Aerobic Exercise Alleviates Ischemia-Induced Memory Impairment by Enhancing Cell Proliferation and Suppressing Neuronal Apoptosis in Hippocampus / 대한배뇨장애요실금학회지

PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is a possible consequence of several neurological disorders. NLUTD may produce debilitating symptoms and serious complications, such as chronic renal failure, and recurrent urinary tract infections. Many animal studies of NLUTD symptoms have focused on animal models of cerebral ischemia. In the present study, we investigated the effects of treadmill exercise on memory function and its relation to cell proliferation and apoptosis in the hippocampus, following transient global ischemia in gerbils. METHODS: To induce transient global ischemia in gerbil, both common carotid arteries were occluded for 5 minutes. Gerbils in the exercise groups were forced to run on a treadmill exercise for 30 minutes once a day for 2 weeks. Step-down avoidance task and Y maze task were performed. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-staining, immunohistochemistry for 5-bromo-2'-deoxyridine, doublecortin, caspase-3, and Western blot for brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cytochrome c, caspase-3 were conducted. RESULTS: Ischemia caused memory impairment with an increase of cell proliferation, BDNF expression, and apoptosis in the hippocampus. Treadmill exercise improved memory function with further increase of cell proliferation and BDNF expression and a decrease of apoptosis. CONCLUSIONS: The animal model that we have developed and our assessment of the relation between exercise and brain function can be useful tools for future investigations of NLUTD symptoms associated with stroke, particularly ischemic stroke. The present study suggests that treadmill exercise promoted the recovery of brain function after cerebral ischemia.

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway / 대한배뇨장애요실금학회지

PURPOSE: Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils. METHODS: Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c. RESULTS: Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils. CONCLUSIONS: Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.