds.Conclusions:Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

Maresin 1 alleviates neuroinflammation and cognitive decline in a mouse model of cecal ligation and puncture

Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.

Glymphatic system:a gateway for neuroinflammation

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

Jiaohong pills attenuate neuroinflammation and amyloid-βprotein-induced cognitive deficits by modulating the mitogen-activated protein kinase/nuclear factor kappa-B pathway

Background:Jiaohong pills(JHP)consist of Pericarpium Zanthoxyli(PZ)and Radix Rehmanniae,two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment.However,the precise mechanisms underlying the beneficial effects remain elusive.Here,research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease.Methods:BV-2 cell inflammation was induced by lipopolysaccharide.AD mice were administered amyloid-β(Aβ).Behavioral experiments were used to evaluate learning and memory ability.The levels of nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)were detected using enzymelinked immunosorbent assay(ELISA).The protein expressions of inducible nitric oxide synthase(iNOS)and the phosphorylation level of mitogen-activated protein kinase(MAPK)and nuclear factor kappa-B(NF-κB)were detected using Western blot.Nissl staining was used to detect neuronal degeneration.Results:The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO,IL-1β,TNF-α,and iNOS;increased the expression level of IL-10;and significantly decreased the phosphorylation levels of MAPK and NF-κB.These inhibitory effects were further confirmed in the AD mouse model.Meanwhile,JHP improved learning and memory function in AD mice,reduced neuronal damage,and enriched the Nissl bodies in the hippocampus.Moreover,IL-1βand TNF-αin the cortex were significantly downregulated after JHP administration,whereas IL-10showed increased expression.Conclusions:It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF-κB signaling pathway.

Effect of exogenous free N^(ε)-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction:neuroinflammation,and metabolic disorders

Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.

Garcinia Kola and Kolaviron Attenuates Bisphenol A-Induced Memory Impairment and Hippocampal Neuroinflammation in Male Wistar Rats

Bisphenol A (BPA), a toxicant which can leach into food from plastic containers, is reported to induce neurotoxicity among others via oxidative mechanisms. However, antioxidant compounds have been suggested to mitigate BPA-induced toxicities. Garcinia kola (GK) and its bioactive compound, kolaviron, are well-established natural antioxidants, which can exert protective effects against BPA-induced toxicities. This study was designed to investigate the likely mitigating effect of GK and kolaviron on BPA-induced memory impairment and hippocampal neuroinflammation in male Wistar rats. Thirty-five rats were equally grouped and treated as follows: I and II received distilled water and corn oil, respectively at 0.2 mL, while III - VII received BPA (50 mg/kg), BPA + GK (200 mg/kg), BPA + kolaviron (200 mg/kg), GK and kolaviron, respectively for 28 days p.o. Thereafter, behavioral studies were done using the Novel Object Recognition and Y maze tests. Subsequently under anaesthesia, the hippocampus in each animal was dissected out, homogenized and analysed for malondialdehyde, superoxide dismutase, catalase, reduced glutathione, glutathione transferase, nitrites, interleukin-6, tumour necrosis factor-α, acetylcholinesterase, glutamate acid decarboxylase, and arginase activity. Data were analyzed by ANOVA and Tukey Post-hoc test at p p Garcinia kola and Kolaviron mitigate bisphenol A-induced memory impairment and neuroinflammation via antioxidant potentiation and neurotransmitter balance.

Suppressing neuroinflammation using the near-infrared light emitted by (Sr,Ba)Ga_(12)O_(19): Cr^(3+) phosphor

Neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,affect the elderly worldwide and will become more prevalent as the global population ages.Neuroinflammation is a common characteristic of neurodegenerative diseases.By regulating the phenotypes of microglia,it is possible to suppress neuroinflammation and,in turn,help prevent neurodegenerative diseases.We report a noninvasive photonic approach to regulating microglia from overexcited M1/M2 to the resting M0 phenotype using a special near-infrared(NIR)light emitted by the SrGa_(12)O_(19)∶Cr^(3t) phosphor.The absorbance and internal and external quantum efficiencies of the optimal SreGa_(0.99)Cr_(0.01)_(12)O_(19) phosphor synthesized at 1400℃ for 8 h using 1%H_(3)BO_(3) t 1%AlF3 as flux are 53.9%,99.2%,and 53.5%;the output power and energyconversion efficiency of the LED device packaged using the optimal SrGa_(12)O_(19): Cr^(3+) phosphor driven at 20 mA reach unprecedentedly 19.69 mW and 37.58%,respectively.The broadband emission of the NIR LED device covers the absorption peaks of cytochrome c oxidase well,and the NIR light can efficiently promote the proliferation of microglia,produce adenosine triphosphate(ATP),reverse overexcitation,alleviate and inhibit inflammation,and improve cell survival rate and activity,showing great prospects for photomedicine application.

Astragaloside Ⅳ Protects Against Aβ1-42-induced Oxidative Stress, Neuroinflammation and Cognitive Impairment in Rats

Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms.Methods Adult-male Sprague-Dawley rats(230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test(hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ(5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8 th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior softwaresystem. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-px) and catalase(CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta(IL-1β) and tumor necrosis factor-alpha(TNF-α) in tissue lysates were assayed with ELISA.Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ significantly decreased the levels of IL-1β and TNF-α in the hippocampus of Aβ1-42-induced amnesia’s rats. Conclusion Our findings suggest that AS-Ⅳ might be a useful chemical in improving the spatial memory and relieving the oxidative stress and neuroinflammation in Alzheimer patients.

Exosomes as mediators of neuron-glia communication in neuroinflammation

In recent years,a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological conditions.These nanovesicles (30–150 nm) contain proteins,RNAs and lipids,and their internalization by bystander cells could alter their normal functions.This review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous system.Special emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain,in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative disorders.Given the small size and characteristics of exosomes,they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and neuropathologies.Finally,although the application potential of exosome is still limited,current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation.

Potential therapeutic roles of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease

All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques(aggregated amyloid-beta) and intra-neurofibrillary tangles(hyperphosphorylated tau protein) in the temporal lobe of the brain. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease.

Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson's disease model rats

The present study showed that the latency of rats moving on a vertical grid was significantly prolonged, and the number of rats sliding down from the declined plane was increased remarkably, in rotenone-induced Parkinson＇s disease model rats compared with control rats. The moving latency recovered to normal levels, but the number of slides was significantly increased at 28 days after model establishment. The slope test is a meaningful approach to evaluate the symptoms of Parkinson＇s disease model rats treated with rotenone. In addition, loss of substantia nigral dopaminergic neurons in model rats was observed at 1 day after the model was established, and continued gradually at 14 and 28 days. The expression of tyrosine hydroxylase-positive cells was significantly increased in gastrodin-treated rats at 14 days. Significant numbers of activated microglia cells were observed in model rats at 14 and 28 days; treatment of rats with Madopar at 28 days suppressed microglial activation. Treatment of rats with gastrodin or Madopar at 28 days significantly reduced interleukin-1β expression. The loss of substantia nigral dopaminergic neurons paralleled the microglial activation in Parkinson＇s disease model rats treated with rotenone. The inflammatory factors tumor necrosis factor-a and interleukin-1β are involved in the substantia nigral damage. Gastrodin could protect dopaminergic neurons via inhibition of interteukin-1β expression and neuroinflammation in the substantia nigra.