Relationship of matrix metallo proteinase-9 dynamic expression at different time points with brain edema after cerebral hemorrhage
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Objective To study the effect of dynamic expression at different time points of metallo proteinase-9 on brain edema after cerebral hemorrhage. Methods Serum levels of MMP-9 in 90 patients with brain hemorrhage and 80 normal patients were detected by radioimmunoassay on 24 h、72 h、7 d and 14 d.The relationship between levels of MMP-9 and brain edema after cerebral hemorrhage.Results Brain edema went up to the peak at 72 h and slowly decline after it. At 24 h, the serum level of MMP-9 were significantly higher, and reached the peak at 72 h according to the peak of cerebral edema, and then decreased significantly after 7 d. Cerebral hemorrhage group compared with the control group were significantly higher(P＜0.01). The level of MMP-9 close to normal levels on 14 d. MMP-9 was positive correlated with edema volume and edema ratioat 24 h and 72 h (P=0.01).Conclusions Serum MMP-9 dynamic changes over time after cerebral hemorrhage. The level of MMP-9 was correlated with the brain edema volume and had more stronger correlation with relative size of brain edema. MMP-9 was correlated with inflammation after cerebral hemorrhage.
Key words:
Cerebral hemorrhage; Brain edema; Matrix metallo proteinases-9Keywords:
Brain Edema
Cerebral edema
Objective:To discuss the expression of nimodipine on AQP4 and MMP-9 mRNA in early cerebral hemorrhage surrounding tissue and the relationship of secondary brain edema caused by cerebral hemorrhage and AQP4、MMP-9.Methods:Cerebral hemorrhage model of rats were divided into control group,cerebral hemorrhage group and nimodipine group.The water content of brain,AQP and MMP-9 mRNA were observed on 6h,1d,3d,5d,7d after intracerebral hemorrhage.Results:(1) On 3d in the ICH group,the brain water content peaked and on 7d it decreased but still higher than normal.On 3d in the nimodipine group,the brain water content peaked but still lower than ICH group.(2)AQP4 and MMP-9 of cerebral hemorrhage group was higher than that of control group at five points,whose expression gradually increased,peaked on 3d,obviously decreased on 7d.(3)Rat's Brain edema degree and expression of AQP4 and MMP-9 in nimodipine group were less than those in cerebral hemorrhage group,whose expression gradually increased,peaked on 3d.(4)The degree of intracerebral hemorrhage edema and AQP4 and MMP-9 mRNA were positively correlated.Conclusion:(1)MMP-9 and AQP4 involved in the process of hemorrhagic brain edema damage.(2)Nimodipine can inhibit the expression of AQP4 and MMP-9 so as to reduce the degree of brain edema.
Nimodipine
Brain Edema
Cerebral edema
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Objective: To study the changes of MMP-2/9expression around hematoma in cerebral hemorrhage (CH) and the relationship with vasogenic brain edema(VBE). Methods: ① Sixty Wistar rats were randomly divided into CH group and control group. The time(6h,24h,48h,72h and 120h) was set for three groups.②Brain water content(BWC) was determined by comparison of wet and dry weight; The BBB opening was evaluated by the evans blue extravasation method; The expression of MMP-2/9 protein in the CH rat brain was detected by immunohistochemistry. Results: ①The EB content in CH group was much higher than that of the control group. ②Serious brain edema happened at 6h after the rat cerebral hemorrhage with the peak at 72h.③We found there were a few MMP-2 protein positive cells in control group with the peak at 6h in CH group, and there were much more positive cells in CH group than in control group at every time point.④There were few positive cues / cells of MMP-9 protein expression, with the peak at 48h in CH group and much more positive cells than control group at every time point. Conclusions: The release and activation of -2/9 around hematoma in CH is one of the factors of brain edema forming, and can result in the form of VBE.
Extravasation
Brain Edema
Cerebral edema
Brain tissue
Evans Blue
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Objective To investigate the expression of MMP-9 in rat brain of intracerebral hemorrhage(ICH),and to study the correlation MMP-9 and brain edema.Methods ICH rat model was made by stereotactic technique,and sham injections served as controls.We measured brain water content,and MMP-9 expression after ICH.Results The brain edema and MMP-9 expression reached the maximum after ICH form 24 h to 72 h.There are marked differences compared with the sham.Conclusion The expression of MMP-9 at higher level and brain edema formation were synchronization at progress.MMP-9 were the key substance which induced the brain edema.
Brain Edema
Cerebral edema
Rat model
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Objective edaravone on brain after focal cerebral ischemia of matrix metalloproteinase 9(MMP-9) expression,of edaravone on ischemic brain tissue in rats.Methods Male rats were randomly divided into 3 groups:sham operation group(A group,10 rats),saline group(B group,middle cerebral artery occlusion after 3 h 6 h 12 h 24 h 48 h 72 h 96 h 7 time points,each 10),edaravone treatment group(C group,with the B group),edaravone intervent after operation.Brain water content were measured;PCR detected mRNA.Results Group B MCAO rats showed an upward trend in brain water content,peak at 48h,each time point were higher than the A group(P0.05).At the same time,MMP-9mRNA expression and brain water content showed the same trend,indicating that the expression of MMP-9mRNA and brain tissue water content were positively correlated.B group and C group,brain water content significantly decreased(P0.05);MMP-9mRNA was significantly lower(P0.05).Conclusion Cerebral ischemia MMP-9 expression and cerebral edema were correlated,suggesting that:MMP-9 may be involved in brain ischemic brain edema.Edaravone can effectively inhibit the overexpression of MMP-9 and cerebral edema and improve neurological function.
Edaravone
Brain Edema
Cerebral edema
Brain tissue
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Aim:To study the effect of MMP-9, TIMP-1 expressions on the brain edema around hematoma intracerebral hemorrhage(ICH). Methods:50 Wistar rats were randomly divided into control group, ICH group. The time (6 h, 24 h, 48 h, 72 h, 120 h) was established in these two groups. Brain water content and Evens blue (EB) content was determined and the expression of MMP-9, TIMP-1 was detected in the rat brain. Results:Brain water content, EB content and the expression of MMP-9, TIMP-1 arrived at the peak at the time 72h,48h and 48h respectively, the ultra-structure of blood-brain barrier(BBB) was damaged all the time. Conclusion:The expression of MMP-9 around hematoma can increase the penetrating ability of BBB, TIMP-1 can decrease the brain edema by inhibiting the expression of MMP-9.
Brain Edema
Cerebral edema
Intracerebral hematoma
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Objective To explore the neuroprotective effects of granulocyte colony-stimulating factor(G-CSF)in intracerebral hemorrhage(ICH)rats following the changes of brain edema and astrocytes plasticity in this study.Methods Sprague-Dawley rats were randomly divided into three groups:the sham operation group,the model group,the treating group.According to rat brain stereotaxic atlas,we made model of ICH by the method cutting off tail of rat to obtain blood.The treating group was administered rhG-CSF(60μg/kg)intraperitonealy 1h after operation.The brain edema was measured by dry-wet weigh method,MMP-9 and GFAP were measured by immunohistochemical method in every group post operation 6h、24h、48h、72h、7d、10d.Results The brain edema of the model group were markedly higher than the sham operation group(P0.05),reaching the peak at 48h、72h and the difference was significant inwith 6h、24h、7d、10d(P0.05).The brain edema of the treating group wasere significantly decreased than the model group(P0.05).The contents of MMP-9 protein were higher in the model group than in the sham operation group(P0.05).MMP-9 reached the peak at 48h and 72h in the model group,and there were significant difference compared to at 6h、24h、7d and 10d(P0.05).The contents of MMP-9 protein were significantly lower in the treating group than in the model group in each time point(P0.05).In the sham operation group,the changes of the contents of MMP-9 protein were negatively correlated with the brain edema(r=0.429,P0.05).In the model group,the changes of the contents of MMP-9 protein were positively correlated with the brain edema(r=0.922,P0.05).In the treating group,the changes of the contents of MMP-9 protein were positively correlated with the brain edema(r=0.844,P0.05).There was not GFAP-positive cell found in the sham operation group.In the model group,the GFAP was little expressed at 6h,increased at 48h,there were large numbers of GFAP-positive cells at 72h,reached a peak at 7d,then decreased at 10d.The expression of GFAP in the experimental group was identical to that of the model group at 6h;however,the number of GFAP-positive cells was obvious decreased than the model group at 24h、48h、72h、7d and 10d after intervention(P0.05).Conclusion G-CSF can downregulate MMP-9 expression to decrease the brain edema and inhibit the activation of astrocytes,which may be play an important role in the process of protection process inof the nerve tissues after intracerebral hemorrhage.
Brain Edema
Rat model
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Objective To clear the cerebral hemorrhage perifocal brain tissue at different time points of MMP-9 protein expression pattern the possible role of the occurrence and development of cerebral edema correlation and its clinical significance. Methods The cerebral hemorrhage foci were taken during the craniotomy operation for patients with cerebral hemorrhage at different time points. The patients were divided into 3 d groups according to the time of onset. To operative cranial path away from the hematoma at a little damage of brain tissue do as the samples in the control group by dry wet weighing method in measuring the brain water content,and immunohistochemical staining and RT-PCR methods observe changes of brain tissue around the MMP-9 expression in each group at different time points lesions. Results(1) The water content of brain tissue changeds,cerebral hemorrhage cerebral edema with bleeding time increased,in 6 h containing water hemorrhage increased significantly,after 24 h significantly increased,peaked in about three days,then reduced( P < 0. 05).(2) In the human brain hemorrhage perifocal MMP-9 shall have expression expressed,as compared with the control group,hemorrhage group were significant( P < 0. 05) compared to and bleeding between groups comparison showed a significant difference( P < 0. 05). The number of immune positive cells increased after bleeding 6 h,and the cell numbers of 24 h ~ 3 d cells was the most,then decreased gradually. MMP-9 was positively related to cerebral edema. Conclusion (1) The expression of MMP-9 in the human brain was significantly higher which was closely related to cerebral edema.(2) Abnormal expression of MMP-9 plays an important role in cerebral edema after hypertensive intracerebral hemorrhage and promotes the occurrence of cerebral edema and provides a new target for the treatment of cerebral hemorrhage.
Cerebral edema
Brain Edema
Brain tissue
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Objective To study the temporal profile of MMP-9 after spontaneous intracerebral hemorrhage and the relationship to the perihematomal edema volume(PHE) and clinical outcome.Methods MMP-9 was determined by enzyme-linked immunosorbent assays(ELISA) in 30 patients with intracerebral hemorrhage.C-reactive protein was determined by immunoturbidimetry.The relationship between the MMP-9 and the perihematomal edema volume according to cranial CT scan and neurological assessment was investigated.Results The serum level of MMP-9 was increased at 24 hours,the highest level of MMP-9 was found at 3 days,and after 7days MMP-9 level was decreased dramatically.MMP-9 level at 24 hours was positively correlated with PHE and the(disease.) Conclusion Serum MMP-9 level increased after deep intracerebral hemorrhage may be the index of predicting the severity of PHE and clinical outcome.
Spontaneous intracerebral hemorrhage
Brain Edema
Cerebral edema
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Objective To observe the expressions of matrix metalloproteinase-9 mRNA and the change of cerebral edema after diffuse brain injury in rats and discuss their correlation.Methods Marmaruu's diffuse brain injury model of rat was made.Real-time quantitative RT-PCR,dry-wet meth- od,histological techniques and electron microscope were used to determine the expressions of MMP-9 containing water in brain tissue and inflammatory reaction and uhrastructural changes of blood capillary at different time phases after truama.Results The expressions of MMP-9 mRNA started to increase at 1 hour,peaked at 12 hours(P0.01)and the increased MMP-9 mRNA level continued for one week in the traumatic group compared to the sham-operated group.At day 14,the MMP-9 mRNA levels declined to the level of the sham-operated group.The water content of brain tissues after diffuse brain injury was apparently higher in the traumatic group than in the sham-operated group,and inflammatory reaction was severe and the uhrastructures of blood capillary were disorganized in the traumatic group.Conclusion The expressions of MMP-9 mRNA are induced to increase after diffuse brain injury in rats.These finding suggests strongly that MMP-9 is involved in the cerebral edema of vascular origin,leading to aggravation of brain injury.
Brain Edema
Cerebral edema
Brain tissue
Matrix metalloproteinase 9
Blood capillary
Diffuse axonal injury
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Objective To study expression of MMP-9 and MMP-2 in rats brain after injection thrombin. Methods Wistar rats were divided randomly into 2 groups,sham-operated group and experiment group. The animals of experiment group were injected thrombin in brain. At the due time some rats were killed and brain tissue was removed to measure the water content by dry-wet weight method. The others were immunohistochemically stained to measure of the expression of MMP-9 and MMP-2.The animals of sham-operated group were injected normal saline. Results The water content of brain increased at 6h after injection thrombin,and peaked at 3d. Compared with sham-operated group,in experiment group the expression of MMP-9 positive cells were observed at 6h after injection thrombin (P 0.01 ),and peaked at 3d,then decreased gradually. The number of MMP-9 positive micro-blood vessel had the same change tendency as the positive cells. A few of MMP-2 positive cells were observed until 1d in experiment group,and peaked at 5 days,then decreased gradually. The increasing tendency lasted to 14d. The number of positive cells at 14d was significantly more than sham group (P 0.01 ). This tendency was similar to the number of MMP-2 positive micro-blood vessel. Conclusion Thrombin plays an important role in intracerebral hemorrhage on cerebral edema and tissue impairment. MMP-9 and MMP-2 contribute to brain edema and inflammatory reaction in the acute phase of ICH,and MMP-2 is perhaps important in rehabilitation of the brain injury.
Brain Edema
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