高血压脑出血血肿周围组织血—脑屏障变化的动脉观察

目的 动态观察高血压脑出血血肿周围组织血-脑屏障的变化。方法 对6例高血压脑出血患者实施立体定向血肿碎吸术,术中取血肿周围少许脑组织进行超微病理观察。结果 血-脑屏障的损伤与出血时间的长短呈正比。脑出血后24h,可见星形胶质细胞肿胀,部分细胞崩解、坏死。毛细血管周围细胞足突肿胀,血-脑屏障损坏。72h,部分星形胶质细胞高度肿胀,细胞器溶解。毛细血管内皮细胞胞核增大,胞质突入管腔,内皮细胞间紧密连接消失。4-7d,星形细胞高度肿胀,胞质内充满水肿液,细胞器消失,细胞变性。毛细血管星形细胞足突明显肿胀,血管周围可见微小出血灶。结论 血-脑屏障的变化与患者的预后有密切关系。     

高血压脑出血血肿周围组织血-脑屏障变化的动态观察

目的动态观察高血压脑出血血肿周围组织血-脑屏障的变化.方法对6例高血压脑出血患者实施立体定向血肿碎吸术,术中取血肿周围少许脑组织进行超微病理观察.结果血-脑屏障的损伤与出血时间的长短呈正比.脑出血后24h,可见星形胶质细胞肿胀,部分细胞崩解、坏死.毛细血管周围细胞足突肿胀,血-脑屏障损坏.72h,部分星形胶质细胞高度肿胀,细胞器溶解.毛细血管内皮细胞胞核增大,胞质突入管腔,内皮细胞间紧密连接消失.4～7d,星形细胞高度肿胀,胞质内充满水肿液,细胞器消失,细胞变性.毛细血管星形细胞足突明显肿胀,血管周围可见微小出血灶.结论血-脑屏障的变化与患者的预后有密切关系.     

高血压脑出血血肿周围组织血-脑屏障变化的动态观察

目的动态观察高血压脑出血血肿周围组织血-脑屏障的变化.方法对6例高血压脑出血患者实施立体定向血肿碎吸术,术中取血肿周围少许脑组织进行超微病理观察.结果血-脑屏障的损伤与出血时间的长短呈正比.脑出血后24 h,可见星形胶质细胞肿胀,部分细胞崩解、坏死.毛细血管周围细胞足突肿胀,血-脑屏障损坏.72 h,部分星形胶质细胞高度肿胀,细胞器溶解.毛细血管内皮细胞胞核增大,胞质突入管腔,内皮细胞间紧密连接消失.4～7 d,星形细胞高度肿胀,胞质内充满水肿液,细胞器消失,细胞变性.毛细血管星形细胞足突明显肿胀,血管周围可见微小出血灶.结论血-脑屏障的变化与患者的预后有密切关系.     

头颅瞬间侧向旋转对脑微血管超微结构的影响

目的研究大鼠头颅瞬间侧向旋转致伤对脑微血管超微结构的影响.方法SD大鼠12只,等分为对照组、伤后2小时观察组、伤后24小时观察组.将大鼠头颅瞬间侧向旋转90°制作脑损伤模型.每组2只经多聚甲醛-戊二醛灌注固定,透射电镜观察延髓组织;另2只依次灌注戊二醛及多聚树脂预聚体,延髓组织经盐酸消化后,扫描电镜观察血管铸型.结果头颅瞬间侧向旋转后2～24小时,毛细血管收缩、狭窄;管外有水肿间隙;管周胶质足突肿胀,内皮细胞变性,管壁局部不全或完全断裂;管内微血栓形成.结论头颅瞬间侧向旋转可致脑微血管的超微形态与结构发生破坏,造成微循环功能异常,这是DAI病理生理变化的重要基础,改善脑微循环有利于DAI的临床治疗.     

高血压脑出血患者血肿周围血-脑屏障超微结构的观察

目的 动态观察高血压脑出血后不同时间血肿周围血-脑屏障（BBB）的超微结构。方法 选取10例基底节区高血压脑出血患者,通过CT导向脑立体定向仪在血肿周围取脑组织标本,电镜下观察BBB的超微结构。结果：脑出血12h后BBB胶质足板水肿,胞饮水泡增多,24h后内皮细胞线粒体肿胀,嵴断裂,48h后足板水肿明显,内皮细胞水肿,细胞核增大;72h胞质稀疏,基底膜断开;5d内皮细胞胞膜及核膜溶解,毛细血管塌陷。结论 脑出血早期预防BBB的损害是治疗脑出血的重要方面。     

星形细胞瘤瘤周水肿区立体定向活检组织的超微结构研究

目的探讨星形细胞瘤瘤周脑水肿的发生机制。方法对15例星形细胞瘤瘤周脑水肿的宽度进行分级：一级0～20mm、二级21～40mm、三级〉40mm。结合CT平扫及增强扫描的影像，应用立体定向技术，对15例星形细胞瘤瘤体、瘤周水肿区及正常脑组织的活检标本进行电镜观察比较。结果CT增强扫描可强化，瘤周脑水肿明显的病人，其瘤体及瘤周水肿区毛细血管超微结构均有不同程度的改变。毛细血管的分布和结构变化，影响着瘤周水肿区的形态，瘤体毛细血管的明显异常，出现于大范围瘤周水肿区的病例。CT增强扫描无强化，瘤周脑水肿不明显的病人，毛细血管超微结构与正常脑组织相似。结论伴有明显瘤周脑水肿的星形细胞瘤，其瘤体及瘤周水肿区毛细血管超微结构均有不同程度的改变，而瘤周水肿的产生，是瘤体及瘤周水肿区毛细血管超微结构改变共同作用的结果。     

脑过度灌注动物模型的血脑屏障超微结构研究

目的 从形态学基础探讨脑过度灌注的发生机理。方法 透射电镜下观察不同时相的脑盗血和脑过度灌注动物局部脑组织超微结构。结果 慢性脑盗血大鼠毛细血管周围星形胶质细胞足突层（AsF)肿胀，胞浆稀疏呈空泡化，AsF层空泡化程度较急性、亚急性者严重（P＜0．01）。邻近的星形胶质细胞（As)出现相似的空泡化等改变，神经元细胞（NC）形态改变不如As明显。脑过度灌注发生后，慢性脑盗血区BBB结构完整性严重破坏。结论 在慢性脑盗血状态下，As最先发生形态学异常。BBB超微结构的改变以AsF层空泡化为特征，构成了脑过度灌注发生的形态学基础。当脑微血管网承受血流高灌注时，BBB进一步破坏，组织水肿形成。     

脑胶质瘤瘤周CT低密度区的病理和超微结构研究

为阐明脑胶质瘤瘤周CT低密度区（CT－PTLDA）本质及其与预后的关系，本研究对20例胶质瘤瘤周CT低密度区的宽度进行分级，并以光镜观察其病理特征；结合CT平扫及增强扫描的影像，取代表性的14例肿瘤瘤体、水肿区和正常脑组织进行电镜观察比较。结果显示：（1）CT－PTLDA内可见瘤细胞浸润；（2）电镜下可见瘤体及瘤周毛细血管内皮细胞呈不同程度肿胀，紧密连接扩张、扭曲，基膜完整但厚薄不均，胶质膜局部缺损。CT－PTLDA越宽其血脑屏障改变也越严重；（3）CT－PTLDA宽度与预后密切相关，CT－PTLDA越宽预后越差。以上结果提示脑胶质瘤CT－PTLDA是瘤细胞浸润扩散的实际范围及伴有脑水肿的表现，对CT－PTLDA宽度进行分级有助于对预后的判断。笔者建议在胶质瘤手术中应尽可能切除非功能区组织的水肿带，以免留下肿瘤复发根源。     

脑星形细胞瘤瘤周水肿区活检组织病理及超微结构研究

目的 探讨星形细胞瘤瘤周脑水肿区的病理及发生水肿可能机制。方法 对15例星形细胞瘤瘤周水肿的宽度进行分级,共分三级：一级0-20mm、二级21-40mm、三级〉41mm。并对其立体定向多靶点活检组织进行光镜及电镜检查。结果 在星形细胞瘤瘤周水肿区内,发现有浸润的肿瘤细胞,肿瘤细胞形态与瘤体区标本的肿瘤细胞形态一致。随着肿瘤恶性度及瘤周水肿程度的增加,肿瘤细胞浸润的范围就更广。瘤体和瘤周水肿区毛细血管的分布和结构变化影响着瘤周水肿区的形态,瘤体毛细血管的明显异常,出现于大范围瘤周水肿区的病例。结论 脑星形细胞瘤瘤周水肿区是肿瘤浸润的范围,伴有脑水肿。瘤体及瘤周水肿区毛细血管超微结构均有不同程度的改变。     

少突胶质细胞瘤,IDH-突变和1p/19q-共缺失

正2016年世界卫生组织(WHO)中枢神经系统肿瘤分类将"少突胶质细胞瘤,异柠檬酸脱氢酶(IDH)-突变和1p/19q-共缺失"定义为弥漫性浸润、生长缓慢、IDH1/2-突变、染色体1p/19q-共缺失的胶质瘤。组织学形态,肿瘤组织由形态类似少突胶质细胞的肿瘤细胞组成,胞核圆形、大小较一致,胞质肿胀、透亮;典型病例常可见微钙化、分支状毛细血管,亦可见星形细胞瘤样成分(图1)。免疫组织化学染色,多数肿瘤细胞胞质强阳性表达R132H-突变的IDH1(图2a),较少细胞胞核表达P53,由于肿瘤缺乏ATRX突变,常可见胞核表达ATRX(图2b),小肥胖细胞和神经胶质纤维性少突胶质细胞胞质表达胶质纤维酸性蛋白     

大鼠弥漫性颅脑损伤后脑水肿和病理学变化

目的探讨大鼠弥漫性颅脑损伤后病理学变化规律及意义。方法成年健康SD雄性大鼠100只，以自由落体法建立大鼠弥漫性颅脑损伤模型，随机平均分为对照组及外伤后1h、3h、6h、12h、24h、48h、72h、7d和14d等10组．检测大鼠脑组织含水量并观察脑组织中炎症反应、毛细血管和神经元的结构变化。结果外伤后脑皮层组织含水量呈上升趋势．3h含水量有较大幅度升高，24h达高峰，其后下降，14d时仍处于较高水平，伤后6、12、24、48和72h组与对照组相比．脑组织含水量明显高于对照组（P〈0．05）。脑组织炎症反应、毛细血管和神经元结构变化与脑水肿变化相平行。结论弥漫性颅脑损伤后发生缺血、缺氧．导致微循环障碍，最终血-脑屏障结构破坏，神经细胞的代谢活动紊乱，使脑组织发生继发性脑损伤。弥漫性颅脑损伤后脑水肿是造成继发性脑损伤病理学变化的基础。     

Trauma-induced cell swelling in cultured astrocytes

Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.     

Time course of aquaporin expression after transient focal cerebral ischemia in mice

Cerebral edema contributes to morbidity and mortality in stroke. Aquaporins (AQPs)-1, -4, and -9 have been identified as the three main water channels in the brain. To clarify their role in water movement, we have compared their expression patterns with brain swelling after transient focal brain ischemia. There were two peaks of maximal hemispheric swelling at 1 hr and at 48 hr after ischemia, coinciding with two peaks of AQP4 expression. At 1 hr after occlusion, AQP4 expression was significantly increased on astrocyte endfeet in the core and in the border of the lesion. At 48 hr, AQP4 expression was increased in astrocytes in the border of the lesion over the whole cell. AQP9 showed a significant induction at 24 hr that increased gradually with time, without correlation with the swelling. The expression of AQP1 remained unchanged. These results suggest that AQP4, but not AQP1 or AQP9, may play an important role in water movement associated with the pathophysiology of edema after transient cerebral ischemia in the mouse.     

Inhibitors of the mitochondrial permeability transition reduce ammonia‐induced cell swelling in cultured astrocytes

Ammonia is the principal neurotoxin implicated in the pathogenesis of hepatic encephalopathy, and astrocytes are the neural cells predominantly affected in this condition. Astrocyte swelling (cytotoxic edema) represents a critical component of the brain edema in acute form of hepatic encephalopathy (acute liver failure, ALF). Although mechanisms of astrocyte swelling by ammonia are not completely understood, cultured astrocytes exposed to pathophysiological levels of ammonia develop the mitochondrial permeability transition (mPT), a process that was shown to result in astrocyte swelling. Cyclosporin A (CsA), a traditional inhibitor of the mPT, was previously shown to completely block ammonia‐induced astrocyte swelling in culture. However, the efficacy of CsA to protect cytotoxic brain edema in ALF is problematic because it poorly crosses the blood–brain barrier, which is relatively intact in ALF. We therefore examined the effect of agents that block the mPT but are also known to cross the blood–brain barrier, including pyruvate, magnesium, minocycline, and trifluoperazine on the ammonia‐induced mPT, as well as cell swelling. Cultured astrocytes exposed to ammonia for 24 hr displayed the mPT as demonstrated by a CsA‐sensitive dissipation of the mitochondrial inner membrane potential. Pyruvate, minocycline, magnesium, and trifluoperazine significantly blocked the ammonia‐induced mPT. Ammonia resulted in a significant increase in cell volume, which was blocked by the above‐mentioned agents to a variable degree. A regression analysis indicated a high correlation between the effectiveness of reducing the mPT and cell swelling. Our data suggest that all these agents have therapeutic potential in mitigating brain edema in ALF. © 2009 Wiley‐Liss, Inc.     

Aquaporin 4 expression and ultrastructure of the blood-brain barrier following cerebral contusion injury

This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2–72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelial cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.     

Vascular aspects of neuroprotection

It is being increasingly suggested that the microcirculation, which is known to be in a large part responsible for maintaining an adequate and constant microenvironment for function of the central nervous system, functions as part of a neurovascular unit. The neurovascular unit includes neurons, astrocytes and elements of capillaries. The cerebral circulation exhibits unique functional characteristics and critical elements for the pathogenesis of cerebrovascular disease. For example, the blood-brain barrier formed by epithelial-like high resistance tight junctions within the endothelium is a key feature of microvessels of the central nervous system. Alterations in the microcirculation after ischemia/reperfusion include disruption of the blood-brain barrier, edema and swelling of perivascular astrocyte foot processes, decrease in arteriole endothelium-dependent relaxation and reduced inwardly-rectifying potassium channel function, altered expression of proteases and matrix metalloproteinases, increased inflammatory mediators and inflammation. Experiments studying the microcirculation in ischemia are few compared with those examining neuroprotection, although the two overlap because protection of the microcirculation might achieve some degree of neuroprotection and both processes may be mediated by at least some mechanisms in common.     

颅脑损伤后炎性细胞的变化及其与继发性脑损伤的关系

目的探讨颅脑损伤后患者外周血白细胞（WBC）及多形核嗜中性白细胞（PMN）的变化及其在继发性脑损害中的作用。方法选取伤后24h内入院的非手术治疗的颅脑损伤患者63例,于入院时、入院后24h、48h、72h及168h不同时间段采外周静脉血进行白细胞计数及分类,同时进行GCS评分,计算脑出血量及脑水肿体积,伤后6个月进行GOS评分,分析上述指标与WBC和PMN之间的关系。选取10例健康自愿者行WBC及PMN计数检查。结果颅脑损伤以后WBC及PMN先升高后下降,分别于伤后24h和48h达到高峰（P〈0.05）;伤后WBC及PMN与GCS评分呈负相关（P〈0.05）,GCS〈8分组WBC和PMN计数显著高于GCS≥8分组（P〈0.05）;颅脑损伤后脑出血量及脑水肿体积与WBC及PMN呈正相关（P〈0.05）;GOS评分与WBC及PMN呈负相关（P〈0.05）。结论颅脑损伤后WBC及PMN明显升高,且与伤情、出血量、水肿体积及预后有关,可能跟WBC及PMN对颅脑损伤后引起的继发性损害有关,WBC和PMN计数有助于对伤情、预后的判断。     

Role of mitogen‐activated protein kinases in the mechanism of oxidant‐induced cell swelling in cultured astrocytes

Cytotoxic brain edema, usually a consequence of astrocyte swelling, is an important complication of stroke, traumatic brain injury, hepatic encephalopathy, and other neurological disorders. Although mechanisms underlying astrocyte swelling are not fully understood, oxidative stress (OS) has generally been considered an important factor in its pathogenesis. To better understand the mechanism(s) by which OS causes cell swelling, we examined the potential involvement of mitogen‐activated protein kinases (MAPKs) in this process. Cultures exposed to theoxidant H₂O₂ (10, 25, 50 μM) for different time periods (1–24 hr) significantly increased cell swelling in a triphasic manner. Swelling was initially observed at 10 min (peaking at 30 min), which was followed by cell shrinkage at 1 hr. A subsequent increase in cell volume occurred at approximately 6 hr, and the rise lasted for at least 24 hr. Cultures exposed to H₂O₂ caused the activation of MAPKs (ERK1/2, JNK and p38‐MAPK), whereas inhibition of MAPKs diminished cell swelling induced by 10 and 25 μM H₂O₂. These findings suggest that activation of MAPKs is an important factor in the mediation of astrocyte swelling following oxidative stress. © 2010 Wiley‐Liss, Inc.     

弥漫性脑损伤大鼠丘脑网状核代谢性谷氨酸受体变化及意义

目的 研究大鼠弥漫性脑损伤(DBI)时丘脑网状核(TRN)中代谢性谷氨酸受体la(mGluRla)的表达水平变化及其意义.方法 雄性SD大鼠45只按随机数字表法分为正常组(不处理)、假手术组(仅固定并切开头皮处理)与DBI组(固定,重物打击颅脑处理),每组又按不同处死时间(造模后6、12和24h)分为3个亚组,每亚组5只.光镜观察脑组织病理变化,并采用免疫组化等方法检测TRN区mGluRla表达变化情况.结果 与正常组和假手术组比较.DBI组的mGluRla表达水平随时间延长而增高,12h时显著上调.24h时略有恢复,但表达水平仍很高,与其余两组比较.差异有统计学意义(P=0.000).结论 大鼠DBI后mGluRla表达水平显著增高,推测其为加重神经元损伤的主导因素.     

Aquaporin expression in the brains of patients with or without cerebral amyloid angiopathy

Aquaporins have recently been identified as protein channels involved in water transport. These channels may play a role in the edema formation and alterations in microvascular function observed in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). We investigated the expression of aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in 24 human autopsy brains consisting of 18 with AD and varying degrees of CAA and 6 with no pathologic abnormalities using immunohistochemistry. In cases of AD and CAA, there was enhanced AQP4 expression compared with the age- and sex-matched controls. Aquaporin 4 immunoreactivity was prominent at the cerebrospinal fluid and brain interfaces, including subpial, subependymal, pericapillary, and periarteriolar spaces. Aquaporin 1 expression in AD and CAA cases was not different from that in age- and sex-matched controls. Double labeling studies demonstrated that both AQP1 and 4 were localized to astrocytes. Both enhanced AQP4 expression and its unique staining pattern suggest that these proteins may be important in the impaired water transport observed in AD and CAA.