MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are...MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.展开更多
Clinical outcomes are positively associated with hematoma absorption.The monocyte-macrophage scavenger receptor,CD163,plays an important role in the metabolism of hemoglobin,and a soluble form of CD163 is present in p...Clinical outcomes are positively associated with hematoma absorption.The monocyte-macrophage scavenger receptor,CD163,plays an important role in the metabolism of hemoglobin,and a soluble form of CD163 is present in plasma and other tissue fluids;therefore,we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage.Patients with intracerebral hemorrhage were divided into high-and low-level groups according to the average CD163 level(1,977.79 ± 832.91 ng/m L).Compared with the high-level group,the low-level group had a significantly slower hematoma absorption rate,and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores.These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.展开更多
BACKGROUND: It has been reported that cerebrovascular disease causes changes in electrocardiogram results. OBJECTIVE: To investigate changes in electrocardiogram results in patients with intracerebral bematoma enlar...BACKGROUND: It has been reported that cerebrovascular disease causes changes in electrocardiogram results. OBJECTIVE: To investigate changes in electrocardiogram results in patients with intracerebral bematoma enlargement. DESIGN, TIME AND SETTING: The present case-retrospective analysis study was performed at the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to October 2006. PARTICIPANTS: A total of 225 intracerebral hemorrhage patients (142 males and 83 females) that were hospitalized at the Department of Neurology were enrolled the present study. The patient selection was in accordance with diagnostic criteria from the Fourth National Cerebrovascular Disease Congress of China in 1995, and diagnosis was confirmed using computed tomography. All patients underwent computed tomography twice within 24 hours following intracerebral hemorrhage, and were subjected to electrocardiogram examination after admission. METHODS: According to hematoma enlargement following intracerebral hemorrhage, all patients were divided into hematoma enlargement (n = 20) and non-hematoma enlargement (n = 205) groups. Because of the large patient number difference between the two groups, the hematoma enlargement group was matched with the non-hematoma enlargement group. Patients meeting these conditions were included in the non-hematoma enlargement group. Finally, 75 patients were included in the final analysis, 19 in the hematoma enlargement group and 56 in the non-hematoma enlargement group. Clinical data from the two groups were statistically analyzed. MAIN OUTCOME MEASURES: The incidence of electrocardiographic abnormalities between the hematoma enlargement and non-hematoma enlargement groups. RESULTS: In the hematoma enlargement group, 15 patients (79%) developed electrocardiographic abnormafities. In the non-hematoma enlargement group, 24 patients (43%) presented with electrocardiographic abnormalities. There were significant differences in electrocardiographic abnormalities between the groups (P 〈 0.01). CONCLUSION: Patients with electrocardiographic abnormalities suffered from hematoma enlargement following admission.展开更多
Objective: To investigate the effects of minimally invasive evacuation of intracranial hematoma on serum SP, SF, vascular endothelial function and inflammatory factors of patients with hypertensive intracerebral hemor...Objective: To investigate the effects of minimally invasive evacuation of intracranial hematoma on serum SP, SF, vascular endothelial function and inflammatory factors of patients with hypertensive intracerebral hemorrhage. Methods: According to random data table method, a total of 120 patients with hypertensive cerebral hemorrhage from September 2016 to May 2017 were divided into observation group and the control group, 60 cases in each group. The control group was treated with conventional treatment;on the basis of conventional treatment, the observation group underwent minimally invasive evacuation of intracranial hematoma. The levels of serum SF, SP, vascular endothelial function and inflammatory factors changes were compared between the two groups before and after the treatment. Results: Before treatment, the levels of serum SP, SF, NO, ET-1, hs-CRP, IL-6, TNF-α in the two groups were not statistically significant. The levels of hs-CRP, IL-6, TNF-α, SF, ET-1 after treatment in two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of SP, NO in the two groups after treatment were significantly higher than before treatment, and the observation group was higher than that the control group with significant difference. Conclusion: The minimally invasive intracranial hematoma evacuation for patients with HICH can effectively improve the levels of SP, SF, inflammatory factors and vascular endothelial function, which is helpful to relieve cerebral edema and lower intracranial pressure, and improve the quality of treatment.展开更多
Spontaneous intracerebral hemorrhage (ICH) accounts for one fifth of all strokes and is associated with an extremely high rate of morbidity and mortality. Affecting greater than 1 million people a year, ICH will leave...Spontaneous intracerebral hemorrhage (ICH) accounts for one fifth of all strokes and is associated with an extremely high rate of morbidity and mortality. Affecting greater than 1 million people a year, ICH will leave the majority of its’ patients significantly disabled or dead. An initially high systolic blood pressure upon presentation is associated with hematoma expansion, peri-hema- toma expansion, and increased mortality. The relationship between blood pressure, the degree of blood pressure control and hematoma expansion has yet to be defined, but the literature has ob- served a relationship between tightly controlled blood pressures and decreased hematoma expansion. There have been many proposed mechanisms to explain this effect. Larger initial hematomas may lend greater hydrostatic forces and this could result in greater total hematoma volume, and greater surrounding edema. Recent literature has suggested that blood pressure reductions in acute ICH may be tolerated because of reduced metabolism, and preserved autoreguation in the peri-hematoma region. The volume of the hematoma is a critical determinant of mortality and functional outcome after intracerebral hemorrhage, and early hematoma growth is an important cause of neurologic deterioration. An increase in volume of more than thirty-three percent is detectable on repeated computed tomography (CT) in thirty-eight percent of patients initially scanned within the first three hours of onset of symptoms;in two thirds of these cases this change is noticeable on CT within the first hour. This supports the hypothesis that early aggressive blood pressure optimization would decrease hematoma size and edema. This is further supported by the fact that patients with high blood pressure and acute intracerebral hemorrhage have worse outcomes than their counterparts. We hypothesize that prompt and aggressive, early blood pressure reduction in emergency department patients with acute spontaneous intracerebral hemorrhage will result in a reduction of early hematoma growth. The study institution is a large urban emergency department and tertiary care stoke center, with over 55,000 emergency department visits per year. This prospective cohort study compared the results and outcomes observed within the enrolled prospective study population, to the results and outcomes of a matched historical cohort population (future patients with intracranial hemorrhage that did not receive the ABC-ICH protocol). Methods and Material: A nicardipine infusion was administered to optimize blood pressure in all patients presenting with intracerebral hemorrhage with a target mean arterial pressure (MAP) of 80 - 110. Hematoma volume (primary outcome measure) was measured on cat scans at time of presentation and at twenty-four hours. The hematoma volume in the enrolled prospective study population was compared to those of a matched cohort (patients with intracranial hemorrhage that did not receive the ABC-ICH protocol following the conclusion of the study). Results: One hundred total patients were enrolled into the study. Fifty patients were enrolled prospectively in the study and matched to a similar group of fifty cohort patients. The difference in the mean change of hematoma volume at twenty-four hours was 7.29 ml (control) and 2.84 ml (study). The result was an absolute decrease in hematoma size of 4.45 ml in the group treated aggressively with nicardapine for blood pressure reduction within one hour of their initial presentation. Conclusions: These results support the previous research suggesting that aggressive blood pressure control in intracerebral hemorrhage reduces hematoma growth, however the clinical benefit of such a reduction will have to be evaluated in ongoing research.展开更多
BACKGROUND: The mechanism of intracerebral hemorrhage (ICH)-induced hemorrhagic brain injury is very complicated, involving the position-occupying effect of cephalophyma, ischemic factors, the toxic effect of hematoma...BACKGROUND: The mechanism of intracerebral hemorrhage (ICH)-induced hemorrhagic brain injury is very complicated, involving the position-occupying effect of cephalophyma, ischemic factors, the toxic effect of hematoma components, the destruction of blood-brain barrier, etc. The expression and effect of hemeoxygenase-1 (HO-1) in the cerebrovascular disease has been paid close attention. OBJECTIVE: To observe the expression of HO-1 and change of superoxide dismutase (SOD) in the peri-hematomal brain tissue of rats following ICH. DESIGN: Randomized controlled animal experiment. SETTING: Department of Neurology, Yijishan Hospital Affiliated to Wannan Medical College. MATERIALS: Forty healthy male SD rats, of clean grade, weighing from 250 to 300 g, were provided by Qinglongshan Animal Farm of Nanjing. The involved 40 rats were randomized into sham-operation group (n =5) and ICH group (n =35), and ICH group was divided into 7 subgroups with 5 rats in each: ICH 6, 12, 24, 48, 72, 100 and 168 hours groups. Rabbit anti-rat HO-1 immunohistochemial kit ( Boster Co., Ltd., Wuhan) and SOD kit (Jiancheng Bioengineering Institute, Nanjing)were used in this experiment. METHODS: This experiment was carried out in the Department of Neurology, Yijishan Hospital Affiliated to Wannan Medical College Between April and July 2005. In the ICH group: Autologous blood of rats was injected into the head of caudate nucleus to create ICH animal models. In the sham-operation group, the same amount of normal saline was injected into the head of caudate nucleus of rats. The brains of rats in each group were harvested at different time points. The hematoma-side brain tissue was cut open in the coronal plane taking hematomal region as center, and the posterior part was fixed with 100 g/L neutral formaldehyde. 100 mg brain tissue was taken from anterior part. The number of positive cells in HO-1 and SOD activity in peri-hematomal brain tissue at different time after ICH were detected by immunohistochemical method and xanthine oxidation method respectively. MAIN OUTCOME MEASURES: ① The expression of HO-1 in the peri-hematomal brain tissue of rats in two groups following ICH.② The expression of SOD activity in the peri-hematomal brain tissue of rats in two groups following ICH. RESULTS: ①The number of HO-1 positive cells in the peri-hematomal brain tissue of rats in two groups following ICH 6, 12, 24, 48, 72, 120 and 168 hours was (11.03±2.01),(16.47±2.98),(25.50±5.65),(51.57±7.05),(47.33±4.73),(26.57±5.12),(7.63±2.17) cells/high-fold visual field , respectively; The number of HO-1 positive cells in the ICH 12-120 hours groups was significantly higher than that of sham-operation group [(6.07±1.85)cells/high-fold visual field, P < 0.01]; The HO-1 positive cells were the most in the ICH 48 hours group and were still expressed a little in the ICH 168 hours group. ② The SOD in the brain tissue of rats at ICH 6, 12, 24, 48, 72, 120 and 168 hours was (404.46±8.14),(396.84±10.97),(387.74±5.32),(356.21±9.27),(307.95±10.15),(357.48±11.28) and (402.98±7.23) kNU/g, respectively; The SOD activity of ICH 12 to 120 hours groups was significantly lower than that of sham-operation group [(415.47±11.44) kNU/g,P < 0.01], and that of ICH 72 hours group was the lowest. There was no significant difference of SOD activity between ICH 168 hours group and sham-operation group (P > 0.05). CONCLUSION: Following ICH, the expression of HO-1 in peri-hematomal brain tissue of rats in two groups is obviously increased, but the antioxidant ability of brain tissue is decreased. The changes of both maybe play an important role in the formation of ICH-induced hemorrhagic brain injury.展开更多
To study the relationship between incidence and time course of traumatic intracerebral hematoma enlargement and that between hematoma irregular rate (IR) and hematoma enlargement after brain injury.Methods After brain...To study the relationship between incidence and time course of traumatic intracerebral hematoma enlargement and that between hematoma irregular rate (IR) and hematoma enlargement after brain injury.Methods After brain injury,164 cases with traumatic supratentorial intracerebral hematoma were examined by cranial CT scan within 72 hours thereafter reexamined 120 hours there after so as to compare the hematoma volumes (V1 and V2) and analyze the relation between hematoma IR and hematoma enlargement.Results After brain injury,enlargement of hematoma was confirmed in 70 cases (42.7%),in which the cutpoint for hematoma enlargement was determined as V2/V1=1.45 by using receiver operating characteristic curves (ROC).Hematoma IR had positive correlation with hematoma enlargement (r=0.857,P<0.01).Conclusion Since the incidence of traumatic hematoma enlargement is high,we can tell the possibility of hematoma enlargement based on hematoma IR in order to make a timely reexamination of CT scan and apply active treatments.7 refs,1 tab.展开更多
AIM: This study aimed to expound the individual idea of micro-invasive surgery from pre-operative preparation, intra-operative processing and post-operative management. METHODS: Pre-operative preparation was improve...AIM: This study aimed to expound the individual idea of micro-invasive surgery from pre-operative preparation, intra-operative processing and post-operative management. METHODS: Pre-operative preparation was improved by analyzing pathological factors and hematoma property, and considering patients' age, basic disease, blood pressure control, with persistent haemorrhagia/rehaemorrhagia or not, operative occasion choice, positioning and other procedures. In the surgery, positioner was used. Initial aspiration volume was cautiously controlled. After operation, vital signs of patients were kept stable by cautiously using hematoma liquefacient and combining with free radical scavenger. RESULTS: The core content of individual micro-invasive surgery was mainly to relieve intracranial pressure. Under the condition of sufficient pre-operative preparation known by patients' family members, precise positioning was determined and individual therapeutic regimen was made. Meanwhile, caution should be taken in hematoma aspiration. Liquefaction and drainage should be paid more attention, and complications were processed actively. CONCLUSION: During the process of micro-invasive evacuation of intracranial hematoma for treating cerebral hemorrhage, attention should be paid to analyzing cerebral hematoma etiology and pathophysiological mechanism, and individual idea should be considered in surgical treatment aiming at patients' concrete disease condition.展开更多
Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse differen...Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurologicalneurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it's important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery.展开更多
Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain parenchyma.The PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enz...Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain parenchyma.The PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enzyme-linked receptors and has many biological functions in mammals.It plays a key role in neuronal metabolism,gene expression regulation,and tissue homeostasis in the healthy and diseased brain.Methods In the present study,the role of the PI3K/AKT/mTOR pathway inhibitor chrysophanol(CPH)(10 mg/kg and 20 mg/kg,orally)in the improvement of ICH-associated neurological defects in rats was investigated.Autologous blood(20µL/5 min/unilateral/intracerebroventricular)mimics ICH-like defects involving cellular and molecular dysfunction and neurotransmitter imbalance.The current study also included various behavioral assessments to examine cognition,memory,and motor and neuromuscular coordination.The protein expression levels of PI3K,AKT,and mTOR as well as myelin basic protein and apoptotic markers,such as Bax,Bcl-2,and caspase-3,were examined using ELISA kits.Furthermore,the levels of various neuroinflammatory cytokines and oxidative stress markers were assessed.Additionally,the neurological severity score,brain water content,gross brain pathology,and hematoma size were used to indicate neurological function and brain edema.Results CPH was found to be neuroprotective by restoring neurobehavioral alterations and significantly reducing the elevated PI3K,AKT,and mTOR protein levels,and modulating the apoptotic markers such as Bax,Bcl-2,and caspase-3 in rat brain homogenate.CPH substantially reduced the inflammatory cytokines like interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.CPH administration restored the neurotransmitters GABA,glutamate,acetylcholine,dopamine,and various oxidative stress markers.Conclusion Our results show that CPH may be a promising therapeutic approach for overcoming neuronal damage caused by the overexpression of the PI3K/AKT/mTOR signaling pathway in ICH-induced neurological dysfunctions in rats.展开更多
In Alzheimer’s disease and ischemic stroke,intranasal insulin can act as a neuroprotective agent.However,whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanism...In Alzheimer’s disease and ischemic stroke,intranasal insulin can act as a neuroprotective agent.However,whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanisms remain poorly understood.In this study,a mouse model of autologous blood-induced intracerebral hemorrhage was treated with 0.5,1,or 2 IU insulin via intranasal delivery,twice per day,until 24 or 72 hours after surgery.Compared with saline treatment,1 IU intranasal insulin treatment significantly reduced hematoma volume and brain edema after cerebral hemorrhage,decreased blood-brain barrier permeability and neuronal degeneration damage,reduced neurobehavioral deficits,and improved the survival rate of mice.Expression levels of p-AKT and p-GSK3βwere significantly increased in the perihematoma tissues after intranasal insulin therapy.Our findings suggest that intranasal insulin therapy can protect the neurological function of mice after intracerebral hemorrhage through the AKT/GSK3βsignaling pathway.The study was approved by the Ethics Committee of the North Sichuan Medical College of China(approval No.NSMC(A)2019(01))on January 7,2019.展开更多
The corticospinal tract (CST) is a major neuronal tract of motor function in the human brain (York, 1987; Davidoff, 1990; Jang, 2014). Recovery of an injured CST is one of the motor recovery mechanisms in stroke p...The corticospinal tract (CST) is a major neuronal tract of motor function in the human brain (York, 1987; Davidoff, 1990; Jang, 2014). Recovery of an injured CST is one of the motor recovery mechanisms in stroke patients (Hendricks et al., 2003; Jang et al., 2006, 2007; Swayne et al., 2008; Kwon et al., 2011, 2013; Kwon and Jang, 2012; Yeo and Jang, 2013; Rong et al., 2014). Diffusion tensor tractography (DTT), derived from diffusion tensor imaging (DTI), and transcra- nial magnetic stimulation (TMS) have been widely used in demonstrating the recovery of an injured CST (Hendricks et al., 2003; Jang et al., 2006, 2007; Swayne et al., 2008; Pannek et al., 2009; Kwon et al., 2011, 2013; Kwon and Jang, 2012; Yeo and Jang, 2013; Rong et al., 2014). DTT has the advan- tage of enabling visualization of the architecture and integ- rity of the CST at the subcortical level in three dimensions (Mori et al., 1999; Kunimatsu et al., 2004).展开更多
Lipid peroxidation mediated by oxygen radical is one of the main mechanisms underlying secondary brain injury. Among all vitamin E compounds, α-tocopherol shows the most prominent antioxidative effects. It plays an i...Lipid peroxidation mediated by oxygen radical is one of the main mechanisms underlying secondary brain injury. Among all vitamin E compounds, α-tocopherol shows the most prominent antioxidative effects. It plays an important role in cell aging and injury. However, there has been no report regarding the effects of α-tocopherol on changes in brain tissue morphology after intracerebral hemorrhage (ICH), cerebral edema, or the expression of Bax and Bcl-2 proteins. We use SD rats to carry out the related studies;based on the atlas of SD rats, the caudate nucleus was positioned using a stereotaxic apparatus, and 50 μl autologous tail artery blood was injected to caudate nucleus in the ICH and α-tocopherol groups to establish ICH model. Rats in the sham surgery group received the same volume of saline in the caudate nucleus. Rats in the α-tocopherol group received intraperitoneal injections of α-tocopherol at 600 mg/kg every day. Rats in the ICH group and sham surgery group received the same amount of saline at the same times as those in the α-tocopherol group. We observed some interesting results: comparisons of brain tissue sections of rats from different groups showed that brain tissue damage and functional neurological deficits among rats from the α-tocopherol group were less pronounced than in the ICH group. Wet weight/ dry weight measurement showed that rats from the α-tocopherol group exhibited less cerebral edema than those in the ICH group. Rats from the α-tocopherol group showed less Bax expression and more Bcl-2 expression than those in the ICH group.展开更多
Objective:The purpose of this study was to find a suitable model to evaluate the relationship between temperature and intracerebral hemorrhage(ICH)and explore the effects of cold spells and heat waves on the clinicopa...Objective:The purpose of this study was to find a suitable model to evaluate the relationship between temperature and intracerebral hemorrhage(ICH)and explore the effects of cold spells and heat waves on the clinicopathological parameters of ICH patients.Methods:We conducted a retrospective study based on the ICH admission in the First Affiliated Hospital of Harbin Medical University from 2015 to 2020(N=11124).The relationship between different seasons and the number of patients with ICH was explored.Poisson Akaike information criterion(AIC)was used to select the optimal model for temperature and ICH.Binary logistic regression analysis was used to investigate the association between extreme temperatures and clinicopathological features.Results:Hospital admissions for patients with ICH showed monthly changes.The optimal cold spell was defined as the daily average temperature<3rd percentile,lasting for five days,while the optimal heat wave was defined as the daily average temperature>97th percentile,lasting for three days.Based on the generalized extreme weather model,cold climate significantly increased the risk of hematoma volume expansion(OR 1.003;95%CI:1.000-1.005,P=0.047).In the optimal model,the occurrence of cold spells and heat waves increased the risk of midline shift in both conditions(OR 1.067;95%CI:1.021-1.115,P=0.004;OR 1.077;95%CI:1.030-1.127,P=0.001).Conclusion:Our study shows that seasonal cold spells and heat waves are essential factors affecting ICH severity,and targeted preventive measures should be taken to minimize the pathological impacts.展开更多
基金supported by Science and Technology Innovation Enhancement Project of Army Medical University(to LX).
文摘MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.
文摘Clinical outcomes are positively associated with hematoma absorption.The monocyte-macrophage scavenger receptor,CD163,plays an important role in the metabolism of hemoglobin,and a soluble form of CD163 is present in plasma and other tissue fluids;therefore,we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage.Patients with intracerebral hemorrhage were divided into high-and low-level groups according to the average CD163 level(1,977.79 ± 832.91 ng/m L).Compared with the high-level group,the low-level group had a significantly slower hematoma absorption rate,and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores.These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.
基金the National Natural Science Foundation of China, No. 30570628, 30770751
文摘BACKGROUND: It has been reported that cerebrovascular disease causes changes in electrocardiogram results. OBJECTIVE: To investigate changes in electrocardiogram results in patients with intracerebral bematoma enlargement. DESIGN, TIME AND SETTING: The present case-retrospective analysis study was performed at the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to October 2006. PARTICIPANTS: A total of 225 intracerebral hemorrhage patients (142 males and 83 females) that were hospitalized at the Department of Neurology were enrolled the present study. The patient selection was in accordance with diagnostic criteria from the Fourth National Cerebrovascular Disease Congress of China in 1995, and diagnosis was confirmed using computed tomography. All patients underwent computed tomography twice within 24 hours following intracerebral hemorrhage, and were subjected to electrocardiogram examination after admission. METHODS: According to hematoma enlargement following intracerebral hemorrhage, all patients were divided into hematoma enlargement (n = 20) and non-hematoma enlargement (n = 205) groups. Because of the large patient number difference between the two groups, the hematoma enlargement group was matched with the non-hematoma enlargement group. Patients meeting these conditions were included in the non-hematoma enlargement group. Finally, 75 patients were included in the final analysis, 19 in the hematoma enlargement group and 56 in the non-hematoma enlargement group. Clinical data from the two groups were statistically analyzed. MAIN OUTCOME MEASURES: The incidence of electrocardiographic abnormalities between the hematoma enlargement and non-hematoma enlargement groups. RESULTS: In the hematoma enlargement group, 15 patients (79%) developed electrocardiographic abnormafities. In the non-hematoma enlargement group, 24 patients (43%) presented with electrocardiographic abnormalities. There were significant differences in electrocardiographic abnormalities between the groups (P 〈 0.01). CONCLUSION: Patients with electrocardiographic abnormalities suffered from hematoma enlargement following admission.
文摘Objective: To investigate the effects of minimally invasive evacuation of intracranial hematoma on serum SP, SF, vascular endothelial function and inflammatory factors of patients with hypertensive intracerebral hemorrhage. Methods: According to random data table method, a total of 120 patients with hypertensive cerebral hemorrhage from September 2016 to May 2017 were divided into observation group and the control group, 60 cases in each group. The control group was treated with conventional treatment;on the basis of conventional treatment, the observation group underwent minimally invasive evacuation of intracranial hematoma. The levels of serum SF, SP, vascular endothelial function and inflammatory factors changes were compared between the two groups before and after the treatment. Results: Before treatment, the levels of serum SP, SF, NO, ET-1, hs-CRP, IL-6, TNF-α in the two groups were not statistically significant. The levels of hs-CRP, IL-6, TNF-α, SF, ET-1 after treatment in two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of SP, NO in the two groups after treatment were significantly higher than before treatment, and the observation group was higher than that the control group with significant difference. Conclusion: The minimally invasive intracranial hematoma evacuation for patients with HICH can effectively improve the levels of SP, SF, inflammatory factors and vascular endothelial function, which is helpful to relieve cerebral edema and lower intracranial pressure, and improve the quality of treatment.
文摘Spontaneous intracerebral hemorrhage (ICH) accounts for one fifth of all strokes and is associated with an extremely high rate of morbidity and mortality. Affecting greater than 1 million people a year, ICH will leave the majority of its’ patients significantly disabled or dead. An initially high systolic blood pressure upon presentation is associated with hematoma expansion, peri-hema- toma expansion, and increased mortality. The relationship between blood pressure, the degree of blood pressure control and hematoma expansion has yet to be defined, but the literature has ob- served a relationship between tightly controlled blood pressures and decreased hematoma expansion. There have been many proposed mechanisms to explain this effect. Larger initial hematomas may lend greater hydrostatic forces and this could result in greater total hematoma volume, and greater surrounding edema. Recent literature has suggested that blood pressure reductions in acute ICH may be tolerated because of reduced metabolism, and preserved autoreguation in the peri-hematoma region. The volume of the hematoma is a critical determinant of mortality and functional outcome after intracerebral hemorrhage, and early hematoma growth is an important cause of neurologic deterioration. An increase in volume of more than thirty-three percent is detectable on repeated computed tomography (CT) in thirty-eight percent of patients initially scanned within the first three hours of onset of symptoms;in two thirds of these cases this change is noticeable on CT within the first hour. This supports the hypothesis that early aggressive blood pressure optimization would decrease hematoma size and edema. This is further supported by the fact that patients with high blood pressure and acute intracerebral hemorrhage have worse outcomes than their counterparts. We hypothesize that prompt and aggressive, early blood pressure reduction in emergency department patients with acute spontaneous intracerebral hemorrhage will result in a reduction of early hematoma growth. The study institution is a large urban emergency department and tertiary care stoke center, with over 55,000 emergency department visits per year. This prospective cohort study compared the results and outcomes observed within the enrolled prospective study population, to the results and outcomes of a matched historical cohort population (future patients with intracranial hemorrhage that did not receive the ABC-ICH protocol). Methods and Material: A nicardipine infusion was administered to optimize blood pressure in all patients presenting with intracerebral hemorrhage with a target mean arterial pressure (MAP) of 80 - 110. Hematoma volume (primary outcome measure) was measured on cat scans at time of presentation and at twenty-four hours. The hematoma volume in the enrolled prospective study population was compared to those of a matched cohort (patients with intracranial hemorrhage that did not receive the ABC-ICH protocol following the conclusion of the study). Results: One hundred total patients were enrolled into the study. Fifty patients were enrolled prospectively in the study and matched to a similar group of fifty cohort patients. The difference in the mean change of hematoma volume at twenty-four hours was 7.29 ml (control) and 2.84 ml (study). The result was an absolute decrease in hematoma size of 4.45 ml in the group treated aggressively with nicardapine for blood pressure reduction within one hour of their initial presentation. Conclusions: These results support the previous research suggesting that aggressive blood pressure control in intracerebral hemorrhage reduces hematoma growth, however the clinical benefit of such a reduction will have to be evaluated in ongoing research.
文摘BACKGROUND: The mechanism of intracerebral hemorrhage (ICH)-induced hemorrhagic brain injury is very complicated, involving the position-occupying effect of cephalophyma, ischemic factors, the toxic effect of hematoma components, the destruction of blood-brain barrier, etc. The expression and effect of hemeoxygenase-1 (HO-1) in the cerebrovascular disease has been paid close attention. OBJECTIVE: To observe the expression of HO-1 and change of superoxide dismutase (SOD) in the peri-hematomal brain tissue of rats following ICH. DESIGN: Randomized controlled animal experiment. SETTING: Department of Neurology, Yijishan Hospital Affiliated to Wannan Medical College. MATERIALS: Forty healthy male SD rats, of clean grade, weighing from 250 to 300 g, were provided by Qinglongshan Animal Farm of Nanjing. The involved 40 rats were randomized into sham-operation group (n =5) and ICH group (n =35), and ICH group was divided into 7 subgroups with 5 rats in each: ICH 6, 12, 24, 48, 72, 100 and 168 hours groups. Rabbit anti-rat HO-1 immunohistochemial kit ( Boster Co., Ltd., Wuhan) and SOD kit (Jiancheng Bioengineering Institute, Nanjing)were used in this experiment. METHODS: This experiment was carried out in the Department of Neurology, Yijishan Hospital Affiliated to Wannan Medical College Between April and July 2005. In the ICH group: Autologous blood of rats was injected into the head of caudate nucleus to create ICH animal models. In the sham-operation group, the same amount of normal saline was injected into the head of caudate nucleus of rats. The brains of rats in each group were harvested at different time points. The hematoma-side brain tissue was cut open in the coronal plane taking hematomal region as center, and the posterior part was fixed with 100 g/L neutral formaldehyde. 100 mg brain tissue was taken from anterior part. The number of positive cells in HO-1 and SOD activity in peri-hematomal brain tissue at different time after ICH were detected by immunohistochemical method and xanthine oxidation method respectively. MAIN OUTCOME MEASURES: ① The expression of HO-1 in the peri-hematomal brain tissue of rats in two groups following ICH.② The expression of SOD activity in the peri-hematomal brain tissue of rats in two groups following ICH. RESULTS: ①The number of HO-1 positive cells in the peri-hematomal brain tissue of rats in two groups following ICH 6, 12, 24, 48, 72, 120 and 168 hours was (11.03±2.01),(16.47±2.98),(25.50±5.65),(51.57±7.05),(47.33±4.73),(26.57±5.12),(7.63±2.17) cells/high-fold visual field , respectively; The number of HO-1 positive cells in the ICH 12-120 hours groups was significantly higher than that of sham-operation group [(6.07±1.85)cells/high-fold visual field, P < 0.01]; The HO-1 positive cells were the most in the ICH 48 hours group and were still expressed a little in the ICH 168 hours group. ② The SOD in the brain tissue of rats at ICH 6, 12, 24, 48, 72, 120 and 168 hours was (404.46±8.14),(396.84±10.97),(387.74±5.32),(356.21±9.27),(307.95±10.15),(357.48±11.28) and (402.98±7.23) kNU/g, respectively; The SOD activity of ICH 12 to 120 hours groups was significantly lower than that of sham-operation group [(415.47±11.44) kNU/g,P < 0.01], and that of ICH 72 hours group was the lowest. There was no significant difference of SOD activity between ICH 168 hours group and sham-operation group (P > 0.05). CONCLUSION: Following ICH, the expression of HO-1 in peri-hematomal brain tissue of rats in two groups is obviously increased, but the antioxidant ability of brain tissue is decreased. The changes of both maybe play an important role in the formation of ICH-induced hemorrhagic brain injury.
文摘To study the relationship between incidence and time course of traumatic intracerebral hematoma enlargement and that between hematoma irregular rate (IR) and hematoma enlargement after brain injury.Methods After brain injury,164 cases with traumatic supratentorial intracerebral hematoma were examined by cranial CT scan within 72 hours thereafter reexamined 120 hours there after so as to compare the hematoma volumes (V1 and V2) and analyze the relation between hematoma IR and hematoma enlargement.Results After brain injury,enlargement of hematoma was confirmed in 70 cases (42.7%),in which the cutpoint for hematoma enlargement was determined as V2/V1=1.45 by using receiver operating characteristic curves (ROC).Hematoma IR had positive correlation with hematoma enlargement (r=0.857,P<0.01).Conclusion Since the incidence of traumatic hematoma enlargement is high,we can tell the possibility of hematoma enlargement based on hematoma IR in order to make a timely reexamination of CT scan and apply active treatments.7 refs,1 tab.
基金the National Natural Science Foundation of China, No. 3057062830770751
文摘AIM: This study aimed to expound the individual idea of micro-invasive surgery from pre-operative preparation, intra-operative processing and post-operative management. METHODS: Pre-operative preparation was improved by analyzing pathological factors and hematoma property, and considering patients' age, basic disease, blood pressure control, with persistent haemorrhagia/rehaemorrhagia or not, operative occasion choice, positioning and other procedures. In the surgery, positioner was used. Initial aspiration volume was cautiously controlled. After operation, vital signs of patients were kept stable by cautiously using hematoma liquefacient and combining with free radical scavenger. RESULTS: The core content of individual micro-invasive surgery was mainly to relieve intracranial pressure. Under the condition of sufficient pre-operative preparation known by patients' family members, precise positioning was determined and individual therapeutic regimen was made. Meanwhile, caution should be taken in hematoma aspiration. Liquefaction and drainage should be paid more attention, and complications were processed actively. CONCLUSION: During the process of micro-invasive evacuation of intracranial hematoma for treating cerebral hemorrhage, attention should be paid to analyzing cerebral hematoma etiology and pathophysiological mechanism, and individual idea should be considered in surgical treatment aiming at patients' concrete disease condition.
文摘Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurologicalneurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it's important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery.
基金The authors express their gratitude to Chairman,Mr.Parveen Garg and Director,Dr.G.D.Gupta,ISF College of Pharmacy,Moga(Punjab),India,for their great support.
文摘Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain parenchyma.The PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enzyme-linked receptors and has many biological functions in mammals.It plays a key role in neuronal metabolism,gene expression regulation,and tissue homeostasis in the healthy and diseased brain.Methods In the present study,the role of the PI3K/AKT/mTOR pathway inhibitor chrysophanol(CPH)(10 mg/kg and 20 mg/kg,orally)in the improvement of ICH-associated neurological defects in rats was investigated.Autologous blood(20µL/5 min/unilateral/intracerebroventricular)mimics ICH-like defects involving cellular and molecular dysfunction and neurotransmitter imbalance.The current study also included various behavioral assessments to examine cognition,memory,and motor and neuromuscular coordination.The protein expression levels of PI3K,AKT,and mTOR as well as myelin basic protein and apoptotic markers,such as Bax,Bcl-2,and caspase-3,were examined using ELISA kits.Furthermore,the levels of various neuroinflammatory cytokines and oxidative stress markers were assessed.Additionally,the neurological severity score,brain water content,gross brain pathology,and hematoma size were used to indicate neurological function and brain edema.Results CPH was found to be neuroprotective by restoring neurobehavioral alterations and significantly reducing the elevated PI3K,AKT,and mTOR protein levels,and modulating the apoptotic markers such as Bax,Bcl-2,and caspase-3 in rat brain homogenate.CPH substantially reduced the inflammatory cytokines like interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.CPH administration restored the neurotransmitters GABA,glutamate,acetylcholine,dopamine,and various oxidative stress markers.Conclusion Our results show that CPH may be a promising therapeutic approach for overcoming neuronal damage caused by the overexpression of the PI3K/AKT/mTOR signaling pathway in ICH-induced neurological dysfunctions in rats.
基金supported by the National Natural Science Foundation of China,No.81971220a grant from the Science and Technology Department of Sichuan Province of China,No.2018JY0236(both to GHJ)。
文摘In Alzheimer’s disease and ischemic stroke,intranasal insulin can act as a neuroprotective agent.However,whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanisms remain poorly understood.In this study,a mouse model of autologous blood-induced intracerebral hemorrhage was treated with 0.5,1,or 2 IU insulin via intranasal delivery,twice per day,until 24 or 72 hours after surgery.Compared with saline treatment,1 IU intranasal insulin treatment significantly reduced hematoma volume and brain edema after cerebral hemorrhage,decreased blood-brain barrier permeability and neuronal degeneration damage,reduced neurobehavioral deficits,and improved the survival rate of mice.Expression levels of p-AKT and p-GSK3βwere significantly increased in the perihematoma tissues after intranasal insulin therapy.Our findings suggest that intranasal insulin therapy can protect the neurological function of mice after intracerebral hemorrhage through the AKT/GSK3βsignaling pathway.The study was approved by the Ethics Committee of the North Sichuan Medical College of China(approval No.NSMC(A)2019(01))on January 7,2019.
基金supported by the DIGIST R&D Program of the Ministry of Science,ICT and Future Planning(15-BD-0401)
文摘The corticospinal tract (CST) is a major neuronal tract of motor function in the human brain (York, 1987; Davidoff, 1990; Jang, 2014). Recovery of an injured CST is one of the motor recovery mechanisms in stroke patients (Hendricks et al., 2003; Jang et al., 2006, 2007; Swayne et al., 2008; Kwon et al., 2011, 2013; Kwon and Jang, 2012; Yeo and Jang, 2013; Rong et al., 2014). Diffusion tensor tractography (DTT), derived from diffusion tensor imaging (DTI), and transcra- nial magnetic stimulation (TMS) have been widely used in demonstrating the recovery of an injured CST (Hendricks et al., 2003; Jang et al., 2006, 2007; Swayne et al., 2008; Pannek et al., 2009; Kwon et al., 2011, 2013; Kwon and Jang, 2012; Yeo and Jang, 2013; Rong et al., 2014). DTT has the advan- tage of enabling visualization of the architecture and integ- rity of the CST at the subcortical level in three dimensions (Mori et al., 1999; Kunimatsu et al., 2004).
文摘Lipid peroxidation mediated by oxygen radical is one of the main mechanisms underlying secondary brain injury. Among all vitamin E compounds, α-tocopherol shows the most prominent antioxidative effects. It plays an important role in cell aging and injury. However, there has been no report regarding the effects of α-tocopherol on changes in brain tissue morphology after intracerebral hemorrhage (ICH), cerebral edema, or the expression of Bax and Bcl-2 proteins. We use SD rats to carry out the related studies;based on the atlas of SD rats, the caudate nucleus was positioned using a stereotaxic apparatus, and 50 μl autologous tail artery blood was injected to caudate nucleus in the ICH and α-tocopherol groups to establish ICH model. Rats in the sham surgery group received the same volume of saline in the caudate nucleus. Rats in the α-tocopherol group received intraperitoneal injections of α-tocopherol at 600 mg/kg every day. Rats in the ICH group and sham surgery group received the same amount of saline at the same times as those in the α-tocopherol group. We observed some interesting results: comparisons of brain tissue sections of rats from different groups showed that brain tissue damage and functional neurological deficits among rats from the α-tocopherol group were less pronounced than in the ICH group. Wet weight/ dry weight measurement showed that rats from the α-tocopherol group exhibited less cerebral edema than those in the ICH group. Rats from the α-tocopherol group showed less Bax expression and more Bcl-2 expression than those in the ICH group.
基金supported by the National Natural Science Foundations of China(81971135)Natural Science Foundations of Heilongjiang(YQ2020H014)+1 种基金the“Chunhui Plan”of the Ministry of Education(HLJ2019009)Distinguished Young Foundations of the First Affiliated Hospital of Harbin Medical University(HYD2020JQ0014).
文摘Objective:The purpose of this study was to find a suitable model to evaluate the relationship between temperature and intracerebral hemorrhage(ICH)and explore the effects of cold spells and heat waves on the clinicopathological parameters of ICH patients.Methods:We conducted a retrospective study based on the ICH admission in the First Affiliated Hospital of Harbin Medical University from 2015 to 2020(N=11124).The relationship between different seasons and the number of patients with ICH was explored.Poisson Akaike information criterion(AIC)was used to select the optimal model for temperature and ICH.Binary logistic regression analysis was used to investigate the association between extreme temperatures and clinicopathological features.Results:Hospital admissions for patients with ICH showed monthly changes.The optimal cold spell was defined as the daily average temperature<3rd percentile,lasting for five days,while the optimal heat wave was defined as the daily average temperature>97th percentile,lasting for three days.Based on the generalized extreme weather model,cold climate significantly increased the risk of hematoma volume expansion(OR 1.003;95%CI:1.000-1.005,P=0.047).In the optimal model,the occurrence of cold spells and heat waves increased the risk of midline shift in both conditions(OR 1.067;95%CI:1.021-1.115,P=0.004;OR 1.077;95%CI:1.030-1.127,P=0.001).Conclusion:Our study shows that seasonal cold spells and heat waves are essential factors affecting ICH severity,and targeted preventive measures should be taken to minimize the pathological impacts.