ABSTRACT
The present study evaluated for the first time the dose-effectiveness, therapeutic time-window and long-term efficacy of the neuroprotection of catalpol by behavioral and histological measures in gerbils subjected to transient global cerebral ischemia. Catalpol (1 mg/kg ip) used immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h significantly rescued neurons in the hippocampal CA1 subfield and reduced cognitive impairment. The neuroprotective efficacy of catalpol became more evident at the doses of 5 and 10 mg/kg. Of great importance were the findings that the neuroprotective efficacy of catalpol still could be seen even when the treatment was delayed 3 h and when the observational period was lasted out 35 days after ischemia. It was reasonable to draw the conclusion that catalpol was truly neuroprotective rather than simply delayed the onset of neuronal damage. These results suggested that catalpol might be of therapeutic value for global cerebral ischemia.
Subject(s)
Ischemic Attack, Transient/drug therapy , Neuroprotective Agents/pharmacology , Quaternary Ammonium Compounds/pharmacology , Animals , Apoptosis/drug effects , Dose-Response Relationship, Drug , Female , Gerbillinae , Hippocampus/pathology , Ischemic Attack, Transient/pathology , Male , Maze Learning , Neuroprotective Agents/chemistry , Quaternary Ammonium Compounds/chemistryABSTRACT
The neuroprotection of catalpol and its mechanism was evaluated in cerebral ischemic model in gerbils. Three groups were designed as sham-operated, ischemia-treated, respectively, with catalpol and saline. Catalpol was injected intraperitoneally immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h with the dose of 5.0 mg/kg. The neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in Y-maze and the survival neurons in CA1 subfield were counted under a microscope after behavioral testing. In addition, apoptosis induced by ischemia was also examined by using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling method. It was shown that catalpol significantly attenuated apoptosis, rescued hippocampal CA1 neurons and reduced cognitive impairment. In order to make clear the mechanism of catalpol's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase together with the content of lipid peroxide in cortex and hippocampus were assayed. The results proved that catalpol significantly reduced the content of lipid peroxide, increased the activity of glutathione peroxidase and decreased the activity of nitric oxide synthase. All these suggested that catalpol was a potential neuroprotective agent and its neuroprotective effects were achieved at least partly by promoting endogenous antioxidant enzymatic activities and reducing the formation of nitric oxide.
