imm-h004 and Learning-Disabilities

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