To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups： the control surgery group with eestrogen administ...To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups： the control surgery group with eestrogen administration （SE）, the control surgery group with normal saline administration （SN）, the middle cerebral artery occlusion （MCAO） group with oestrogen administration （ME） and the MCAO group with normal saline administration （MN）. The MCAO rats were occluded for 90 rain by an intraluminal filament and then recirculated. After 1, 3, 12, 24 and 28 h of MCAO, the rats of the four groups were killed to investigate the infarct volume, apoptosis and neurogenesis. The cerebral infarct volume in the ME group was significantly smaller than that of the MN group （P 〈 0.05）. No significant cell loss was seen in the dentate gyms. Cerebral ischemia led to increased neurogenosis, which is independent of cell death in the ipsilateral dentate gyrus（P 〈 0.05）. BrdU-pesitive cells in the ipsilateral dentate gyms of the ME group were significantly increased when compared with those of the MN group（P 〈 0.05）. In the SE group, BrdU-positive cells in both the ipsilateral and contralateral dentate gyms, were increased when compared with those of the SN group （ P 〈 0.05 ）. We concluded that ocstregen plays an important role in neurogenesis, which is independent of ischemia-induced by MCAO in the hippocampal dentate gyms of rats.展开更多
Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. H...Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure （HF） after myocardial infarction （MI） and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning （IPC） and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia-- known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning （RIPC） has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation （spinal and vagal）, and electroacupuncture （EA）. We discovered and, with others, have elucidated mechanistic aspects of a non- ischemic phenomenon we termed remote preconditioning of trauma （RPCT）. RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline （EA-like treatment） and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus （when applied at reperfusion）. Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective ＂conditioning＂ phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-KB, Stat3/5, protein kinase C, bradykinin, and the mitoKA^P channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.展开更多
文摘To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups： the control surgery group with eestrogen administration （SE）, the control surgery group with normal saline administration （SN）, the middle cerebral artery occlusion （MCAO） group with oestrogen administration （ME） and the MCAO group with normal saline administration （MN）. The MCAO rats were occluded for 90 rain by an intraluminal filament and then recirculated. After 1, 3, 12, 24 and 28 h of MCAO, the rats of the four groups were killed to investigate the infarct volume, apoptosis and neurogenesis. The cerebral infarct volume in the ME group was significantly smaller than that of the MN group （P 〈 0.05）. No significant cell loss was seen in the dentate gyms. Cerebral ischemia led to increased neurogenosis, which is independent of cell death in the ipsilateral dentate gyrus（P 〈 0.05）. BrdU-pesitive cells in the ipsilateral dentate gyms of the ME group were significantly increased when compared with those of the MN group（P 〈 0.05）. In the SE group, BrdU-positive cells in both the ipsilateral and contralateral dentate gyms, were increased when compared with those of the SN group （ P 〈 0.05 ）. We concluded that ocstregen plays an important role in neurogenesis, which is independent of ischemia-induced by MCAO in the hippocampal dentate gyms of rats.
基金supported by grants from the National Institutes of Health (NIHR01 HL091478) for W.Keith Jonesthe National Natural Science Foundation of China (81470425) for Xiaoping Ren
文摘Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure （HF） after myocardial infarction （MI） and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning （IPC） and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia-- known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning （RIPC） has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation （spinal and vagal）, and electroacupuncture （EA）. We discovered and, with others, have elucidated mechanistic aspects of a non- ischemic phenomenon we termed remote preconditioning of trauma （RPCT）. RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline （EA-like treatment） and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus （when applied at reperfusion）. Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective ＂conditioning＂ phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-KB, Stat3/5, protein kinase C, bradykinin, and the mitoKA^P channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.
