Open AccessCompound IMM ‐H004, a Novel Coumarin Derivative, Protects against CA 1 Cell Loss and Spatial Learning Impairments Resulting from Transient Global Ischemia
Author(s) -
Zuo Wei,
Zhang Wei,
Han Ning,
Chen NaiHong
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12364
Subject(s) - neuroprotection , ischemia , synapsin i , morris water navigation task , tunel assay , pharmacology , hippocampal formation , hippocampus , chemistry , apoptosis , medicine , neuroscience , biochemistry , biology , vesicle , membrane , synaptic vesicle
Summary Aims 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. Methods Four‐vessel occlusion (4 VO ) 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. Results Compared with vehicle group, IMM ‐H004 significantly improved the spatial learning performance and exhibited less CA 1 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. Conclusion These findings suggested that IMM ‐H004 exerted neuroprotective role in global ischemia by reducing apoptosis and maintaining the integrity of synaptic structure.