Activation of P2X4 receptor exacerbates acute brain injury after intracerebral hemorrhage

IntroductionIntracerebral hemorrhage (ICH) accounts for 10%–15% of all strokes and culminates in high mortality and disability. After ICH, brain injury is initiated by the mass effect of hematoma, followed by secondary cytotoxic injury from dying brain cells, hematoma disintegration, and cascading brain immune response. However, the molecular mechanism of secondary cytotoxic brain injury in ICH is not completely understood. The sensitive purinergic receptor, P2X4 receptor (P2X4R), was known to recognize extracellular free ATP released by dying cells during tissue injury.AimsIn this study, we aim to understand the role of P2X4R in acute brain injury triggered by ICH.ResultsIn this study, we found that the sensitive purinergic receptor, P2X4R, was upregulated in the brain of patients with ICH as well as in a mouse model of ICH induced by collagenase injection. P2X4R blockage with the specific inhibitor 5‐BDBD attenuated brain injury in ICH mice by significantly reducing brain edema, blood–brain barrier leakage, neural death, and ultimately acute neurodeficits. Further study indicated that the protective effect of P2X4R inhibition is related to decreased pro‐inflammatory activity of microglia and recruitment of peripheral immune cells into the hemorrhagic brain.ConclusionsThese results suggest that the P2X4 receptor is activated by ICH stimuli which worsen brain injury following ICH.     

Acute hyperglycemia together with hematoma of high-glucose blood exacerbates neurological injury in a rat model of intracerebral hemorrhage

Recent evidence suggests that admission hyperglycemia has deleterious effects on the survival and functional outcome of patients with intracerebral hemorrhage (ICH). In this study, we first induced acute hyperglycemia in male adult Sprague-Dawley rats by intraperitoneal injection of 50% glucose (6 mL/kg), and created the ICH model thereafter by delivering autologous whole blood or homologous normalglucose blood into the right basal ganglia. Twentyfour hours later, we assessed the neurological injury, evaluated the hematoma and brain water content, and investigated autophagy. We found elevations of neurological deficit scores, brain water content, and microtubule-associated protein light chain-3 (LC3) and beclin-1 protein levels, and decreased SQSTM1/ p62 levels after ICH with normal-glucose blood (without hyperglycemia). Acute hyperglycemia with ICH of high-glucose blood hematoma was associated with significantly increased forelimb-use asymmetry test scores, brain water content and SQSTM1/p62 protein levels, and evident decreases in the ratio of LC3-II/LC3-I and beclin-1 protein levels. On the other hand, acute hyperglycemia and ICH with normalglucose blood hematoma only slightly increased the neurological deficit scores and brain water content (P >0.05). In conclusion, the autophagy pathway was activated after ICH, and acute hyperglycemia with hematoma of high-glucose blood exacerbates the neurological injury, and reduces autophagy around the hematoma.     

Analysis of thrombin‐antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage patients after clot removal

Background and purpose: Animal experiments indicate that the cerebral thrombin is associated with secondary brain damage after intracerebral hemorrhage (ICH). This study was aimed to investigate the concentrations of thrombin‐antithrombin complex (TAT) in hematoma fluid and plasma of the patients with ICH after surgery and analyze the correlation between TAT complex levels and severity of ICH. Methods: Sixty patients with ICH were enrolled. Craniotomy for removal of intracranial blood clot was performed within 24 h after ICH. Hematoma fluid and plasma were collected on postoperative days 1, 2, and 4. The plasma obtained from healthy subjects and cerebrospinal fluid from patients without cerebrovascular diseases served as controls, respectively. Enzyme‐linked immunosorbent assay was used to determine the concentrations of TAT complex in the patients and controls. Results: TAT complex concentrations in both postoperative plasma and hematoma fluid of patients with ICH were significantly higher than those of the controls (P < 0.01). In patients with ICH, hematoma fluid had a higher TAT complex level than plasma (P < 0.01). The preoperative hemorrhage volume and postoperative TAT complex levels in plasma and hematoma fluid correlated positively with National Institutes of Health stroke scale and negatively with Glasgow coma score (P < 0.01). Conclusion: This study indicates that TAT complex levels of plasma and hematoma fluid correlate positively with the severity of ICH. Determination of the plasma TAT complex concentration is helpful for the evaluation of the severity of post‐ICH brain injury.     

Potential Application of Intranasal Insulin Delivery for Treatment of Intracerebral Hemorrhage: A Review of The Literature

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke associated with high morbidity and mortality that is considered a medical emergency, mainly managed with adequate blood pressure control and creating a favorable hemostatic condition. However, to date, none of the randomized clinical trials have led to an effective treatment for ICH. It is vital to better understand the mechanisms underlying brain injury to effectively decrease ICH-associated morbidity and mortality. It is well known that initial hematoma formation and its expansion have detrimental consequences. The literature has recently focused on other pathological processes, including oxidative stress, neuroinflammation, blood-brain barrier disruption, edema formation, and neurotoxicity, that constitute secondary brain injury. Since conventional management has failed to improve clinical outcomes significantly, various neuroprotective therapies are tested in preclinical and clinical settings. Unlike intravenous administration, intranasal insulin can reach a higher concentration in the cerebrospinal fluid without causing systemic side effects. Intranasal insulin delivery has been introduced as a novel neuroprotective agent for certain neurological diseases, including ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Since there is an overlap of mechanisms causing neuroinflammation in these neurological diseases and ICH, we believe that preclinical studies testing the role of intranasal insulin therapy in ICH are warranted.     

Nimodipine treatment to assess a modified mouse model of intracerebral hemorrhage

One of the main limitations of intracerebral hemorrhage (ICH) research is lack of reproducible animal models. ICH appears to be associated with a volume of edema and ischemic injury surrounding the hematoma that may be reduced by nimodipine due to its vasodilating and cytoprotective effects. The present study was designed to produce a modified ICH model in mice based on the double-injection method initially developed by Dr. Belayev and accordingly performed in 3 groups: to evaluate this model itself and to assess the pharmacological effects of nimodipine in this model, respectively. In 80 ICR mice (32 +/- 3 g), ICH was induced by 30 microL whole blood injection into the caudate nucleus. ICH animals were then randomly received either nimodipine (5 mg/kg) or vehicle intraperitoneal injection just before and every 24 h after ICH (total of four times). The changes for cortical blood flow (CBF) were studied by the technique of Laser Doppler Perfusion Measure (LDPM). Animals were rated on a behavioral test and sacrificed at 72 h after ICH. The brains were removed, and hematoma volume and brain edema were subsequently determined. Due to the vasodilating effect of nimodipine, ICH animals treated with nimodipine had marked improved CBF accompanied by the improvement of forelimb placing performance compared with vehicle-treated ICH animals, though there was no marked difference in the hematoma volume and brain water content. In conclusion, the 30 microL whole blood injection closely mimicked natural ischemic events that occurred in human massive ICH and confirmed the anti-ischemia effect of nimodipine. This study suggested that nimodipine could be markedly effective to reduce edema and hematoma volume when administered in combination with other neuroprotective agents because ICH can induce brain injury by multiple mechanisms.     

家犬实验陛脑出血后血肿周围脑代谢的微透析监测

目的研究脑出血（intracerebral hemorrhage,ICH）后继发脑损伤的机制。方法雄性成年家犬12只,随机分为ICH组（n=6）和生理盐水对照组（n=6）,ICH组于额叶注入非抗凝自体动脉血,对照组动物在相同部位注入等量生理盐水。在模型制备后2h、6h、24h、3d、7d、14d进行血肿周围脑组织间液微透析,监测葡萄糖、乳酸、丙酮酸、甘油和谷氨酸浓度。结果ICH组葡萄糖浓度无显著变化;乳酸浓度在注血后24h和3d升高;丙酮酸浓度在注血后6h、24h和3d升高;甘油浓度在注血后24h升高：谷氨酸浓度在注血后升高,3d达到高峰,至14d明显高于对照组和基础值。结论ICH后血肿周围脑组织代谢变化提示存在“生化半暗带”区域,兴奋性氨基酸的聚集可能是加重和维持继发性脑损伤的重要因素。     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

大鼠脑出血后血肿周围凝血酶与脑细胞凋亡和脑水肿的关系

目的 研究大鼠脑出血后血肿周围脑组织中凝血酶的变化及其与脑细胞凋亡和脑水肿的关系.方法 105只成年雄性SD大鼠随机均分为脑出血组、生理盐水组和正常对照组.每组再随机均分为7个时相,分别为6 h、12 h、24 h、48 h、3 d、5 d、7 d;用立体定向脑内注射法制备脑出血模型;用ELISA法检测脑组织中凝血酶-抗凝血酶复合物的含量;用流式细胞仪检测脑细胞的凋亡率;用干-湿重法检测脑组织的含水量;用透射电镜观察脑组织的形态学变化.结果 制备动物模型后,脑出血组各时相血肿周围脑组织中凝血酶含量、脑细胞凋亡率、脑组织含水量均明显高于生理盐水组和正常对照组;血肿周围脑组织中凝血酶-抗凝血酶复合物的含量与脑细胞凋亡率和脑组织含水量之间均呈正相关;电镜下,在脑出血组各时相脑组织切片中均可见大量的脑细胞凋亡和毛细血管周围大片组织间隙水肿,以及神经纤维脱髓鞘改变.结论 脑出血后,血肿周围脑组织中凝血酶含量明显升高,可导致脑细胞凋亡和脑水肿,凝血酶的含量与脑细胞凋亡率和脑组织含水量呈正相关;尽早清除血肿有望改善凝血酶引起的继发性脑损伤.     

Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages

OBJECTIVE: Phagocytosis is necessary to eliminate the hematoma after intracerebral hemorrhage (ICH); however, release of proinflammatory mediators and free radicals during phagocyte activation is toxic to neighboring cells, leading to secondary brain injury. Promotion of phagocytosis in a timely and efficient manner may limit the toxic effects of persistent blood products on surrounding tissue and may be important for recovery after ICH. METHODS: Intrastriatal blood injection in rodents and primary microglia in culture exposed to red blood cells were used to model ICH and to study mechanisms of hematoma resolution and phagocytosis regulation by peroxisome proliferator-activated receptor gamma (PPARgamma) in microglia/macrophages. RESULTS: Our study demonstrated that the PPARgamma agonist, rosiglitazone, promoted hematoma resolution, decreased neuronal damage, and improved functional recovery in a mouse ICH model. Microglia isolated from murine brains showed more efficient phagocytosis in response to PPARgamma activators. PPARgamma activators significantly increased PPARgamma-regulated gene (catalase and CD36) expression, whereas reducing proinflammatory gene (tumor necrosis factor-alpha, interleukin-1beta, matrix metalloproteinase-9, and inducible nitric oxide synthase) expression, extracellular H(2)O(2) level, and neuronal damage. Phagocytosis by microglia was significantly inhibited by PPARgamma gene knockdown or neutralizing anti-CD36 antibody, whereas it was enhanced by exogenous catalase. INTERPRETATION: PPARgamma in macrophages acts as an important factor in promoting hematoma absorption and protecting other brain cells from ICH-induced damage.     

Involvement of thrombin and mitogen-activated protein kinase pathways in hemorrhagic brain injury

Thrombin is thought to play an important role in brain damage associated with intracerebral hemorrhage (ICH). We previously showed that activation of mitogen-activated protein (MAP) kinases and recruitment of microglia are crucial for thrombin-induced shrinkage of the striatal tissue in vitro and thrombin-induced striatal damage in vivo. Here we investigated whether the same mechanisms are involved in ICH-induced brain injury. A substantial loss of neurons was observed in the center and the peripheral region of hematoma at 3 days after ICH induced by intrastriatal injection of collagenase in adult rats. Intracerebroventricular injection of argatroban or cycloheximide, both of which prevent thrombin cytotoxicity in vitro, exhibited a significant neuroprotective effect against ICH-induced injury. ICH-induced neuron loss was also prevented by a MAP kinase kinase inhibitor (PD98059) and a c-Jun N-terminal kinase inhibitor (SP600125). These drugs had no effect on hematoma size or ICH-induced brain edema. Activation of extracellular signal-regulated kinase in response to ICH was observed in both neurons and microglia. Despite their neuroprotective effects, MAP kinase inhibitors did not decrease the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells appearing after ICH. Identification of cell types revealed that TUNEL staining occurred prominently in neurons but not in microglia, whereas inhibition of MAP kinases resulted in appearance of TUNEL staining in microglia. These results suggest that thrombin and the activation of MAP kinases are involved in ICH-induced neuronal injury, and that neuroprotective effects of MAP kinases are in part mediated by arrestment of microglial activities.     

Glial responses, neuron death and lesion resolution after intracerebral hemorrhage in young vs. aged rats

Intracerebral hemorrhage (ICH) usually affects older humans but almost no experimental studies have assessed aged animals. We address how aging alters inflammation, neuron death and lesion resolution after a hemorrhage in the rat striatum. In the normal aged brain, microglia displayed a 'dystrophic' phenotype, with shorter cellular processes and large gaps between adjacent cells, and there was more astrocyte reactivity. The ICH injury was monitored as hematoma volume and number of dying neurons at 1 and 3 days, and the volume of the residual lesion, ventricles and lost tissue at 28 days. Inflammation at 1 and 3 days was assessed from densities of microglia with resting vs. activated morphologies, or expressing the lysosomal marker ED1. Despite an initial delay in neuron death in aged animals, by 28 days, there was no difference in neuron density or volume of tissue lost. However, lesion resolution was impaired in aged animals and there was less compensatory ventricular expansion. At 1 day after ICH, there were fewer activated microglia/macrophages in the aged brain, but by 3 days there were more of these cells at the edge of the hematoma and in the surrounding parenchyma. In both age groups a glial limitans had developed by 3 days, but astrocyte reactivity and the spread of activated microglia/macrophages into the surrounding parenchyma was greater in the aged. These findings have important implications for efforts to reduce secondary injury after ICH and to develop anti-inflammatory therapies to treat ICH in aged humans.     

水通道蛋白4与脑出血后脑水肿形成的关系研究

目的：研究水通道蛋白4（AQP4）在脑出血后脑水肿形成中的作用。方法：以AQP4基因敲除（AQP4^-/-）小鼠为研究对象,分别在AQP4^＋/＋和野生型（AQP4^-/-）小鼠右侧基底节区立体定向注入5μL自体全血建立脑出血模型。比较两组小鼠脑出血后神经功能缺损、脑含水量、血肿周围组织脑比重、伊文思蓝漏出量及脑组织毛细血管超微结构间的差异。结果：脑出血后AQP4^＋/＋小鼠脑内AQP4蛋白表达量显著增高。AQP4基因的缺失加剧了脑出血神经功能缺损及患侧大脑半球的含水量,降低了血肿周围组织的脑比重,加剧了伊文思蓝的渗漏及毛细血管超微结构的损坏。结论：AQP4基因缺失加剧了脑出血损伤,包括水肿形成、血脑屏障破坏。对脑出血后AQP4表达增高的保护性机制研究可能会为临床治疗脑出血后脑水肿提供新的靶点及思路。     

Mast cell blocking reduces brain edema and hematoma volume and improves outcome after experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is associated with high mortality and disability, and there is no widely approved clinical therapy. Poor outcome after ICH results mostly from a mass effect owing to enlargement of the hematoma and brain swelling, leading to displacement and disruption of brain structures. Cerebral mast cells (MC) are resident inflammatory cells that are located perivascularly and contain potent vasoactive, proteolytic, and fibrinolytic substances. We previously found pharmacological MC stabilization and genetic MC deficiency to be associated with up to 50% reduction of postischemic brain swelling in rats. Here, we studied the role of MC and MC stabilization in ICH using in vivo magnetic resonance imaging and ex vivo digital imaging for calculating brain edema and hematoma volume. In a rat ICH model of autologous blood injection into the basal ganglia, four groups of Wistar rats received either saline or sodium cromoglycate (MC stabilizer, two groups) or compound 48/80 (MC degranulator). Evaluated 24 h later, MC stabilization had resulted in highly significantly better neurologic scores (P<0.001), decrease mortality (P=0.002), less brain swelling (P<0.001), and smaller hematoma volume growth (P<0.001) compared with saline and compound 48/80. Moreover, to support our hypothesis, we induced ICH in MC-deficient rats and their wild-type littermates (WT). MC-deficient rats responded with significantly better neurologic scores (P<0.001), decrease mortality (0% versus 25%), less brain swelling (P<0.05), and smaller hematoma growth (P<0.05) than WT. The role of MC deserves a close evaluation as a potential target in the development of novel forms of ICH therapy.     

脑出血患者血肿周围组织神经元凋亡与Bcl-2、Bax蛋白表达关系的研究

目的探讨脑出血(ICH)患者血肿周围组织神经元凋亡与凋亡相关基因Bcl2、Bax蛋白表达的关系。方法采用缺口末端标记法、免疫组化法分别检测ICH患者血肿周围组织神经元凋亡率和Bcl2、Bax表达水平,分析神经元凋亡率与Bcl2、Bax表达及Bax/Bcl2值的关系;出血量与Bcl2、Bax表达及Bax/Bcl2值的关系,以及神经元凋亡率与出血量、病程、神经功能缺损程度评分(NDS)的关系。结果ICH患者血肿周围组织神经元凋亡率及Bcl2、Bax表达明显高于正常对照组(均P<0.01);血肿周围组织神经元凋亡率与Bcl2表达呈负相关(r=-0.682,P<0.01),与Bax、Bax/Bcl2值表达呈正相关(r=0.592、0.740,均P<0.01)。出血量与血肿周围组织Bcl2表达呈负相关(r=-0.677,P<0.01),与Bax表达及Bax/Bcl2值呈正相关(r=0.654、0.751,均P<0.01)。细胞凋亡率与出血量及NDS呈正相关(r=0.829、0.897,均P<0.01),与病程不相关。结论细胞凋亡机制参与了ICH后继发性神经元损伤;Bcl2、Bax蛋白及Bax/Bcl2值对凋亡具有调控作用。     

Validation of perihematomal edema expansion as a new imaging biomarker to predict clinical outcome in patients with intracerebral hemorrhage

ObjectivesThe use of hematoma expansion (HE) in intracerebral hemorrhage (ICH) patients is limited due to its low sensitivity. Perihematomal edema (PHE) has been considered an important marker of secondary brain injury after ICH. Enrolling PHE expansion to redefine traditional ICH expansion merits exploration.Materials and methodsThis study analyzed a cohort of patients with spontaneous ICH. The hematoma and PHE were manually segmented. Logistic regression analysis was utilized to identify risk factors for poor outcomes. Receiver operating characteristic curve analysis was performed to calculate the predictive values of PHE expansion and HE. Poor neurological outcome was defined as a modified Rankin Scale score of 4-6 at 90 days.ResultsOverall, 223 target patients were enrolled in the study. Multivariable analysis showed the larger PHE expansion is the independent risk factors for poor prognosis. The predictive value of absolute PHE expansion (AUC=0.776, sensitivity=67.9%, specificity=77.0%) was higher than that of absolute HE (AUC=0.573, sensitivity=41.7%, specificity=87.1%) and HE (>6 ml) (AUC=0.594, sensitivity=23.8%, specificity=95.0%). The best cutoff for early absolute/relative PHE expansion resulting in a poor outcome was 5.96 ml and 31%.ConclusionsEarly PHE expansion was associated with a poor outcome, characterized by a better predictive value than HE.     

A double-injection model of intracerebral hemorrhage in rabbits

We aimed to develop a double-injection model of intracerebral hemorrhage (ICH) in rabbits and to evaluate it as a tool for investigating post-ICH brain injury. Rabbits were injected with 300 μL fresh autologous whole blood into the right basal ganglia. Behavioral changes were rated, brain water content (BWC) was measured and brain tissue morphology was also examined. ICH was established in 93.5% of the blood injection group. At 1, 3 and 7 days after ICH, there were significant differences in the total neurological scores (p < 0.01) and BWC (p < 0.01) between a sham-operated group and the ICH group. These findings suggest that the model produces a persistent neurological deficit, hematoma volume and perihematomal edema and closely mimics human hypertensive basal ganglia ICH; it is a controllable and reproducible hematoma that lends itself to quantitative investigation.     

Brain tissue oxygen monitoring in intracerebral hemorrhage

Introduction: Brain tissue oxygen (P_brO₂) monitoring is an emerging technique for detection of secondary brain injury in neurocritical care. Although it has been extensively reported in traumatic brain injury and aneurysmal subarachnoid hemorrhage, its use in nontraumatic intracerebral hemorrhage (ICH) has not been well described. We report complementary preliminary studies in a large animal model and in patients that demonstrate the feasibility of P_brO₂ monitoring after ICH. Methods: To assess early events after ICH, Licox Clark-type oxygen probes were inserted in the bilateral frontal white matter of four anesthetized swine that subsequently underwent right parietal hematoma formation in an experimental model of ICH. Intracranial pressure (ICP) was monitored as well. Seven patients with acute ICH, who were undergoing ICP monitoring as part of standard neurocritical care, had placement of a frontal oxygen probe, with subsequent monitoring for up to 7 days. Results: In the swine ICH model, a rise in ICP early after hematoma formation was accompanied by a decrease in ipsilateral and contralateral P_brO₂. Secondary increases in hematoma volume resulted in further decreases in P_brO₂ over the first hour after ICH. In patients undergoing oxygen monitoring, low P_brO₂ (<15 mmHg) was common. In these patients, changes in F_iO₂, mean arterial pressure, and cerebral perfusion pressure (but not ICP) predicted subsequent change in P_brO₂. Conclusion: Brain tissue oxygen monitoring is feasible in ICH patients, as well as in a swine model of ICH. Translational research that emphasizes complementary information derived from human and animal studies may yield additional insights not available from either alone.     

脑出血后继发性脑损伤的机制与治疗

脑出血具有高发病率和高死亡率的特点。近年研究表明，脑出血产生的继发性脑损伤机 制主要涉及凝血酶诱导、红细胞裂解、毒性反应、氧化损伤和炎症反应等多个方面。根据不同的损 伤机制，应运而生了多种脑出血的治疗策略，但是否能成功应用于临床还有待进一步研究。本文对脑 出血后继发性损伤的潜在机制和新兴治疗方法进行了综述。