基质金属蛋白酶-9在脑缺血中的作用

基质金属蛋白酶-9（MMP-9）是参与细胞外基质降解的重要酶类。研究证实，脑缺血时MMP-9能分解细胞外基质和基底膜，破坏血脑屏障，最终导致神经元凋亡。其表达与脑缺血后血管源性脑水肿的发生、溶栓治疗后的出血性转化、脑白质降解等关系密切，在脑缺血后继发性损伤方面具有重要作用。     

白藜芦醇通过核因子-κB信号通路抑制脑缺血基质金属蛋白酶功能上调

目的 揭示白藜芦醇抑制脑缺血基质金属蛋白酶(MMP)-9功能上调的分子机制及其与核因子(NF)-κB信号通路联系.方法 建立大鼠四动脉前脑缺血模型,采用免疫印迹技术观察缺血后再灌海马脑区MMP-9蛋白水平和NF-κB核易位的变化;给予自由基清除剂白藜芦醇或NF-κB抑制剂吡咯二硫氨基甲酸酯(DTC),识别NF-κB信号通路是否参与了白藜芦醇对脑缺血MMP-9蛋白表达的调控.结果 脑缺血/再灌诱导海马脑区MMP-9蛋白水平和NF-κB核易位增加(P＜0.05).PDTC能一定程度的抑制缺血后MMP-9基因表达(P＜0.05).白藜芦醇能显著抑制脑缺血NF-κB核易位和MMP-9表达上调(P＜0.05).结论 脑缺血再灌,诱导MMP-9依赖NF-κB通路的蛋白水平增加,白藜芦醇能通过抑制NF-κB通路下调MMP-9的功能,继而阻断MMP-9激活介导的胞外基质降解及海马脑区损伤.     

早期应用辛伐他汀对急性冠状动脉综合征血清基质金属蛋白酶及其抑制因子和高敏C-反应蛋白水平的影响

目的:研究早期应用辛伐他汀对急性冠状动脉综合征患者稳定斑块、减少炎症反应的作用.方法:采用随机、对照方法,将137例急性冠状动脉综合征患者分为他汀治疗组(辛伐他汀20 mg/d,n=69)和他汀对照组(n=68);于发病12～48小时和治疗8周后分别测定血清基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制因子-1(TIMP-1)、MMP-9/TIMP-1、高敏C-反应蛋白(hs-CRP)水平.另设健康对照组(n=60)与之对照.结果:①治疗前他汀治疗组和他汀对照组的血清MMP-1、MMP-9、MMP-9/TIMP-1、TIMP-1、hs-CRP水平均较健康对照组明显增高(P＜0.01～0.001),与血脂水平不相关.②他汀治疗组经辛伐他汀治疗8周后血清MMP-1、MMP-9、MMP-9/TIMP-1、hs-CRP水平较治疗前均明显降低(P＜0.001),他汀对照组除血清hs-CRP水平降低外(P＜0.05),其他各项指标均无变化.结论:早期应用他汀治疗,可减少急性冠状动脉综合征患者的冠状动脉粥样斑块基质成分的降解和炎症反应,具有稳定斑块作用.     

急性脑梗死血清基质金属蛋白酶的表达及其意义

脑缺血可诱导基质金属蛋白酶 (MMPs:MMP-2 ,MMP- 9)的表达 ,通过促进细胞外基质 (ECM)降解和再灌注后血脑屏障开放 ,导致脑出血、脑水肿形成和白细胞浸润。组织基质金属蛋白酶抑制剂 - 1(TIMP- 1 )可抑制或拮抗 MMPs。本研究检测急性脑梗死患者 1 2 0例血清 MMP- 2、MMP- 9和 TIMP- 1含量变化 ,探讨其与急性脑梗死的关系。1　资料与方法1 .1　一般资料　本组急性脑梗死患者 1 2 0例 ,男 76例 ,女 44例 ,年龄 43～ 84岁 ,平均 (5 6± 8.9)岁。诊断符合第 4次全国脑血管会议修定的标准 ,且经头颅CT或 MRI证实 ,病程在 3 0天以内…     

基质金属蛋白酶与缺血性脑血管病

基质金属蛋白酶(MMP),尤其是MMP-2和MMP-9,在急性缺血性脑血管病的发病机制中起着重要作用。研究表明,它们不但能够降解微血管基底膜和细胞外基质,参与神经系统炎症反应和急慢性神经变性疾病;而且在脑缺血的早期诊断、促进神经元分化和凋亡以及在rtPA溶栓治疗后的出血性并发症中都发挥重要作用。MMP抑制剂的应用已为缺血性脑血管病的治疗提供了一种新的选择。     

阿托伐他汀对急性脑梗死患者基质金属蛋白酶-9表达的干预作用

研究证明,基质金属蛋白酶-9(matrix metalloproteinase9,MMP-9)能降解胶原蛋白和弹性蛋白,它的炎症激活作用可能促进基质降解增加,体内和体外动脉粥样硬化斑块中MMP-9都能诱导胶原蛋白降解.     

健脾补土法对大鼠脑缺血再灌注后层黏连蛋白降解的影响

目的探讨健脾补土法对大鼠脑缺血再灌注后神经细胞周围层黏连蛋白(LN)的降解机制及其脑保护作用。方法 38只大鼠随机分为:假手术组8只,模型组10只,健脾补土传统汤剂组10只,健脾补土超微剂型组10只,大脑中动脉栓塞再通法建立脑缺血再灌注模型。进行神经功能症状评分,脑组织病理形态学观察,采用TUNEL法检测凋亡神经元,免疫组织化学法检测LN和基质金属蛋白酶9(MMP-9)阳性表达。结果与假手术组比较,模型组神经功能症状评分、细胞凋亡指数、MMP-9阳性细胞表达数明显升高,LN表达明显降低(P0.01)。与模型组比较,健脾补土传统汤剂组和健脾补土超微剂型组神经功能症状评分、细胞凋亡指数、MMP-9阳性细胞表达数明显降低,LN表达明显升高(P0.05,P0.01)。结论 LN降解在脑缺血再灌注损伤中起重要作用,健脾补土法可能通过抑制MMP-9和减少LN降解减轻缺血再灌注所致神经元损伤。     

阿司匹林对川崎病小鼠的治疗作用及其机制研究

目的:采用干酪乳杆菌细胞壁提取物(LCWE)诱导川崎病(KD)小鼠模型,探讨阿司匹林对KD小鼠的治疗作用及其可能的新的作用机制。方法:采用LCWE诱导KD小鼠模型,给予6.25~25.00mg/ml阿司匹林治疗10d,观察小鼠实验期间的一般情况和冠状动脉(冠脉)病变情况,以及测定小鼠血清中肿瘤坏死因子α(TNF-α)、前列腺素E2(PGE2)、基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶组织抑制因子-1(TIMP-1)含量,并计算MMP-9/TIMP-1比值。结果:小鼠单次腹腔注射LCWE后,在前3d内,KD小鼠进食、饮水、活动量明显减少;给阿司匹林治疗10d后,与正常对照组比较,KD小鼠冠脉周围有大量炎细胞浸润,血清中TNF-α和PGE2含量显著升高(P0.01),同时伴有MMP-9、TIMP-1以及MMP-9/TIMP-1比值的明显升高(P0.05),而阿司匹林组小鼠则冠脉周围炎性细胞明显减少,还能不同程度降低血清中TNF-α、PGE2、MMP-9的含量,以及降低MMP-9/TIMP-1比值(P0.05或P0.01)。结论:阿司匹林对KD引起的冠脉损伤有一定的疗效,可能与降低KD小鼠血清中的炎性因子TNF-α和PGE2的含量,以及降低与细胞外基质降解密切相关的MMP-9含量和MMP-9/TIMP-1比值有关。     

脑缺血预处理对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9表达的影响

目的 探讨脑缺血预处理(ischemic preconditioning,IP)对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的影响.方法 154只Wistar大鼠随机分为假手术组(14只)、非缺血预处理(non-ischemic preconditioning,NIP)组(70只)和IP组(70只),后两组再随机分为5个亚组,每组14只.线栓法建立大脑中动脉闭塞模型,缺血预处理10 min,分别在IP后1、3、7、14和21 d进行再次缺血2 h再灌注22 h.采用2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色测定脑梗死体积,通过测定渗出血管外的伊文思蓝(Evans blue,EB)含量评价血脑屏障通透性,采用于湿重法评价脑水肿程度,免疫组化染色和原位杂交法检测MMP-9蛋白和mRNA表达.结果 与NIP组相应亚组比较,IP组缺血预处理1、3和7 d亚组神经功能缺损评分显著降低,脑梗死体积显著缩小,EB含量和脑水含量显著降低,MMP-9蛋白和mRNA表达均显著下调(P＜0.05或P＜0.01).IP组1、3和7 d亚组梗死体积和MMP-9 mRNA表达较IP组14 d和21 d亚组显著缩小或下调,3 d和7 d亚组EB含量、脑水含量和MMP-9蛋白表达较其他亚组显著降低,其中以3 d亚组降低最显著(P＜0.05).结论 缺血预处理诱导的血脑屏障通透性改变和MMP-9表达下调在脑缺血耐受中发挥着重要作用.     

尿激酶溶栓对大脑中动脉血栓栓塞模型大鼠MMP-9、血脑屏障通透性和脑出血的影响

目的 观察栓塞性脑缺血后及应用尿激酶(urokinase,UK)溶栓后基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达及对脑出血量和血脑屏障通透性的影响,探讨MMP-9与血脑屏障通透性和溶栓后脑出血之间的关系.方法 通过颈动脉内注射自体血制作大鼠血栓栓塞性大脑中动脉闭摩模型,缺血6h后静脉应用UK,24 h后分别采用免疫组化法检测脑组织MMP-9表达、伊文思蓝渗出法检测血脑屏障通透性、TTC染色法检测脑梗死体积、分光光度法检测脑出血量.结果 脑缺血组MMP-9表达显著高于假手术组(P＜0.01),UK溶栓组显著高于脑缺血组(P＜0.01).脑缺血组伊文思蓝含量为(5774.00±1659.70)ng/g,显著高于假手术组的(643.33±151.34)ng/g(P＜0.01),UK溶柃组为(6283.83±1099.28)ng/g,有高于脑缺血组的趋势.UK溶柃组和脑缺血组脑出血量分别为(3.16±8.84)μl(中位数±四分位数)和(0.00±1.48)μl,脑出血发生率分别为25.00%和4.17%.结论 UK溶栓可能上调 MMP-9表达,MMP-9表达与BBB通透性增加与溶栓后脑出血有关.     

脑心通胶囊对大鼠局灶性脑缺血再灌注损伤及MMP-2、MMP-9表达的影响

目的观察脑心通胶囊对大鼠局灶性脑缺血再灌注脑组织病理变化及MMP-2、MMP-9表达的影响，并探讨其可能的保护机制。方法建立大鼠大脑中动脉缺血再灌注模型，应用HE及S-P免疫组化法分别观察模型组及用药组大鼠全脑组织的病理改变及MMP-2、MMP-9表达的变化。结果假手术组大鼠脑组织形态结构正常，MMP-2、MMP-9见少量散在阳性表达或不表达；模型组大鼠大脑缺血再灌注区组织明显水肿、蜕变、坏死伴少量炎细胞浸润，对大脑相应区及双侧小脑轻度水肿，MMP-2、MMP-9表达较假手术组对应区显著升高（P〈0．01或P〈0．05），其中缺血侧大脑以坏死区边缘脑组织表达为甚，且较对侧大脑及双侧小脑明显升高（P〈0．05）；脑心通用药组大鼠大脑缺血区组织水肿、蜕变、坏死较模型组明显减轻，对侧大脑相应区及双侧小脑脑组织形态结构正常，MMP-2、MMP-9表达较模型组对应区显著降低（P〈0．05）。结论脑心通胶囊对大鼠局灶性脑缺血再灌注后包括病灶在内的全脑损伤有保护作用，其作用机制可能与降低MMP-2、MMP-9表达有关。     

缺血性脑卒中血浆MMP-9的测定及临床意义

目的　观察脑梗死患者血浆基质金属蛋白酶 -9(MMP-9)的含量变化 ,探讨其在脑梗死发生发展过程中的作用和意义。方法　用 ELISA法检测 3 7例脑梗死患者发病 2～ 5天和 2周 ,以及 3 0例健康体检者血浆 MMP-9的含量。结果　脑梗死发病 2～ 5天的血浆 MMP-9水平显著高于发病 2周 (P<0 .0 1 )和对照组 (P<0 .0 1 )。后两者比较无显著差异 (P>0 .0 5 )。梗塞灶面积大小与脑梗死发病 2～ 5天血浆 MMP-9水平呈正相关 (r=0 .75 7,P<0 .0 1 )。结论　 MMP-9水平可以反映脑梗塞灶面积大小。     

Inhibition of matrix metalloproteinase-9 activity by trandolapril after middle cerebral artery occlusion in rats.

We investigated whether an angiotensin-converting enzyme (ACE) inhibitor could inhibit matrix metalloproteinase (MMP) activities in cerebral infarct lesions after middle cerebral artery occlusion (MCAO) in rats. After placebo or trandolapril (5 mg/kg per day) was administered orally for 7 days, we permanently occluded the right middle cerebral artery. ACE activity in extracts from the infarct side of placebo-treated rats was significantly higher than that in extracts from the non-infarct side from 5 days after MCAO, though they did not differ at 1 day. ACE activities in extracts from both hemispheric segments in the trandolapril-treated group were significantly decreased compared with those in the placebo-treated group before MCAO, and this significant reduction persisted even at 7 days after MCAO. In the placebo-treated group, MMP-9 and MMP-2 activities in the infarct side were significantly increased at 12 h and at 1 day after MCAO, respectively. Trandolapril treatment significantly reduced MMP-9 and MMP-2 activities to 68.5% and 53.2%, respectively. Seven days after MCAO, the ratios of infarct areas to the hemispheric sectional areas in placebo- and trandolapril-treated rats were 55.4+/-2.1% and 30.9+/-2.9%, respectively, and this difference was significant. Neurological severity scores were significantly improved from 1 to 7 days after MCAO in trandolapril-treated rats. Cumulative survival in trandolapril-treated rats was significantly increased compared with that in placebo-treated rats. Thus, the inhibition of MMP-9 by trandolapril might be part of the mechanism that prevents cerebral damage after cerebral ischemia.     

胡黄连苷Ⅱ在大鼠脑缺血损伤中治疗剂量和时间窗的优化

目的探讨胡黄连苷Ⅱ治疗大鼠脑缺血损伤的最佳治疗剂量和时间窗。方法应用双侧颈总动脉结扎法建立大鼠脑缺血模型,将48只大鼠模型,按二因素四水平[L16(45)]正交试验设计分组。治疗时间窗设定缺血1.0、1.5、2.0、2.5 h,共4个水平,治疗剂量设定5、10、20、40 mg/kg共4个水平。按照设定剂量经腹腔注射胡黄连苷Ⅱ干预治疗,采用酶联免疫吸附法(ELISA)检测血清和脑组织水通道蛋白4(AQP-4)、基质金属蛋白酶9(MMP-9)和环氧合酶2(COX-2)的水平,评价胡黄连苷Ⅱ治疗大鼠脑缺血损伤的疗效。结果①根据血清和脑组织AQP-4水平分析结果,胡黄连苷Ⅱ治疗脑缺血损伤的最佳治疗时间窗和剂量分别为脑缺血2.0 h,腹腔注射20 mg/kg;脑缺血1.5 h,腹腔注射20 mg/kg。②根据血清和脑组织MMP-9水平分析结果,最佳治疗时间窗和剂量分别为脑缺血1.5 h,腹腔注射20 mg/kg;脑缺血2.0 h,腹腔注射20 mg/kg。③根据血清和脑组织COX-2水平分析结果,最佳治疗时间窗和剂量分别为脑缺血1.5 h,腹腔注射10 mg/kg;脑缺血1.5 h,腹腔注射20 mg/kg。结论根据用药剂量最小化和治疗时间窗最大化的原则综合评价,根据AQP-4、MMP-9、COX-2测定结果,胡黄连苷Ⅱ治疗脑缺血损伤的最佳治疗时间窗和剂量为脑缺血1.5～2.0 h,腹腔注射剂量10～20 mg/kg。     

Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats

We have previously shown that melatonin reduces postischemic rises in the blood-brain barrier (BBB) permeability and improves neurovascular dysfunction and hemorrhagic transformation following ischemic stroke. It is known that activation of the matrix metalloproteinases (MMPs) plays a crucial role in the pathogenesis of brain edema and hemorrhagic transformation after ischemic stroke. We, herein, investigated whether melatonin would ameliorate MMP-2 and MMP-9 activation and expression in a rat model of transient focal cerebral ischemia. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery (MCA) occlusion using an intraluminal filament. Melatonin (5 mg/kg) or vehicle was intravenously injected upon reperfusion. Brain infarction and hemorrhage within infarcts were measured, and neurological deficits were scored. The activity and expression of MMP-2 and MMP-9 were determined by zymography, in situ zymography and Western immunoblot analysis. Cerebral ischemia-reperfusion induced increased pro-MMP-9 and MMP-9 activity and expression 24 hr after reperfusion onset. Relative to controls, melatonin-treated animals, however, had significantly reduced levels in the MMP-9 activity and expression (P < 0.01), in addition to reduced brain infarct volume and hemorrhagic transformation as well as improved sensorimotor neurobehavioral outcomes. No significant change in MMP-2 activity was observed throughout the course experiments. Our results indicate that the melatonin-mediated reductions in ischemic brain damage and reperfusion-induced hemorrhage are partly attributed to its ability to reduce postischemic MMP-9 activation and increased expression, and further support the fact that melatonin is a suitable as an add-on to thrombolytic therapy for ischemic stroke patients.     

Expression and significance of angiostatin,vascular endothelial growth factor and matrix metalloproteinase-9 in brain tissue of diabetic rats with ischemia reperfusion

Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in the brain tissue. Results: The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group(P0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group(P0.05). MMP-9 began to be be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group(P0.05). Conclusions: The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus.     

胸腺素β4对大鼠局灶性脑缺血再灌注损伤后血脑屏障的影响

目的：观察胸腺素β4对大鼠局灶性脑缺血再灌注损伤后血脑屏障的影响,并探讨其作用机制。方法将72只SD大鼠随机分为假手术组、对照组、胸腺素β4组各24只。采用线栓法制作大鼠大脑中动脉闭塞局灶性脑缺血再灌注模型,再灌注24 h后,采用干湿重法测定缺血脑组织含水量,通过检测伊文蓝渗透到缺血侧脑组织的含量观察血脑屏障的通透性,应用RT-PCR法检测缺血脑组织紧密连接蛋白5（ Claudin-5）和基质金属蛋白酶-9（MMP-9） mRNA表达。结果脑缺血再灌注损伤24 h后,与假手术组比较,对照组缺血侧脑含水量、伊文蓝含量、MMP-9 mRNA表达明显增加,Claudin-5 mRNA表达显著减少（ P均＜0．01）;与对照组比较,胸腺素β4组缺血侧脑组织含水量、缺血侧伊文蓝含量、MMP-9 mRNA明显降低,Claudin-5 mRNA表达明显升高（P均＜0．01）。结论胸腺素β4对大鼠脑缺血再灌注损伤后的血脑屏障具有保护作用,其作用机制可能是通过促进Claudin-5 mRNA表达和抑制MMP-9 mRNA表达实现的。     

大鼠脑梗死早期活性MMP-9表达的实验研究

目的　探讨 SD大鼠脑梗死早期活性 MMP-9的时间表达过程。方法　线栓法建立 SD大鼠永久性大脑中动脉闭塞 (MCAO)模型 ,各经 2 h、6h和 1 6h血管闭塞后 ELISA法测定各时间点组脑组织匀浆中活性 MMP-9的水平 ,假手术组作为阴性对照。结果　经过 2 h、6h和 1 6h血管闭塞后 ,梗死侧脑组织中活性 MMP-9水平各为 6.3 6±1 .40 u/ mg,8.73 h± 3 .3 3 u/ mg和 1 4.68± 2 .5 9u/ mg,其中 1 6h组各为 6h、2 h组的 1 .9和 2 .2倍 (P<0 .0 5 ) ;三时点水平与同时点假手术组相比 ,6h(P<0 .0 5 )和 1 6h组具有统计学差异 (P<0 .0 1 )。结论　脑梗死早期可以诱导 MMP-9基因表达 ,其组织中活性成份于血管闭塞后 6小时开始增高 ,1 6小时明显升高 ,提示 MMP-9可能参与脑梗死后组织损伤的早期病理过程。     

Hyperbaric Oxygen Effect on MMP-9 After a Vascular Insult

Matrix metalloproteinease-9 (MMP-9) is involved in a host of processes. Many of its processes are physiologically beneficial as well as detrimental. The over-expression of this enzyme has been implicated as a contributory factor to some of the sequalae associated with cerebral ischemia, cell death, non-healing wounds, traumatic brain injury, aneurysms, and plaque instability in atherosclerosis. Several studies have examined the effect of hyperbaric oxygen (HBO) on MMP-9 expression. Because this proteinase is involved in both chronic and acute pathology, we wanted to investigate an acute expression model and see if, and how quickly, its expression would respond to HBO therapy. Our patient was scheduled to have elective surgery with an overnight stay followed by a series of HBO exposures. The patient served as her own control. An MMP-9 and urine pH was obtained prior to surgery to establish a baseline. On days 1, 3, and 4 post-op, samples were obtained before and after hyperbaric exposure. The patient was exposed to 100% O2 at 2.5 ATA for 60 min during each treatment for 5 days. The patient’s MMP-9 values were dramatically elevated after surgery as compared to the baseline readings. The percentage increase from baseline was 400%. Our patient showed a significant reduction in MMP-9 expression after each hyperbaric exposure with the greatest decrease seen on post-op day 1 and subsequent exposures showing slightly less expression. Reduction in MMP-9 expression ranged from 46% on day 1 to 30% on post-op day 4. This case study suggests that if done relatively soon after a vascular or tissue insult, HBO can reduce MMP-9 expression. Chronic vascular pathologies, such as atherosclerotic plaque and aneurysms where over-expression of MMP-9 may result in acute coronary syndrome (ACS) or cerebral vascular accidents (CVAs), may be mitigated by a series of HBO treatments that reduce MMP-9 expression. Causality and/or contributory effects of MMP-9 expression in both pathologic and physiologic processes needs to be further elucidated. The understanding of how HBO therapy modulates these may provide an additional insight into mechanisms and future potential therapies for pathologic conditions such as those described above.