42 results about "Microglial cell activation" patented technology

Treatment of microglial cells with nicotine and THC synergistically attenuate the microglial activation. Using microglial activation, the combination of THC and nicotine interact synergistically reduced LPS induced TNF-α release, showing that the combination of THC and nicotine clinically have greater efficacy in reducing neuroinflammation with less side effects than either drug given alone. CD40 signaling was found critically involved in pathological activation of microglial cells. This invention is also relevant to peripheral inflammation as well thru macrophages. In addition, other cannabinoids and other nicotinic-like medications currently in development are also covered under this discovery.

The present invention provides assays to identify compounds that affect microglial cell activation, and specifically assays to identify compounds that affect secretion of cytokines from these microglial cells by modulating PGE2-mediated activity. The assays of the invention include assays for testing microglial cell activation by contacting microglia with compounds that modulate β-amyloid PGE2-mediated activation, which can be identified by cellular activity such as secretion of cytokines, e.g., TNF-α and IL-1α,. The effect of the candidate compound can be determined by comparing the effect with a control culture which is not contacted with the compound, or by comparing the effect with a standardized profile.

The present invention relates to a composition comprising the purified extract of bee venom for preventing and treating degenerative brain diseases and the use thereby. The purified extract of bee venom shows potent inhibitory effect on microglial cell activation and abnormal circling behavior using by animal model of degenerative brain disease as well as potent cell-protective activity therefore, it can be useful in treating and preventing the degenerative brain disease as a medicament.

The invention discloses application of k-carrageenan oligosaccharides capable of adjusting activated states of a gitter cell. The k-carrageenan oligosaccharides is used for the gitter cell in a quiescent condition, can promote cell multiplication and improve cell viability, and can further effectively prevent lipopolysaccharide from excessively activating activity of the gitter cell, and reduce damage of peripheral nerve cells because of excessive multiplication of the gitter cell and release of inflammatory factors. The k-carrageenan oligosaccharides can be used for preparing medicine for treatment of nervous system disease and prevention of the nervous system disease which are mediated by the gitter cell. The k-carrageenan oligosaccharides can also be used for improving immunity of organisms by promoting multiplication of immune cells such as the gitter cell. As an agent for treatment of the nervous system disease and an agent for prevention of the nervous system disease, the application of the k-carrageenan oligosaccharides capable of adjusting the activated states of the gitter cell can be added to health food for preventing the nervous system disease and improving the immunity of the organisms and drugs for preventing the nervous system disease and improving the immunity of the organisms, and can also be added to any liquid food and solid food.

The invention discloses an application of minocycline hydrochloride to preparation of a medicine for treating autoimmune uveitis and a treatment method of the autoimmune uveitis. The inventor finds that the minocycline hydrochloride can be used as an early intervention medicine by exploring the treatment effect of minocycline with different administration dosages on the autoimmune uveitis. By inhibiting microglial cell activation of retina tissue, reducing immune cell infiltration and reconstructing a steady state in gastrointestinal tract flora, generation and development of the uveitis are effectively inhibited, a new application is provided for application of the minocycline hydrochloride, and besides, a new strategy and method are provided for early prevention and intervention of the autoimmune uveitis.

The present invention provides a method of treating Alzheimer's Disease by blocking CD-40 receptor-mediated, Aβ-induced microglial cell activation with an agent. Also provided is a method of determining the therapeutic effectiveness of an agent for Alzheimer's Disease by measuring the inhibition of the interaction between the CD40 receptor and its ligand (CD40L) in the presence of the agent. The present invention further provides a method of testing the efficacy of a therapeutic agent by producing a TgAppSW / CD40L deficient mouse and administering to the mouse the therapeutic agent to be tested and determining the efficacy of the drug in suppressing neurodegeneration of Alzheimer's Disease.

The present invention relates to the diagnosis, prevention, delay or reversal of pathological progression associated with abnormal amyloid deposits, such as for example Alzheimer's disease (AD). More specifically, the methods comprise administering specific molecules acting as piezoelectric agonists, such as Yoda1, Jed1, Jed2 or functional analogs thereof, capable of modulating the activation of small glial cells to an anti-inflammatory state and / or interfering with the formation of amyloid-producing peptides and / or increasing their outflow from the central nervous system. These agonists are useful in disease states associated with or at risk of developing brain amyloidosis, such as Alzheimer's disease, Parkinson's disease, stroke, head trauma, brain amyloid angiopathy, spongioencephalopathy, and pruritus. All of the diseases are evidence of abnormal pro-inflammatory microglial cell activation.

Provided are methods for determining the level of microglial activation in the brain of a subject by measuring blood Prostaglandin E2 (PGE2), Prostaglandin F2α, or both, and C-Reactive Protein (CRP) concentrations in a sample obtained from a subject, wherein the ratio of [PGE2] / [CRP], [PGF2α] / [CRP], or both, is indicative of the level of microglial activation in the brain of the subject.

The invention discloses application of phloretin in preparation of antidepressant drugs, and belongs to the technical field of medicines. A mouse depression model is established through chronic unpredictable mild stimulation, the anti-depression effect of the phloretin is evaluated through behavioral detection means such as an open field experiment, a sweet water preference experiment, a tail suspension experiment and a forced swimming experiment, and it is proved through an immunofluorescence experiment and ELISA kit detection that the phloretin can inhibit microglial cell activation; the compound can relieve neuroinflammation and play a neuroprotective role, and can be used for preparing anti-depression drugs.

The invention relates to application of sophocarpidine to inhibition of neuroinflammation and prevention and / or treatment of acute and chronic neurodegenerative diseases caused by the neuroinflammation, in particular to application of sophocarpidine to preparation of medicine for inhibiting neuroinflammation. Pharmacological experiments prove that the sophocarpidine has remarkable inhibition activity of the neuroinflammation and can be used for preparing medicines for preventing and / or treating neuroinflammation and related diseases, so that relatively high clinical application value and development prospect are achieved. The invention discloses application of the sophocarpidine to inhibition of neuroinflammation; furthermore, the pharmacological experiments prove that the sophocarpidine can remarkably inhibit release of LPS induced microglial cell inflammation mediums ROS, IL-6 and PGE2, can remarkably inhibit LPS induced mouse brain microglial cell activation and has the remarkable inhibition activity on the neuroinflammation. Therefore, the compound can be used for preparing the medicines for preventing and / or treating neuroinflammation and related diseases.

The invention provides application of lovastatin to preparing Toll-like receptor 4 signaling pathway activation inhibitors and application of lovastatin to preparing microglial cell downstream inflammatory factor expression inhibitor and microglial cell inflammatory signaling pathway activation inhibitors. In vitro experiments prove that, in microglial cells processed and activated by endotoxins,the level of content of nitric oxide, hydrogen peroxide, reactive oxygen and inflammatory factors can be significantly increased; applied lovastatin can significantly inhibit release of nitric oxide,hydrogen peroxide and reactive oxygen and expression of the inflammatory factors; in BV-2 cells, the nitric oxide inhibiting activity of lovastatin is 11.6-13.8 mu M. In vivo experiments prove that lovastatin can reduce in vivo neuropathic pain of Sprague-Dawley rats and inhibit expression of a microglial cell activation marker of CD11b, thereby signifying the effects of lovastatin on specific regulation of microglial cell activation.

Evidence indicates dysregulation. of the immunoregulatory molecule CD45 occurs in Alzheimer's disease (AD). Transgenic mice overproducing amyloid-β peptide (Aβ) and deficient in CD45 (PSAPP / CD45− / −) recapitulate AD neuropathology. Increased cerebral intracellular and extracellular soluble oligomeric and insoluble Aβ, decreased plasma soluble Aβ increased microglial neurotoxic cytokines TNF-α and IL-1β, and neuronal loss were found in PSAPP / CD45− / − mice compared with CD45-sufficient PSAPP littermates. After CD45 ablation, in vitro and in vivo studies demonstrate a microglial phenotype whereby microglia phagocytose less Aβ but display proinflammatory properties. This microglial activation occurs with elevated Aβ oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP / CD45− / − mice. These data show that deficiency in CD45 activity leads to brain accumulation of neurotoxic Aβ oligomers and validate CD45-mediated microglial clearance of oligomeric Aβ as a novel AD therapeutic target.

The invention discloses an Iba1 and LAG-3 dual-gene co-expression recombinant adenovirus vector and a preparation method and application thereof. The recombinant adenovirus vector comprises a dual-gene expression box for expressing Iba1 and LAG-3, wherein the dual-gene expression box sequentially consists of a CMV promoter, LAG-3 genes, an internal ribosome entry site IRES, Iba1 genes and a terminator. A recombinant adenovirus can be prepared by utilizing the recombinant adenovirus vector; after the prepared recombinant adenovirus is transfected to microglial cells, inflammatory reactions after cerebral hemorrhage can be inhibited, the neurological function of a mouse suffering from cerebral hemorrhage is effectively improved,and the lifetime of the mouse suffering from cerebral hemorrhage is prolonged; and the recombinant adenovirus vector can be used for preparing drugs resisting microglial cell activation and has good development and application prospects in the field of treatment of cerebrovascular diseases.

The invention discloses an application of chrysin in the preparation of medicines for treating cerebral arterial thrombosis. Experimental results of the chrysin show that the chrysin has a relatively good nerve protection effect on focal cerebral ischemia-reperfusion injury, can be used for improving the neurological function loss after the cerebral ischemia-reperfusion injury, reducing the water content in brains, the size of cerebral infarction and the content of malonaldehyde (MDA) and improving the activity of superoxide dismutase (SOD); after focal cerebral ischemia-reperfusion, the chrysin can be used for reducing the relative expression quantity of nuclear factor-kappaB (NF-kappaB) of ischemia-reperfusion brain tissues, inducible nitric oxide synthase (iNOS) and a cyclooxygenase-2 (COX-2) gene; and the chrysin can also be used for reducing the expression of GFAP and Iba1 in the ischemia-reperfusion brain tissues, inhibiting the activation of astrocyte and microglial cells and meanwhile reducing the expression of pro-inflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, IL-12, IL-17A, TNF-alpha and IFN-gamma, thus the excessive inflammatory response of cerebral ischemia tissues is alleviated, and the neuroprotective effect after ischemia is realized.

The invention belongs to the technical field of biological medicines, and particularly relates to application of 18 beta-glycyrrhetinic acid in preparation of a depression-related neuronal protection medicine. The application specifically comprises the following steps: 18 beta-glycyrrhetinic acid can play a role in protecting neurons by inhibiting depression-related microglial cell activation-mediated neuronal apoptosis; meanwhile, the 18beta-glycyrrhetinic acid can activate a nuclear transcription factor Nrf-2 related to depression to start transcription and translation of a brain-derived nerve growth factor so as to play a role in protecting neuronal cells, and the 18beta-glycyrrhetinic acid is obvious in drug effect and free of obvious side effects.

The invention provides applications of a receptor antagonist in treating focal cerebral ischemia injuries, and belongs to the technical field of biological medicine. In rat focal cerebral ischemia models, HAMI 3379 intracerebroventricular administration possesses protection effects on acute injuries of the rat focal cerebral ischemia models; HAMI 3379 intraperitoneal injection administration possesses protection effects on accurate and subacute injuries, and at the same time, inflammatory reaction is reduced, and especially microglial cell activation is inhibited; and HAMI 3379 intraperitoneal injection administration possesses protection effects on cerebral ischemia chronic injuries, and neurological function recovery can be promoted.

The invention discloses a monoclonal antibody derived from 4Abeta1-15. The monoclonal antibody is generated by a hybridoma cell strain with the preservation number of CCTCC C201473. The monoclonal antibody disclosed by the invention can be used for eliminating Abeta deposition without leading to micro-bleeding burden, and meanwhile, fewer microglial cells are activated so as to prevent inflammatory factors and T cells from being further excessively activated, so that the monoclonal antibody can be used for preventing and treating Alzheimer's disease.

The invention provides a Cx3cr1CreER-Ai27 genotype double-transfected mouse and a novel microglial cell activation method. The Cx3cr1CreER-Ai27 genotype double-transfected mouse is obtained by hybridizing a Cx3cr1CreER-Ai27 genotype mouse and an Ai27 gene mouse, an optical fiber is implanted in a target brain region after Tamoxifen is injected into an abdominal cavity, and microglial cells in a region below the optical fiber can be specifically activated by using blue light (450-490nm) for stimulation. The microglial cell activation method can specifically activate the microglial cells and accurately distinguish the microglial cells from other cells, and has important significance in research on development, behaviors, functions and the like of the microglial cells, and the novel microglial cell activation method is simple and convenient to operate, reduces research cost and risks, and has wide application prospects.

The invention discloses an application of a small molecule compound, the small molecule compound is N-(2-(1-(4-chlorphenyl)-5-hydroxy-3-phenyl-1-hydro-pyrazole-4-yl)-2-acetyl)-4-methyl-N-propyl benzamide, the chemical structural formula of the small molecule compound is shown in the specification, and the small molecule compound has a relatively strong inhibition effect on MIF. The small molecule compound has obvious inhibition effect on microglial cell activation and inflammatory factor release, has low cytotoxicity, has good development prospect, is expected to be developed into a novel MIF inhibitor, is expected to be developed into a novel medicine for resisting central system inflammation, and especially is expected to be developed into a novel medicine for treating depression.

The invention discloses a monoclonal antibody derived from 4Abeta1-15. The monoclonal antibody is generated by a hybridoma cell strain with the preservation number of CCTCC C201473. The monoclonal antibody disclosed by the invention can be used for eliminating Abeta deposition without leading to micro-bleeding burden, and meanwhile, fewer microglial cells are activated so as to prevent inflammatory factors and T cells from being further excessively activated, so that the monoclonal antibody can be used for preventing and treating Alzheimer's disease.

The present invention provides brain cells, such as normal brain cells, apolipoprotein E deficient brain cells, or apoE4 containing brain cells, that are treated with a compound which can modulate integrins and / or integrin receptors to produce increased sequestration of and / or accumulation of and / or uptake of Aβ, and / or changes in cathepsin D content and / or lysosomal dysfunction, and / or microglia activation in the brain cells. The present invention also provides methods for producing such cells and methods for using the cells for screening an agent or substance that modulates the sequestration of and / or accumulation of and / or uptake of Aβ, and / or lysosomal dysfunction, and / or changes in cathepsin D content and / or microglia activation in the brain cells. The method further provides a new therapeutic target, antagonism of glutamate receptors, for the treatment of neurodegenerative diseases which are characterized by inter alia, abnormal amyloid uptake and / or accumulation.

Provided are methods for determining the level of microglial activation in the brain of a subject by measuring blood Prostaglandin E2 (PGE2), Prostaglandin F2α, or both, and C-Reactive Protein (CRP) concentrations in a sample obtained from a subject, wherein the ratio of [PGE2] / [CRP], [PGF2α] / [CRP], or both, is indicative of the level of microglial activation in the brain of the subject.

The invention provides a vitamin B6 + probiotic mixture and application thereof in preparation of drugs for relieving stress-related secondary injuries and aseptic inflammations, based on microbiomics and metabonomics studies performed after a rat is subjected to chronic stress treatment in a basic experiment, probiotics and vitamin B6 are applied to a chronic stress rat model, and the stress-related secondary injuries and aseptic inflammations are relieved. Through detection of brain injury related parameters, peripheral stress and inflammation levels and intestinal flora omics and supplement of probiotics and vitamin B6, the inflammation level of hippocampus can be relieved, the microglial cell activation level can be reduced, hippocampus neuron neogenesis can be improved, peripheral blood glucose corticoid and inflammation levels can be reduced, and intestinal flora disorder can be corrected; it is indicated that supplement of probiotics and vitamin B6 has a positive effect on prevention and treatment of stress-related secondary injuries and has a good application prospect in preparation of drugs for relieving stress-related secondary injuries and aseptic inflammations.

The invention relates to an application of chitosan nanogel loaded with oxytocin in preparation of a medicine for early intervention of Alzheimer's disease. The research finds that the chitosan nanogel loaded with oxytocin has a remarkable effect in the aspect of early treatment of the Alzheimer's disease. Cellular level experiment results show that the chitosan nanogel loaded with the oxytocin can inhibit microglial cell activation caused by lipopolysaccharide and reduce expression of inflammatory factors in microglial cells. Animal level experiment results show that the chitosan nanogel loaded with the oxytocin can significantly reduce the expression level of inflammatory factors of hippocampus of an early model mouse with the Alzheimer's disease, significantly reduce beta-amyloid protein deposition and neuron damage, and significantly improve the learning and memory ability of the early model mouse with the Alzheimer's disease. The chitosan nanogel loaded with the oxytocin is simple in preparation process, mild in reaction condition and easy in surface modification.

The invention discloses an application of glycyrrhizic acid or a derivative thereof in preparation of a medicine for treating retinitis. It is found that glycyrrhizic acid or derivatives thereof or pharmaceutically acceptable salts thereof can effectively reduce fundus retina inflammation focuses, inhibit retina microglial cell activation and inflammatory response and reduce and inhibit retina tissue damage and inflammatory cell infiltration, has the potential of being developed into retinitis treatment drugs, and can be applied to treatment of retinitis. Patients can be prevented from being troubled by diseases such as hypertension and hyperosteogeny caused by hormone medicines.

The invention discloses application of lycium barbarum glycopeptide in preparation of a medicine for relieving neuropathic pain, and relates to the field of lycium barbarum glycopeptide research. The invention also discloses an application of the wolfberry glycopeptide in preparation of a medicine for improving spinal microglial cell activation caused by nerve injury. The invention relates to application of wolfberry glycopeptide in preparation of a medicine for improving spinal astrocyte activation caused by nerve injury and application of wolfberry glycopeptide in preparation of a medicine for improving spinal neuron voltage-gated sodium channel Nav1.3 expression caused by nerve injury, in particular to application of wolfberry glycopeptide in preparation of a medicine for improving spinal neuron voltage-gated sodium channel Nav1.3 expression caused by nerve injury.

The invention belongs to the technical field of pharmaceutical researches, and particularly provides application of pectolinarin in preparation of neuroinflammation inhibitors. Cell experiments prove that the pectolinarin can inhibit mRNA expression and protein expression of inflammatory factors TNF-alpha and IL-6 activated and released by LPS-induced microglial cells BV2 and oxidative stress reaction generated by activation of the microglial cells BV2.

The invention discloses application of pregabalin in preparation of a medicine for preventing or treating radiation brain injury, and relates to the technical field of new application of medicines. It is found that pregabalin can inhibit increase of inflammatory factors and microglial cell activation caused by radiation brain injury in a radiation brain injury mouse model, neuron injury and apoptosis induced by inflammation are further improved, and no obvious side effect exists. The pregabalin can be used for developing a novel medicine for preventing or treating radiation brain injury, and has wide medical prospect and economic value.

Compositions and methods of using ILC2 to reduce microglial activation or to reduce blood-brain barrier (BBB) permeability are described. Also described are methods and compositions that use an agent that increases the number of activated ILC2 to reduce microglial activation or BBB permeability.