imm-h004 and Disease-Models--Animal

imm-h004 has been researched along with Disease-Models--Animal* in 4 studies

Other Studies

4 other study(ies) available for imm-h004 and Disease-Models--Animal

ArticleYear
IMM-H004 reduced okadaic acid-induced neurotoxicity by inhibiting Tau pathology in vitro and in vivo.
    Neurotoxicology, 2019, Volume: 75

    This study aimed to explore effects and mechanisms of 004 (IMM-H004), a novel coumarin derivative, in OKA (okadaic acid)-induced AD (Alzheimer's disease)-like model. In vitro, MTT, LDH, and Annexin V/FITC flow cytometry assay were used to test cell survival. In vivo, OKA microinjection was conducted to simulate AD-like neuropathology. Morris water maze and Nissl staining were used to detect spatial memory function and neuronal damage respectively. Western blot and immunohistochemistry were used to study the mechanisms of 004 in Tau pathology. The results showed that 004 reduced cell death and increased survival in PC12 cells, and decreased neuronal injury in the hippocampus in rats. 004 improved learning and memory functions in OKA-treated rats. The mechanistic studies indicated that 004 inhibited phosphorylation of Tau protein by down-regulating the activity of protein kinases CDK5 and GSK3β and increasing PP2A activity. Overall, 004 improved spatial memory impairments and neuron cells injury induced by OKA; on the other hand, 004 inhibited Tau hyperphosphorylation by regulating CDK5, GSK3β and PP2A.

    Topics: Alzheimer Disease; Animals; Apoptosis; Blotting, Western; Coumarins; Disease Models, Animal; Flow Cytometry; Male; Maze Learning; Neuroprotective Agents; Okadaic Acid; PC12 Cells; Rats; Rats, Sprague-Dawley; tau Proteins

2019
IMM-H004, A New Coumarin Derivative, Improved Focal Cerebral Ischemia via Blood-Brain Barrier Protection in Rats.
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2017, Volume: 26, Issue:10

    IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a novel coumarin derivative that showed better effect in improving global cerebral ischemia in rats. However, the effects and mechanisms in focal cerebral ischemia were not clear. Blood-brain barrier (BBB) protection is a vital strategy for the treatment of cerebral ischemia. This study is to investigate whether IMM-H004 improves brain ischemia injury via BBB protection.. Focal brain ischemia model was induced by middle cerebral artery occlusion for 1 hour and reperfusion (MCAO/R) for 24 hours in rats. IMM-H004 (1.5, 3, 6 mg/kg) and edaravone (positive drug, 6 mg/kg) were administered after 5 minutes of occlusion. Neurological score and TTC staining were used to evaluate the effect of IMM-H004. Evans Blue (EB) staining and electron microscopy were used to assess BBB permeability. Western blot, reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect the expression of BBB structure-related proteins.. Compared with the model group, IMM-H004 in the focal brain ischemia model improved neurological function and reduced cerebral infarction size and edema content. IMM-H004 sharply reduced the EB content and alleviated BBB structure. In addition, IMM-H004 increased the level of zonula occludens (ZO-1) and occluding, decreased the level of aquaporin 4 and matrix metalloproteinase 9, either in cortex or in hippocampus. And all of these changed were related to BBB protection.. IMM-H004 improved cerebral ischemia injury via BBB protection. For a potential therapy drug of cerebral ischemia, IMM-H004 merits further study.

    Topics: Animals; Aquaporin 4; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Cerebral Cortex; Coumarins; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Infarction, Middle Cerebral Artery; Male; Matrix Metalloproteinase 9; Neuroprotective Agents; Occludin; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Zonula Occludens-1 Protein

2017
Compound IMM-H004, a novel coumarin derivative, protects against CA1 cell loss and spatial learning impairments resulting from transient global ischemia.
    CNS neuroscience & therapeutics, 2015, Volume: 21, Issue:3

    Compound IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a new synthetic derivative of coumarin, and previous studies showed that it exhibited antioxidant and neuroprotective roles in focal cerebral ischemia. However, we know little about the compound's function in transient global ischemia. This study is to investigate whether compound IMM-H004 can protect against transient global ischemic injury.. Four-vessel occlusion (4VO) rat model was induced for a 20-min occlusion and different times of reperfusion to mimic transient global cerebral ischemia. IMM-H004 (3, 6, 9 mg/kg) or Edaravone (6 mg/kg) was administered after 30 min of reperfusion. Morris water maze tests were used to estimate the ability of spatial learning and memory. Nissl staining, TUNEL assay and Immunoblot for Bax/Bcl-2 and activated caspase-3 were used to detect hippocampal neuron injury. Immunoblot for PSD-95 and synapsin 1, and electron microscopy were used to observe synaptic function.. Compared with vehicle group, IMM-H004 significantly improved the spatial learning performance and exhibited less CA1 neurons loss. The expressions of Bax/Bcl-2 and activated caspase-3 were decreased. IMM-H004 also ameliorated synaptic structure, decreased PSD-95 and increased synapsin 1 expression.. These findings suggested that IMM-H004 exerted neuroprotective role in global ischemia by reducing apoptosis and maintaining the integrity of synaptic structure.

    Topics: Animals; Antipyrine; bcl-2-Associated X Protein; Brain Ischemia; CA1 Region, Hippocampal; Caspase 3; Cell Death; Coumarins; Disease Models, Animal; Disks Large Homolog 4 Protein; Drug Evaluation, Preclinical; Edaravone; Free Radical Scavengers; Intracellular Signaling Peptides and Proteins; Learning Disabilities; Male; Maze Learning; Membrane Proteins; Neurons; Neuroprotective Agents; Nootropic Agents; Random Allocation; Rats, Sprague-Dawley; Spatial Memory; Synapsins

2015
IMM-H004 prevents toxicity induced by delayed treatment of tPA in a rat model of focal cerebral ischemia involving PKA-and PI3K-dependent Akt activation.
    The European journal of neuroscience, 2014, Volume: 39, Issue:12

    Ischemic stroke is currently treated with thrombolytic therapy with a drawback to induce hemorrhagic transformation (HT) if applied beyond its relatively narrow treatment time window. The present study was designed to examine the role of IMM-H004, a derivative of coumarin, in recombinant tissue plasminogen activator (tPA)-induced HT. Rats subjected to 6 h of thromboembolic occlusion or middle cerebral artery occlusion received tPA with or without IMM-H004. Delayed tPA intervention drastically increased the risk of HT and exaggerated the ischemic injury. To assess the effect of IMM-H004 on delayed treatment of tPA-induced toxicity after ischemia and reperfusion, various approaches were used, including a behavior test, TTC-staining, determination of cerebral hemorrhage, laser speckle imaging, Western blot, gelatin zymogram, immunohistochemistry and immunofluorescence staining. Experiments were also conducted in vitro in human brain microvascular endothelial cells (HBMECs) and PC12 cells to explore the mechanism for the role of IMM-H004. Combination therapy of tPA and IMM-H004 prevented the development of HT, and reduced the mortality rate, infarct volume and brain edema. IMM-H004 also exerted a protective role by decreasing matrix metalloproteinases, the co-localization of matrix metalloproteinase-2 with astrocytes and increasing occludin. Experiments in HBMECs and PC12 revealed an elevation in ATP level and a protein kinase A- and PI3K-dependent activation of Akt by IMM-H004 after tPA administration. These results suggest IMM-H004 as a promising adjuvant to alleviate the detrimental side effects of tPA in clinical therapy of ischemic stroke, and contribute to better understand the mechanism for the beneficial role of this novel remedy.

    Topics: Animals; Brain; Brain Ischemia; Cells, Cultured; Cerebral Hemorrhage; Coumarins; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Endothelial Cells; Fibrinolytic Agents; Humans; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; PC12 Cells; Proto-Oncogene Proteins c-akt; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Thromboembolism; Time Factors; Tissue Plasminogen Activator

2014