Targeted temperature management(TTM) shows the most promising neuroprotective therapy against hypoxic/ischemic encephalopathy(HIE).In addition, TTM is also useful for treatment of elevated intracranial pressure(ICP).H...Targeted temperature management(TTM) shows the most promising neuroprotective therapy against hypoxic/ischemic encephalopathy(HIE).In addition, TTM is also useful for treatment of elevated intracranial pressure(ICP).HIE and elevated ICP are common catastrophic conditions in patients admitted in Neurologic intensive care unit(ICU).The most common cause of HIE is cardiac arrest.Randomized control trials demonstrate clinical benefits of TTM in patients with post-cardiac arrest.Although clinical benefit of ICP control by TTM in some specific critical condition, for an example in traumatic brain injury, is still controversial, efficacy of ICP control by TTM is confirmed by both in vivo and in vitro studies.Several methods of TTM have been reported in the literature.TTM can apply to various clinical conditions associated with hypoxic/ischemic brain injury and elevated ICP in Neurologic ICU.展开更多
Retinal ischemia causes several vision-threatening diseases, including diabetic retinopathy, retinal artery occlusion, and retinal vein occlusion. Intracellular adenosine triphosphate（ATP） depletion and subsequent i...Retinal ischemia causes several vision-threatening diseases, including diabetic retinopathy, retinal artery occlusion, and retinal vein occlusion. Intracellular adenosine triphosphate（ATP） depletion and subsequent induced endoplasmic reticulum（ER） stress are proposed to be the underlying mechanisms of ischemic retinal cell death. Recently, we found that a naphthalene derivative can inhibit ATPase activity of valosin-containing protein, universally expressed within various types of cells, including retinal neural cells, with strong cytoprotective activity. Based on the chemical structure, we developed novel valosin-containing protein modulators, Kyoto University Substances（KUSs）, that not only inhibit intracellular ATP depletion, but also ameliorate ER stress. Suppressing ER stress by KUSs is associated with neural cell survival in animal models of several neurodegenerative diseases, such as glaucoma and retinal degeneration. Given that a major pathology of ischemic retinal diseases, other than intracellular ATP depletion, is ER stress-induced cell death, KUSs may provide a novel strategy for cell protection in ischemic conditions. Hence, we investigated the efficacy of KUS121 in a rat model of retinal ischemic injury. Intravitreal injections of KUS121, which is clinically preferable route of drug administration in retinal diseases, significantly suppressed inner retinal thinning and retinal cell death, and maintained visual functions. Valosin-containing protein modulation by KUS is a promising novel therapeutic strategy for ischemic retinal diseases.展开更多
Sixty elderly patients, viro cluffered from acute stroke and were admitted within a 1-year period to the Department of Geriatrics in the First Affiliated Hospital of School of Medicine, Zhejiang University, China, und...Sixty elderly patients, viro cluffered from acute stroke and were admitted within a 1-year period to the Department of Geriatrics in the First Affiliated Hospital of School of Medicine, Zhejiang University, China, underwent early rehabilitation in combination with neuroprotective drug therapy. Limb movement, cognitive functions and daily life self-care ability in elderly patients upon admission and discharge were assessed using the Hunt-Hess scale, functional independence measures and mini-mental state examination. The mean duration of hospital stay among the 60 patients was 35 days. Upon discharge, 42 （75%） of the patients exhibited cognitive impairment to varying degrees, and 25 （45%） of the 56 stroke patients who underwent rehabilitation evaluation attained independence in daily living activities, 11 （20%） required intermittent supervision, and 20 （36%） required 24-hour constant supervision during performance of these activities. Results demonstrated that early rehabilitation treatment in combination with neuroprotective therapy for acute stroke was effective.展开更多
基金the National Research University Project of Thailand from Office of Higher Education Commission and Center of Excellence in Integrated Sciences for Holistic Stroke Research from Thammasat University
文摘Targeted temperature management(TTM) shows the most promising neuroprotective therapy against hypoxic/ischemic encephalopathy(HIE).In addition, TTM is also useful for treatment of elevated intracranial pressure(ICP).HIE and elevated ICP are common catastrophic conditions in patients admitted in Neurologic intensive care unit(ICU).The most common cause of HIE is cardiac arrest.Randomized control trials demonstrate clinical benefits of TTM in patients with post-cardiac arrest.Although clinical benefit of ICP control by TTM in some specific critical condition, for an example in traumatic brain injury, is still controversial, efficacy of ICP control by TTM is confirmed by both in vivo and in vitro studies.Several methods of TTM have been reported in the literature.TTM can apply to various clinical conditions associated with hypoxic/ischemic brain injury and elevated ICP in Neurologic ICU.
基金supported in part by research grants from the Astellas Foundation for Research on Metabolic Disorders,the Japan Foundation for Applied Enzymology,the Uehara Memorial Foundation,Mochida Memorial Foundation for Medical and Pharmaceutical Research,YOKOYAMA Foundation for Clinical Pharmacology(YRY1308)Japan Intractable Diseases Research Foundation,Japan Research Foundation for Clinical Pharmacology,ONO Medical Research Foundation,Takeda Science Foundation,Japan National Society for the Prevention of Blindness,a Grant-in-Aid for Young Scientists(24791850,to IHO+2 种基金15K20255,to HM)the Ministry of Education,Culture,Sports,Science,and Technology of Japan(to IHO)the Ministry of Health,Labour and Welfare of Japan(to IHO)
文摘Retinal ischemia causes several vision-threatening diseases, including diabetic retinopathy, retinal artery occlusion, and retinal vein occlusion. Intracellular adenosine triphosphate（ATP） depletion and subsequent induced endoplasmic reticulum（ER） stress are proposed to be the underlying mechanisms of ischemic retinal cell death. Recently, we found that a naphthalene derivative can inhibit ATPase activity of valosin-containing protein, universally expressed within various types of cells, including retinal neural cells, with strong cytoprotective activity. Based on the chemical structure, we developed novel valosin-containing protein modulators, Kyoto University Substances（KUSs）, that not only inhibit intracellular ATP depletion, but also ameliorate ER stress. Suppressing ER stress by KUSs is associated with neural cell survival in animal models of several neurodegenerative diseases, such as glaucoma and retinal degeneration. Given that a major pathology of ischemic retinal diseases, other than intracellular ATP depletion, is ER stress-induced cell death, KUSs may provide a novel strategy for cell protection in ischemic conditions. Hence, we investigated the efficacy of KUS121 in a rat model of retinal ischemic injury. Intravitreal injections of KUS121, which is clinically preferable route of drug administration in retinal diseases, significantly suppressed inner retinal thinning and retinal cell death, and maintained visual functions. Valosin-containing protein modulation by KUS is a promising novel therapeutic strategy for ischemic retinal diseases.
基金the Science and Technology Foundation of Shanghai Railway Bureau of China, No. B340406052
文摘Sixty elderly patients, viro cluffered from acute stroke and were admitted within a 1-year period to the Department of Geriatrics in the First Affiliated Hospital of School of Medicine, Zhejiang University, China, underwent early rehabilitation in combination with neuroprotective drug therapy. Limb movement, cognitive functions and daily life self-care ability in elderly patients upon admission and discharge were assessed using the Hunt-Hess scale, functional independence measures and mini-mental state examination. The mean duration of hospital stay among the 60 patients was 35 days. Upon discharge, 42 （75%） of the patients exhibited cognitive impairment to varying degrees, and 25 （45%） of the 56 stroke patients who underwent rehabilitation evaluation attained independence in daily living activities, 11 （20%） required intermittent supervision, and 20 （36%） required 24-hour constant supervision during performance of these activities. Results demonstrated that early rehabilitation treatment in combination with neuroprotective therapy for acute stroke was effective.
