Objective In order to characterize the feature of stress response induced by stressor with both physical and psychological natures,the effect of water restriction performed in different experimental modes on the physi...Objective In order to characterize the feature of stress response induced by stressor with both physical and psychological natures,the effect of water restriction performed in different experimental modes on the physiological parameters,psychological behavioral manifestations and brain c-Fos expressions were observed and compared. Methods 58 male Wistar rats were used and randomly divided into three experimental groups (n=18 for each) and a control group (n=4). In control group,the rats were allowed to access drinking water freely at all experimental period. In the experimental groups the water supply to the rats was restricted. In timed water supply (TW) group,the water was supplied twice a day,10 min for each in fixed hours every day. In empty bottle-served (EB) and water-restricted (WR) groups,the water was served only once a day for 10 min,either in the early morning or evening,and in the other time point scheduled for water supply only an empty bottle without water was provided in the EB group and nothing was given in the WR group. The quantities of drank water and eaten food,weight-gaining,and behavior score were observed every day. The serum level of corticosterone was assayed and the rats were sacrificed with fixative perfusion of 3 d,7 d or 14 d respectively,following water restriction (n=6 for each time point in each group). The brain c-Fos expressions were examined with immunohistochemistry. Results The slowing down of weight-gaining,rise of serum corticosterone level,occurrence of psychological behavioral manifestations of unpeaceful restlessness such as exploring and attacking,enhance of c-Fos expression in the subfornical organ (SFO),median preoptic nucleus (MnPO),area postrema (AP),hypothalamic paraventricular nucleus (PVN),supraoptic nucleus (SON),medial (MeA) and central (CeA) amygdaloid nucleus and ventrolateral septum (LSV) were noticed in both EB and WR groups,except the nucleus of solitary tract (NTS) in which the Fos expression was decreased. The changes of Fos expression in most of nuclei in EB group began at day 3,at least persisted till day 7,and backed down at day 14. While in WR group,similar changes started at day 7 and reached its peak at day 14. In TW group,only the concentration of corticosterone at day 7 was slightly increased and the rest indexes observed were unchanged. Conclusion The results indicate that water restriction induces physical as well as psychologi-cal stress responses. And the water restrictions experimentally executed in different modes result in different manifesta-tions of behavioral response and brain immediately early gene expression in discrete brain nuclei/regions.展开更多
DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this...DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.展开更多
Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammaso...Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH.The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms.In this study,a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats.Z-IETD-FMK(0.5,1,2 mg/kg;an inhibitor of caspase-8)was delivered via intravenous(tail vein)injection immediately after subarachnoid hemorrhage.After 12 hours of subarachnoid hemorrhage,western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours,peaked at 24 hours,and then decreased at 72 hours after subarachnoid hemorrhage.Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage.Z-IETDFMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage.The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage.Furthermore,inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3,caspase-1,and interleukin-1βafter subarachnoid hemorrhage.In conclusion,our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation.The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital,School of Medicine,Zhejiang University,China(approval No.2016-193)on February 25,2016.展开更多
Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is diffi...Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.展开更多
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse tra...To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.展开更多
BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.O...BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.展开更多
OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injur...OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.展开更多
BACKGROUND： Exogenous ganglioside-1 （GM1） can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE： To examine the possible mechanisms of exogenous GM1 ...BACKGROUND： Exogenous ganglioside-1 （GM1） can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE： To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING： A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute, Children＇s Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS： A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration （8% O2, 92% N2） for 2 hours, METHODS： All rats were randomly divided into the following groups： GMI, model, and sham operation, with 12 rats each group. Rats in the GM 1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections of GM1 （i.p., 20 mg/kg） at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered （i.p.） the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES： At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS： （1） In the GMI and sham operation groups, growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery （P 〈 0.05）. In all three groups, brain weight of the right hemisphere was significantly less than the left hemisphere, in particular in the model group （P 〈 0.05）. In the GMI group, the weight difference between two hemispheres, as well as the extent of damage in the right hemisphere, was less than the model group （P 〈 0.01 ）. In the sham operation Uoup, brain tissue consisted of integrated structures and ordered cells. In the model group, the cerebral cortex layers of the right hemisphere were not defined, neurons were damaged, and neurons were disarranged in the hippocampal area. In the GM1 group, neurons were dense in the right cerebral cortex and hippocampal area, with no significant change in glial proliferation. （2） The average time of escape latency in the GM1 group was shortened 4 weeks alter surgery, and significantly less than the model group （P 〈 0.05）. In addition, the frequency platform passing in the GMI group was significantly greater than the model group （P 〈 0.01）. CONCLUSION： Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats. This protection may be associated with increased growth-associated protein-43 expression, which is involved in neuronal remodeling processes.展开更多
Background: Dysphagia is common among stroke and acquired brain injury (ABI) patients and may result in aspiration. To reduce the risk of thin liquid aspiration, patients are often restricted to thickened fluids. Ther...Background: Dysphagia is common among stroke and acquired brain injury (ABI) patients and may result in aspiration. To reduce the risk of thin liquid aspiration, patients are often restricted to thickened fluids. There is considerable clinical interest in the risks and benefits of offering oral water intake, in the form of water protocols, to patients with thin-liquid dysphagia. Objectives: A controlled pilot study of a free water protocol was undertaken at Riverview Health Centre, in Winnipeg, Manitoba to assess benefits, feasibility and possible complications of free water protocol. Methods: The study examined 16 individuals with stroke or ABI who were randomly assigned to either a control group on thickened fluids (six subjects) or a treatment group (ten subjects) that followed a free water protocol. The average length of time in the study was 4.3 weeks with a range of 1 - 17 weeks among all participants. Results: Throughout the study, there was no incidence of pneumonia in any of the sixteen participants. No statistically significant difference was noted in the weekly total liquid intake between the treatment group and the control group. Perceived swallowing related care results suggest statistically significant improvements from initial to final measures for both the treatment group (p = 0.004) and the control group (p = 0.02). However, a comparison of the change in both measures, between the treatment and control groups, shows no statistically significant differences. Conclusion: This pilot study suggests the need for larger scale work in order to more accurately identify the effects of free water protocols.展开更多
目的探讨石甘散联合丙戊酸钠对癫痫模型幼鼠脑损伤保护作用及对其认知功能的影响。方法采用随机数表法将60只健康Wistar幼鼠分为对照组、模型组、丙戊酸钠组、石甘散组和联合组共五组,每组各12只。给予对照组幼鼠连续28天腹腔注射1 ml 0...目的探讨石甘散联合丙戊酸钠对癫痫模型幼鼠脑损伤保护作用及对其认知功能的影响。方法采用随机数表法将60只健康Wistar幼鼠分为对照组、模型组、丙戊酸钠组、石甘散组和联合组共五组,每组各12只。给予对照组幼鼠连续28天腹腔注射1 ml 0.9%氯化钠注射液,其余四组幼鼠连续28天腹腔注射1 ml 2 mg/ml戊四氮溶液。建模成功后,给予对照组和模型组幼鼠每日2次0.9%氯化钠注射液灌胃,给予丙戊酸钠组幼鼠每日1次200 mg/kg丙戊酸钠灌胃,给予石甘散组幼鼠每日1次1 g/kg石甘散溶液灌胃,给予联合组幼鼠每日1次200 mg/kg丙戊酸钠灌胃和1次1 g/kg石甘散溶液灌胃,所有幼鼠均连续灌胃治疗28天。治疗结束后进行Morris水迷宫测试,随后处死幼鼠并提取海马组织血液,分别采用TUNEL法和JC-1法检测海马组织神经元凋亡情况和神经元线粒体跨膜电位(Δψm),采用酶联免疫吸附法检测血清神经元特异性烯醇化酶(NSE)。结果(1)对照组幼鼠1-5天的逃避潜伏期显著短于其余四组(P<0.01);丙戊酸钠组、石甘散组和联合组幼鼠1-5天的逃避潜伏期均显著短于模型组;联合组幼鼠1-5天的逃避潜伏期显著短于丙戊酸钠组和石甘散组(P<0.01)。(2)五组幼鼠平台穿越次数比较有显著差异,对照组幼鼠穿越次数最多,其次为联合组,模型组幼鼠穿越次数最少(P<0.01)。(3)五组幼鼠海马组织神经元细胞凋亡比例比较有显著差异,对照组比例最低,其次为联合组,模型组最高(P<0.01)。(4)五组幼鼠海马组织神经元Δψm比较有显著差异,对照组Δψm最高,其次为联合组,模型组最低(P<0.01)。(5)五组幼鼠血清NSE水平比较有显著差异,对照组NSE水平最低,其次为联合组,模型组最高(P<0.01)。(6)丙戊酸钠组和石甘散组幼鼠1-5天的逃避潜伏期、平台穿越次数、海马组织神经元细胞凋亡比例、海马组织神经元Δψm以及血清NSE比较无显著差异(P>0.05)。结论石甘散联合丙戊酸钠能够有效改善癫痫幼鼠认知功能,阻断线粒体异常电位保护线粒体功能,抑制海马组织神经元凋亡,减轻脑损伤程度。展开更多
文摘Objective In order to characterize the feature of stress response induced by stressor with both physical and psychological natures,the effect of water restriction performed in different experimental modes on the physiological parameters,psychological behavioral manifestations and brain c-Fos expressions were observed and compared. Methods 58 male Wistar rats were used and randomly divided into three experimental groups (n=18 for each) and a control group (n=4). In control group,the rats were allowed to access drinking water freely at all experimental period. In the experimental groups the water supply to the rats was restricted. In timed water supply (TW) group,the water was supplied twice a day,10 min for each in fixed hours every day. In empty bottle-served (EB) and water-restricted (WR) groups,the water was served only once a day for 10 min,either in the early morning or evening,and in the other time point scheduled for water supply only an empty bottle without water was provided in the EB group and nothing was given in the WR group. The quantities of drank water and eaten food,weight-gaining,and behavior score were observed every day. The serum level of corticosterone was assayed and the rats were sacrificed with fixative perfusion of 3 d,7 d or 14 d respectively,following water restriction (n=6 for each time point in each group). The brain c-Fos expressions were examined with immunohistochemistry. Results The slowing down of weight-gaining,rise of serum corticosterone level,occurrence of psychological behavioral manifestations of unpeaceful restlessness such as exploring and attacking,enhance of c-Fos expression in the subfornical organ (SFO),median preoptic nucleus (MnPO),area postrema (AP),hypothalamic paraventricular nucleus (PVN),supraoptic nucleus (SON),medial (MeA) and central (CeA) amygdaloid nucleus and ventrolateral septum (LSV) were noticed in both EB and WR groups,except the nucleus of solitary tract (NTS) in which the Fos expression was decreased. The changes of Fos expression in most of nuclei in EB group began at day 3,at least persisted till day 7,and backed down at day 14. While in WR group,similar changes started at day 7 and reached its peak at day 14. In TW group,only the concentration of corticosterone at day 7 was slightly increased and the rest indexes observed were unchanged. Conclusion The results indicate that water restriction induces physical as well as psychologi-cal stress responses. And the water restrictions experimentally executed in different modes result in different manifesta-tions of behavioral response and brain immediately early gene expression in discrete brain nuclei/regions.
基金supported by the grants from Hebei Province Science and Technology Ministry,No.20276102DKey Project of Hebei Province Education Ministry,No.ZD2010106
文摘DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.
基金supported by Clinical Scientific Foundation of Zhejiang Medical Association of China,No.2018ZYC-A09(to HL)
文摘Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH.The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms.In this study,a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats.Z-IETD-FMK(0.5,1,2 mg/kg;an inhibitor of caspase-8)was delivered via intravenous(tail vein)injection immediately after subarachnoid hemorrhage.After 12 hours of subarachnoid hemorrhage,western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours,peaked at 24 hours,and then decreased at 72 hours after subarachnoid hemorrhage.Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage.Z-IETDFMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage.The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage.Furthermore,inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3,caspase-1,and interleukin-1βafter subarachnoid hemorrhage.In conclusion,our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation.The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital,School of Medicine,Zhejiang University,China(approval No.2016-193)on February 25,2016.
文摘Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.
基金supported by a grant for Scientific Research Program from the Health Bureau of Henan Province (No.200202)
文摘To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.
基金the National Natural Science Foundation of China,No. 30973090the Natural Science Foundation of Tianjin,No.09JCZDJC17200
文摘BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.81822050(to QQL),81873321(to HX),81673990(to QQL),81330085(to QS),81730107(to YJW)the Shanghai Municipal Health and Family Planning Commission TCM Research Project of China,No.2018JP014(to HX)+4 种基金the Three-Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals of China,No.16CR1017A(to YJW)the Shanghai Traditional Chinese Medicine Chronic Disease [Malignant Tumor,Bone Degenerative Disease] Clinical Medical Center of China,No.2017ZZ01010(to YJW)the National Ministry of Education Innovation Team of China,No.IRT1270(to YJW)the Innovation Team of Key Fields of the Ministry of Science and Technology of China,No.2015RA4002(to YJW)the Outstanding Principle Investigator Project of Guanghua Hospital,Changning District,Shanghai,China,No.2016-01(to QS),2016-06(to YJW)
文摘OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.
基金supported by the Chongqing Municipal Health Bureau "Effect of ephedrine on neuronal plasticity of hypoxic-ischemic brain damage in neonatal rats" (Grant No. [Yu health science and education (2007) NO.1 (07-2-153)]).
文摘BACKGROUND： Exogenous ganglioside-1 （GM1） can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE： To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING： A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute, Children＇s Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS： A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration （8% O2, 92% N2） for 2 hours, METHODS： All rats were randomly divided into the following groups： GMI, model, and sham operation, with 12 rats each group. Rats in the GM 1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections of GM1 （i.p., 20 mg/kg） at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered （i.p.） the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES： At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS： （1） In the GMI and sham operation groups, growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery （P 〈 0.05）. In all three groups, brain weight of the right hemisphere was significantly less than the left hemisphere, in particular in the model group （P 〈 0.05）. In the GMI group, the weight difference between two hemispheres, as well as the extent of damage in the right hemisphere, was less than the model group （P 〈 0.01 ）. In the sham operation Uoup, brain tissue consisted of integrated structures and ordered cells. In the model group, the cerebral cortex layers of the right hemisphere were not defined, neurons were damaged, and neurons were disarranged in the hippocampal area. In the GM1 group, neurons were dense in the right cerebral cortex and hippocampal area, with no significant change in glial proliferation. （2） The average time of escape latency in the GM1 group was shortened 4 weeks alter surgery, and significantly less than the model group （P 〈 0.05）. In addition, the frequency platform passing in the GMI group was significantly greater than the model group （P 〈 0.01）. CONCLUSION： Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats. This protection may be associated with increased growth-associated protein-43 expression, which is involved in neuronal remodeling processes.
文摘Background: Dysphagia is common among stroke and acquired brain injury (ABI) patients and may result in aspiration. To reduce the risk of thin liquid aspiration, patients are often restricted to thickened fluids. There is considerable clinical interest in the risks and benefits of offering oral water intake, in the form of water protocols, to patients with thin-liquid dysphagia. Objectives: A controlled pilot study of a free water protocol was undertaken at Riverview Health Centre, in Winnipeg, Manitoba to assess benefits, feasibility and possible complications of free water protocol. Methods: The study examined 16 individuals with stroke or ABI who were randomly assigned to either a control group on thickened fluids (six subjects) or a treatment group (ten subjects) that followed a free water protocol. The average length of time in the study was 4.3 weeks with a range of 1 - 17 weeks among all participants. Results: Throughout the study, there was no incidence of pneumonia in any of the sixteen participants. No statistically significant difference was noted in the weekly total liquid intake between the treatment group and the control group. Perceived swallowing related care results suggest statistically significant improvements from initial to final measures for both the treatment group (p = 0.004) and the control group (p = 0.02). However, a comparison of the change in both measures, between the treatment and control groups, shows no statistically significant differences. Conclusion: This pilot study suggests the need for larger scale work in order to more accurately identify the effects of free water protocols.
文摘目的探讨石甘散联合丙戊酸钠对癫痫模型幼鼠脑损伤保护作用及对其认知功能的影响。方法采用随机数表法将60只健康Wistar幼鼠分为对照组、模型组、丙戊酸钠组、石甘散组和联合组共五组,每组各12只。给予对照组幼鼠连续28天腹腔注射1 ml 0.9%氯化钠注射液,其余四组幼鼠连续28天腹腔注射1 ml 2 mg/ml戊四氮溶液。建模成功后,给予对照组和模型组幼鼠每日2次0.9%氯化钠注射液灌胃,给予丙戊酸钠组幼鼠每日1次200 mg/kg丙戊酸钠灌胃,给予石甘散组幼鼠每日1次1 g/kg石甘散溶液灌胃,给予联合组幼鼠每日1次200 mg/kg丙戊酸钠灌胃和1次1 g/kg石甘散溶液灌胃,所有幼鼠均连续灌胃治疗28天。治疗结束后进行Morris水迷宫测试,随后处死幼鼠并提取海马组织血液,分别采用TUNEL法和JC-1法检测海马组织神经元凋亡情况和神经元线粒体跨膜电位(Δψm),采用酶联免疫吸附法检测血清神经元特异性烯醇化酶(NSE)。结果(1)对照组幼鼠1-5天的逃避潜伏期显著短于其余四组(P<0.01);丙戊酸钠组、石甘散组和联合组幼鼠1-5天的逃避潜伏期均显著短于模型组;联合组幼鼠1-5天的逃避潜伏期显著短于丙戊酸钠组和石甘散组(P<0.01)。(2)五组幼鼠平台穿越次数比较有显著差异,对照组幼鼠穿越次数最多,其次为联合组,模型组幼鼠穿越次数最少(P<0.01)。(3)五组幼鼠海马组织神经元细胞凋亡比例比较有显著差异,对照组比例最低,其次为联合组,模型组最高(P<0.01)。(4)五组幼鼠海马组织神经元Δψm比较有显著差异,对照组Δψm最高,其次为联合组,模型组最低(P<0.01)。(5)五组幼鼠血清NSE水平比较有显著差异,对照组NSE水平最低,其次为联合组,模型组最高(P<0.01)。(6)丙戊酸钠组和石甘散组幼鼠1-5天的逃避潜伏期、平台穿越次数、海马组织神经元细胞凋亡比例、海马组织神经元Δψm以及血清NSE比较无显著差异(P>0.05)。结论石甘散联合丙戊酸钠能够有效改善癫痫幼鼠认知功能,阻断线粒体异常电位保护线粒体功能,抑制海马组织神经元凋亡,减轻脑损伤程度。
