193 results about "Axon" patented technology

The invention relates to the technical field of biological materials, in particular to a hydrogel scaffold material for spinal cord injury repair as well as a preparation method and application of the hydrogel scaffold material. The hydrogel scaffold material AP39 (AP39-coated LIP) for spinal cord injury repair is prepared by combining the liposome-coated AP39 (AP39-coated LIP) serving as a drug with a GelMA hydrogel scaffold, and a scaffold is provided for injured spinal cords, so that axon regeneration of injured parts is guided, mitochondria of the injured parts is targeted to release H2S, neuronal injury is relieved, and the spinal cord injury repair effect is improved. Therefore, nerve regeneration and functional recovery after spinal cord injury are promoted.

The invention discloses a bone organ chip loaded with a microelectrode array and a use method, and relates to the technical field of organ chips, the bone organ chip is made of a polydimethylsiloxane material, and the bone organ chip comprises a three-layer structure: a top layer, a middle layer and a bottom layer; the middle layer comprises two blood vessel micro-channels, two osteoblast micro-channels and a neuron micro-channel, the channels are separated through columns and micro-columns, and cell interaction in a bone micro-environment is simulated; a microelectrode array is arranged on the top layer and is used for monitoring electrical activity of neurons in real time; the bottom layer is provided with a pneumatic valve which can control opening and closing of the micro-channel. According to the invention, nerve and blood vessel channels are introduced, a nerve-blood vessel-immunoregulation bone microenvironment is constructed, physiological processes such as osteogenesis-blood vessel formation coupling and the like are embodied, intervals of different sizes can enhance intercellular crosstalk and allow blood vessels and neuron axons to selectively pass through, so that the chip can simulate a complex microenvironment of bone tissues, and the microenvironment of the bone tissues can be simulated; and an efficient and accurate in-vitro model is provided for bone disease mechanism research and drug development.

Compositions comprising microalgal extracellular vesicles (MEVs) formulated for intranasal delivery are provided, whereby upon intranasal administration, the MEVs are transported by a specific route, to specific regions in the brain via the olfactory nerve after intranasal administration, and to interconnected brain regions through the lateral olfactory tract (LOT). The MEVs are transported via neuronal axonal transport. The MEVs have the ability to cross synapses including: (i) synapses between olfactory sensory neurons (OSNs) and mitral / tufted neurons; (ii) synapses between mitral / tufted neurons and local neurons in multiple brain regions colonized by the lateral olfactory tract (LOT); and (iii) synapses between neurons in brain regions colonized by the LOT and neurons from the frontal cortex, hippocampus, thalamus, and hypothalamus. The compositions contain extracellular vesicles (MEVs) from microalgae loaded with bioactive cargo for the treatment, detection, diagnosis, or monitoring of diseases, disorders, or conditions of or involving the brain, particularly neuronal delivery of the cargo. The compositions and methods have multiple applications as therapeutic and diagnostic agents for the treatment, diagnosis, and monitoring of diseases, disorders, or conditions of or involving the brain. The compositions can be used in methods and uses for the treatment of cancers involving the brain, and can be used, for example, to deliver therapeutic agents for psychiatric diseases, disorders, conditions, and to deliver therapeutic agents for neurodegenerative diseases, disorders, and conditions.

The invention belongs to the field of medicines, and discloses application of a stress-induced stem cell extract in treatment of cerebral apoplexy. The inventor finds that stem cells are cultured under proper stress conditions through screening, and the separated stem cell extract (also known as Alritoin) can increase the axon length and dendritic length of normal primary neurons and is beneficial to growth and conduction of nerve fibers; in a pdMCAO model, the volume of cerebral infarction in the acute stage of ischemia of a mouse can be remarkably reduced, the neurological function score can be improved, and a relatively good improvement trend is achieved in the aspect of cognition; in the acute stage of cerebral ischemia reperfusion, the pharmaceutical composition has remarkable effects on reducing the cerebral infarction volume of a mouse, reducing relative edema and improving the neurological function, and is relatively long in medication time window; in a cerebral ischemia reperfusion model, the trend of improving local cerebral blood flow is shown. The allitoin is expected to be developed into a promising drug for cerebral apoplexy, especially a drug for treating ischemic cerebral apoplexy.

A system may be configured for treating a patient with epileptic seizures. The system may include a therapy delivery system configured to use a set of electrodes positioned adjacent to a spinal cord or dorsal column nuclei and a stimulation configuration to deliver neuromodulation energy to at least one target neural pathway in or near the spinal cord. The at least one target neural pathway includes the dorsal column nuclei or axons projecting to the dorsal column nuclei. The dorsal column nuclei and the axons are somatotopically organized and project to at least one of a cerebellum, a thalamus or a brainstem, which include somatotopically organized nuclei and project axons to different areas of a cortex. The at least one target neural pathway corresponds to at least one of the different areas of the cortex in which the epileptic seizures were located.

The invention discloses a fusion polypeptide TGNL and application of neural stem cells modified by the fusion polypeptide TGNL in spinal cord injury repair. The fusion polypeptide TGNL is composed of a TAT penetrating domain, a GSTP targeting domain, an NICDi inhibition domain, an MMP-2 activation domain and a flexible Linker connecting the three domains, and the full-length amino acid sequence is as shown in SEQ ID NO. 1. The invention also provides a preparation method of the polypeptide, a neural stem cell (hNSCs-TGNL) for expressing the polypeptide and a construction method of the neural stem cell (hNSCs-TGNL). Experiments show that the fusion polypeptide TGNL can efficiently penetrate nerve cells, specifically target glial scars, is selectively activated by MMP-2, and promotes neural stem cells to differentiate into neurons by inhibiting Notch signals; the hNSCs-TGNL has high survival rate and strong penetrability in an in-vitro glial scar model, and can significantly promote motor function recovery, reduce injury volume, increase axon density and reduce glial scars in a rat spinal cord contusion model. The invention provides a novel candidate drug and a cell treatment strategy for clinical treatment of spinal cord injury, and has remarkable clinical application value.

The invention relates to the technical field of brain science image processing, and discloses a brain tissue neuronal morphology three-dimensional reconstruction and connection group analysis method and system, and the method comprises the steps: carrying out the feature point extraction and matching and optical flow registration of continuous ultrathin section electron microscope images, and obtaining three-dimensional image volume data; carrying out semantic segmentation on cell bodies, dendrites, axons and dendritic spines through a three-dimensional deep convolutional neural network, and driving secondary registration through confidence feedback; detecting synapses and classifying the synapses as excitatory or inhibitory types; executing topology perception skeletonized reconstruction and performing segmentation correction through topology anomaly feedback constraint; and constructing a synaptic connection matrix and executing graph theory analysis.

The invention relates to a nerve repair guide catheter, a preparation method and application, an electrostatic spinning technology is adopted to construct a nanofiber membrane which is directionally and orderly arranged so as to guide nerve axons to directionally grow, and cell energy metabolism is promoted and tissue repair and regeneration are accelerated through metabolism and conversion of degradation products. Therefore, the nerve injury repairing effect better than that of traditional matrix materials without biological activity, such as PCL, is achieved. According to the invention, a novel solution is provided for solving the problem of insufficient biological activity of a traditional nerve conduit material by constructing a degradable high polymer material with biological activity. Therefore, the regeneration efficiency of peripheral nerve injury repair is improved, and the application prospect of the bioactive material in the fields of tissue engineering and regenerative medicine is expanded.

The invention discloses a fruit image classification method based on a wide area network dendritic neuron model, and the method comprises the steps: achieving the multi-scale feature extraction through parallel 1 * 1, 3 * 3 and 5 * 5 convolution and pooling branches, carrying out the fusion convolution, LeCannTanh activation and batch normalization, generating a feature representation through the combination of global average pooling and a lightweight feedforward network, and carrying out the classification of fruit images through the feature representation. And self-adaptive nonlinear classification is realized by means of synaptic-dendritic-somatic cell-axon hierarchical processing of dynamic dendritic neurons. Experimental results show that the method has the advantages of high precision, high robustness and low time delay in scenes with complex backgrounds, large intra-class differences and small samples, and is suitable for industrial applications such as intelligent sorting and automatic quality inspection.

Methods are disclosed for increasing retinal ganglion cell (RGC) survival and / or RGC axon regeneration and / or optic nerve survival and / or optic never regeneration in a subject in need thereof. These methods include locally administering to an eye of the subject a therapeutically effective amount of (a) isolated nanovesicles derived from an extracellular matrix and (b) a statin or a pharmaceutically acceptable salt thereof. Combination therapy is also disclosed for use in increasing RGC survival and / or RGC axon regeneration and / or or optic nerve survival and / or optic nerve regeneration in a subject. Disclosed is therapeutically effective amount of (a) isolated nanovesicles derived from an extracellular matrix and (b) a statin or a pharmaceutically acceptable salt thereof, for use in increasing RGC survival, RGC axon regeneration and / or optic nerve survival and / or optic never regeneration in a subject in need thereof in a subject, wherein the isolated nanovesicles and the statin are formulated for ophthalmic administration.

The invention discloses an exosome and optic nerve injury prognosis evaluation method and system, and relates to the field of data processing and artificial intelligence, and the method comprises the steps: carrying out the collection and prognosis grade labeling of optic nerve MRI data; carrying out adaptive processing on the three-dimensional MRI voxel data by adopting anisotropic Gaussian interpolation so as to retain a micron-sized structure of an optic nerve fiber layer; constructing a double-branch gating classification network, extracting axonal injury and fusion prognosis related features through independent branches, and training by combining a dynamic focus loss function with confidence loss; and finally, the prognosis probability distribution of the patient is output through the model. According to the method, multi-modal information can be effectively fused, tiny damage feature characterization is enhanced, and the accuracy and interpretability of prognosis evaluation are improved.

The invention provides application of tea catechin in preparation of a medicine for preventing and treating bortezomib-induced peripheral neuropathy. A plurality of in-vitro model results show that tea catechin can be used as a copper death inhibitor, remarkably improves related indexes of bortezomib-induced peripheral neuropathy, improves survival rates of Schwanton cells and SH-SY5Y, improves mitochondrial functions and cell cycle abnormalities of the Schwanton cells, reduces intracellular copper ion, cuprous ion and ATP levels, and can be used for preparing the copper death inhibitor for the peripheral neuropathy of the Bortezomib-induced peripheral neuropathy of the Bortezomib-induced peripheral neuropathy. Meanwhile, the death of Schwann cells and SH-SY5Y induced by the copper death inducer is reduced. In-vivo experiments show that the tea catechin plays a role in protecting functional damage of the bortezomib, and the tea catechin remarkably improves mechanical hyperalgesia, gait abnormality and pathological changes of myelin sheath and axon of mice caused by peripheral neuropathy induced by the bortezomib. The tea catechin can be used as a medicine for peripheral neuropathy induced by bortezomib, and has high clinical application value and development prospect.

The invention relates to the technical field of curative effect prediction, in particular to a curative effect prediction method and system for treating spinal cord injury by stem cells, and the method comprises the following steps: obtaining a multi-parameter metabolism sequence and constructing an activation rhythm map, recognizing a neural restoration synchronization section, extracting a metabolism dominant path and evaluating electrical signal response, generating a para-position map layer and predicting a curative effect trend. According to the method, through introduction of cross-time-sequence metabolism and trend synchronous identification of electrophysiological indexes, dynamic mapping of stem cell activation rhythms is realized, neural axon morphological changes and cerebrospinal fluid metabolism parameters are linked, and distribution positions of key response points in a treatment cycle are determined; the method comprises the following steps: establishing a causal path based on a sequence of metabolic mutation and neural restoration events, extracting an evolution stage dominated by a metabolic driving effect, marking a matching trend of a curative effect response and an intervention path on a time axis, identifying the number and positions of trend convergence, withdrawal and interruption areas, and realizing collaborative prediction of a restoration progress and a curative effect trend.

This invention relates to diselenylene-bridged mesoporous silica nanoparticles loaded with baicalin and their applications. The invention constructs a ROS-responsive, microglia-inspired Ba@Se-MSN&BV2 nanoplatform targeting the secondary phase of spinal cord injury. The BV2 cell membrane-mediated enrichment at the injury site, combined with the diselenylene-triggered, on-demand release of baicalin, enables targeted intervention in a highly oxidative and pro-inflammatory microenvironment. In vitro and in vivo studies show that Ba@Se-MSN&BV2 can alleviate oxidative stress and mitochondrial dysfunction, inhibit apoptosis, promote axonal and neuronal survival, and improve motor circuit function. This invention provides a new therapeutic target and research direction for neuroinflammatory injuries driven by redox homeostasis disruption, with significant clinical application prospects and social value.

Disclosed herein are anti-RGMa antibodies and methods of using these antibodies to treat spinal cord injury, including promoting axonal regeneration, functional recovery, or both and to treat pain, including neuropathic pain arising from spinal cord injury.

The invention belongs to the technical field of biological medicine, and particularly relates to a single-domain antibody VHH-L1 targeting LINGO-1 protein, and the amino acid sequence of the single-domain antibody VHH-L1 is shown as SEQ ID NO: 1. The single-domain antibody has nanomole-level high affinity and excellent specificity, can effectively block the interaction between LINGO-1 and ligands thereof, and remarkably promotes differentiation and myelination of oligodendroglia cells. The invention further provides a neural stem cell subjected to genetic engineering modification, and the neural stem cell can stably and continuously secrete the single-domain antibody VHH-L1. In a spinal cord injury animal model, the engineered stem cell shows an excellent treatment effect, can significantly promote motor function recovery, axon regeneration and myelin sheath repair, and effectively inhibits glial scar formation. The double advantages of cell therapy and long-acting protein delivery are fused, and a brand new efficient treatment strategy is provided for demyelination diseases such as multiple sclerosis and spinal cord injury.

The present invention discloses a microfluidic bio-interconnected neural network chip and a preparation method thereof. The chip consists of a microelectrode array, a microfluidic structure, and a cell culture ring structure. The microelectrode array can detect and stimulate the activity of neurons; the microfluidic structure limits the growth direction of axons between cell culture partitions by setting cell culture partitions, microfluidic channel dimensions, microfluidic channel shapes, and fillet distribution, thereby achieving controllable low-power transmission of neuronal electrical information; the cell culture ring structure provides nutrients for cells in the cell culture chamber. The present invention provides a method for manufacturing a microfluidic bio-interconnected neural network chip, using fully exposed positive photoresist as a sacrificial layer for microfluidic structure peeling, thereby solving the problem of difficult demolding of thin-film microfluidic structures. The chip can be used to explore the response characteristics of neuronal networks to external stimuli, study the internal information transmission mode of neuronal networks, and other fields.

The invention relates to a degradable nerve repair membrane and a preparation method thereof, and belongs to the technical field of nerve repair membranes, the degradable nerve repair membrane comprises a biological composite structure inner layer, a support outer layer and a bonding layer, and the biological composite structure inner layer and the support outer layer are bonded through the bonding layer. According to the invention, polypyrrole with excellent electrochemical activity, environmental stability, controllable conductivity and poor mechanical properties and collagen nanofibers with high biocompatibility and capable of forming a nano-scale fiber network are adopted to form a conductive-biological composite structure as an inner layer through electrostatic spinning, and the PLGA porous membrane is prepared through 3D printing. A PLGA porous membrane with parallel axial microchannels on the surface is used as an outer layer, so that the membrane body structure can effectively guide directional growth of axons while ensuring conductivity, accurate preparation can be realized according to needs, the degradation period is matched with the nerve regeneration rate, and the degradation time can be regulated and controlled through the proportion of a copolymer; the repairing effect is prevented from being influenced by too fast or too slow degradation.

The present invention provides compositions and methods for modulation of neuronal networks in the CNS and / or PNS. In certain embodiments, the invention includes modulation of existing networks or restoring one or more damaged or lost axonal connections. In one embodiment, the invention comprises a tissue-engineered composition comprising an elongated tubular construct having at least one neuron and axon extending through the core of the construct.

A neuromorphic computing method includes comparing a maximum number of axons in which a size of a crossbar of a hardware-based node is considered with a number of input neurons, when the number of input neurons exceeds the maximum number of axons, grouping some of input neurons in consideration of the maximum number of axons, obtaining a spike output for a generated group, and inputting the spike output, together with remaining input neurons that are not included in the group, to any one node, and then processing the spike output.

Methods of treating epilepsy are provided. Accordingly, there is provided a method of treating epilepsy in a subject in need thereof, the method comprising: (a) administering into a thalamus nucleus of the subject a therapeutically effective amount of a polynucleotide encoding a bistable type II opsin attached to a heterologous ER export signal and / or membrane trafficking signal which enables trafficking of said bistable type II opsin to axonal presynaptic terminals; and (b) exposing a neural region of said subject to light in a wavelength that activates said bistable type II opsin, wherein said neural region comprises a cell body and / or an axon of said thalamus nucleus.

The invention belongs to the technical field of medicines, and relates to injectable piezoelectric hydrogel for a spinal cord injury part as well as a preparation method and application of the injectable piezoelectric hydrogel. According to the hydrogel, methacrylated gelatin is used as a carrier, and a piezoelectric material MOF (at) PDA (at) M0, namely MP (at) M, of an enveloping porous structure is loaded in the hydrogel. The hydrogel can achieve dual functions under the ultrasonic action: (1) MP (at) M has piezoelectricity, ultrasonic mechanical energy is converted into electrical stimulation, calcium ion inward flow of astrocytes is triggered, mitochondria is promoted to be transferred from the astrocytes to neurons, and the mitochondrial function of the neurons is recovered; (2) the CD73 enzyme carried by the microglial cell membrane coated on the surface of the MP (at) M can degrade pro-inflammatory ATP (adenosine triphosphate) at the damaged part to generate adenosine, so that astrocytes are promoted to release lactic acid, and rapid energy support is provided for neurons. Mitochondrial transfer and energy supply are synchronously promoted through ultrasonic stimulation, neuronal plasticity is remodeled, spinal cord axon regeneration is promoted, and a new strategy is provided for spinal cord injury treatment.

The application discloses application of an inhibitor targeting NLRP3 gene in promoting axon regeneration after sciatic nerve injury. It is found for the first time that NLRP3 expression in DRG is significantly up-regulated after sciatic nerve injury. Further, by interfering with the expression of NLRP3 through siRNA targeting NLRP3, the protein level of NLRP3 can be significantly inhibited, and the increase of the number of DRG neuron axons, the total length of axons and the longest axon length can be obviously promoted. The in-vitro and in-vivo experimental results show that NLRP3 is a negative regulation factor of axon regeneration after sciatic nerve injury, and targeted inhibition of NLRP3 expression can effectively promote axon regeneration. Based on this, the application provides an siRNA sequence targeting NLRP3 and application of the siRNA sequence in preparation of a drug for promoting axon regeneration after sciatic nerve injury. The application provides a new molecular target and intervention strategy for peripheral nerve injury repair, and has important theoretical research value and clinical application prospect.

The invention relates to the technical field of medical apparatus and instruments, and discloses a nerve repair fixing cannula, a flexible connection sheet can be bent into a tubular shape, so that two ends of the flexible connection sheet respectively wrap the peripheries of two nerve broken ends, the inner side of the flexible connection sheet is provided with a growth space, a tubular structure for nerve bridging is established, nerve axons grow directionally, and the two nerve broken ends are kept aligned; the multiple microneedles are arranged at the two ends of the flexible connecting piece at intervals, the connecting tension of the nerve bundle layer and the flexible connecting piece is dispersed, and the pain feeling of a patient is relieved; a needle head of the microneedle is used for being inserted into an adventitia so as to fix the bent flexible connecting piece to the nerve broken end, a needle rod penetrates through the flexible connecting piece, and the needle rod and the outer tangent plane of the bent flexible connecting piece at the needle threading position are obliquely arranged at a first preset angle, so that the mechanical stability of the nerve repair fixing sleeve installed on the nerve broken end is improved; the nerve broken end can be quickly and conveniently fixed, meanwhile, the damage to nerve tracts is reduced, and the situation that the nerve function recovery is affected by scars is avoided.

The invention belongs to the technical field of biological medicines, and discloses application of dasatinib in preparation of a medicine for promoting retina ganglion cell axon regeneration and dendritic repair. The research of the invention finds that dasatinib has the effect of promoting RGC axon regeneration and dendritic repair after optic nerve injury. When dasatinib is adopted for treatment, repair and regeneration of retinal ganglion cell axons and dendrites after optic nerve injury can be promoted, and the purpose of treating traumatic optic nerve injury is achieved.

A novel method of treatment for treating a neurological disease or condition. It involves a compound of Formula (I) or a pharmaceutically or veterinarily acceptable salt thereof, or any stereoisomer or mixture of stereoisomers of a compound of Formula (I) or any pharmaceutically or veterinarily acceptable salt thereof, for use in the treatment or prevention of a neurological disease or condition that results in the destruction or degeneration of neurons, axons, or myelin, wherein R1, R2, and R3 are as defined herein, wherein the treatment comprises: a) a first period of 1 to 7 days, wherein the compound is administered one or more times to a subject in need thereof, and b) a second period of equal to or longer than 13 days, wherein the compound is not administered, wherein the second period occurs after the first period and before the next administration of the compound.

This invention provides a pH-responsive immunomodulatory microneedle patch, its preparation method, and its application, belonging to the field of biomedical materials technology. This invention incorporates Zif-8 nanoparticles loaded with ChABC into GelMA hydrogel to prepare a pH-responsive immunomodulatory microneedle patch (Z@C-MN). As the patch gradually degrades, the system can continuously release Zn in a pH-responsive manner. 2+ Z@C-MN, along with ChABC, promotes in situ repair of cerebral fibrosis (SCI) after injury. Z@C-MN induces macrophage polarization towards a pro-regenerative phenotype, thereby downregulating the inflammatory response, increasing neurite length, and promoting the differentiation of neural stem cells into neurons. In vivo, Z@C-MN reduced the inflammatory microenvironment after injury and promoted angiogenesis in a rat SCI model. Furthermore, it activated axonal regeneration by inhibiting scar tissue formation and regulating CD4+. + T cell transformation supports neurogenesis.

The invention provides application of miR-21 in preparation of a reagent for promoting BMSCs (bone marrow mesenchymal stem cells) differentiation and a medicine for repairing peripheral nerve injury, and belongs to the technical field of biomedicine.The research finds that overexpression of miR-21 in BMSCs can promote BMSCs to be differentiated into SCs-like cells, and miR-21 can improve the efficiency of BMSCs in vivo to be differentiated into the SCs-like cells. In addition, the invention also finds that the BMSCs overexpressing miR-21 can significantly promote PNI posterior process regeneration and myelin sheath formation, thereby improving sciatic nerve motor function recovery and target muscle atrophy; the compound can be applied to preparation of drugs for repairing peripheral nerve injury.

In nerve diseases, cell dysfunction due to amyloid aggregate accumulation in nerve cells has attracted attention, but dysfunction of nerve axons responsible for neurotransmission is also considered to be one of the causes. However, no therapeutic agent that focuses on the repair and maintenance of nerve axons has been found. An object of the present invention is to provide a therapeutic agent that activates oligodendrocytes having a function of preserving nerve axons.SOLUTION: Transcriptome analysis with a psychotropic drug is carried out using an oligodendrocyte marker as an indicator, and it is found that the combined use of DPZ and NFN characteristically increases the expression of a transcriptional factor OLIG1 inducing the differentiation-maturation of the oligodendrocyte. Moreover, the drug concentration at this time was much lower than the expected clinical dose. The combined use of NFN and DPZ was observed to improve spatial memory in the mouse Y-maze test. The combination of NFN and DPZ can provide a novel treatment for cognitive and memory functions associated with neurological disorders.SELECTED DRAWING: None

The invention relates to a tracer compound for whole-cell labelling, comprising: a non-streptavidin- binding biotin analogue, at least one connecting moiety comprising a functional group configured for a click-chemistry reaction, and at least one cross-linkable moiety, preferably wherein the cross-linkable moiety is a (para)formaldehyde cross-linkable group, and the non-streptavidin-binding biotin analogue enables the tracer compound to diffuse within a biological cell with essentially the same properties as biocytin and / or neurobiotin, preferably enabling the detection of cellular protrusions, such as dendrites, dendritic spines and axons. The invention further relates to methods for constructing such tracer compound and for labelling a cell therewith. The invention further relates to kits for carrying out the method according to the invention.