Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Transient focal cerebral ischemia is the most common type of stroke caused by occlusion of a cerebral artery. It causes both acute and chronic dysfunctions in brain, lowers the quality of life in patients for a long period of lifetime. Neurons in the ischemic core including cerebral cortex and some parts of striatum are immediately damaged after ischemia-reperfusion, sometimes followed by the delayed neuronal death in the areas distant from ischemic core. Hippocampus is a vulnerable region known to show the delayed neuronal death after transient cerebral ischemia, leading cognitive and other dysfunctions in chronic stage. In this symposium, I introduce a possible rat model of post-ischemic depression associated with the neurodegeneration in hippocampal dentate gyrus (DG), which is sensitive to antidepressant.
In the rat model of cerebral ischemia operated with transient right middle cerebral artery occlusion (MCAO, 90min), cognitive functions assessed by Y-maze and novel object recognition tests were impaired. Moreover, significant aggravation of anhedonia assessed by sucrose preference test was observed after 20 weeks of MCAO. As many previous studies reported, neuronal death of the ipsilateral pyramidal neurons in the hippocampal CA1 area started after a few days of reperfusion, reached to the maximal loss of neurons within one week. Further immunohistochemical analysis also showed apoptotic neuronal death of the granular cells (GC) in ipsilateral DG started from two weeks after MCAO, lead to the significant loss of GC at 20 weeks after MCAO. Proliferation and differentiation of the neural stem cells both in ipsi- and contralateral subgranular zone (SGZ) of DG were increased transiently after reperfusion, however, were almost ceased after 6 weeks of MCAO. Chronic administration of an antidepressant imipramine or fluvoxamine started after one week of reperfusion prevented MCAO rats both from aggravation of anhedonia and from neuronal loss of GC in ipsilateral DG with increasing the survival signal characterized by Bcl-2, and partially recovered the neurogenesis in SGZ.
Pathogenesis of post-stroke depression (PSD) is considered to be multifactorial with neurodegenerative, psychogenic, and genetic mechanisms. This rat MCAO-based ischemia model could explain PSD by hippocampal neurodegeneration treatable with antidepressant.
