Perinatal hypoxia-ischemia (HI) remains a critical issue. Cell transplantation therapy could be a potent treatment for many neurodegenerative diseases, but limited works on this kind of therapy have been reported for perinatal HI. In this study, the therapeutic effect of transplantation with neural stem/ progenitor cells (NSPCs) and chondrotinase ABC (ChABC) in a neonatal HI rat model is evaluated. Histological studies showed that the unaffected area of the brain in animals treated with NSPCs together with ChABC was significantly larger than that in the animals treated with vehicle or NSPCs alone. The wet weight of the brain that received the combined treatment was also significantly higher than those of the vehicle and their individual treatments. These results indicate that intracerebroventricular injection of NSPCs with ChABC reduces brain injury in a rat neonatal HI model.
J. Neurochem. (2008) 104, 1565–1576.
Abstract
Chondroitin sulfate (CS) is a major microenvironmental molecule in the CNS, and there have been few reports about its neuroprotective activity. As neuronal cell death by excitotoxicity is a crucial phase in many neuronal diseases, we examined the effect of various CS preparations on neuronal cell death induced by the excitotoxicity of glutamate analogs. CS preparations were added to cultured neurons before and after the administration of glutamate analogs. Then, the extents of both neuronal cell death and survival were estimated. Pre‐administration of a highly sulfated CS preparation, CS‐E, significantly reduced neuronal cell death induced by not only NMDA but also (S)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid or kainate. Neither CS preparations other than CS‐E nor other highly sulfated polysaccharides such as heparin and dextran sulfate exerted any neuroprotective effects. NMDA‐induced current in neurons was not changed by pre‐administration of CS‐E, but the pattern of protein‐tyrosine phosphorylation was changed. In addition, the elevation of caspase 3 activity was significantly suppressed in CS‐E‐treated neurons. These results indicate that CS‐E prevents neuronal cell death mediated by various glutamate receptors, and suggest that phosphorylation‐related intracellular signals and the suppression of caspase 3 activation are implicated in neuroprotection by CS‐E.
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