综述与专论: 高压氧疗法治疗脑缺血的相关机制

脑缺血是指大脑各部分血液供应不足导致脑组织缺血缺氧，进而导致密集缺血区脑组织出现不可逆的损伤坏死，其高致残率、高死亡率会对患者及其家庭造成严重的伤害。在脑缺血发生后，及时采取一定的治疗措施控制梗死灶的大小，并挽救半暗带中的细胞是脑缺血预后的关键。高压氧疗法是针对脑缺血的一种潜在治疗方法，在近年来得到了越来越广泛的关注和研究，本文旨在综述近年来国内外关于高压氧疗法治疗脑缺血的相关机制及研究进展，为脑缺血患者的治疗和预后提供新思路。     

CEREBRAL VASCULAR DISEASES—Certain Clinical and Electroencephalographic Aspects

In a preliminary study of 52 patients with cerebral vascular disease, clinical and electroencephalographic evaluations were compared. Most of the patients were in the sixth and seventh decade of life and had had symptoms of cerebral vascular disease for over a year. Seventeen of the patients had clinical evidence of intermittent cerebral ischemia. When routine electroencephalographic techniques were used, 47 per cent of the records were within normal limits. Twenty patients with cerebral vascular disease, eight of whom had clinical cerebral vascular insufficiency, were studied during posturally induced hypotension. No activation was detected in any of these 20 patients. It would appear that other methods of activation, including tilt-table studies, and serial recordings should be further explored and evaluated in these disorders if more clinically useful information is to be gained.     

Cerebral vascular diseases; certain clinical and electroencephalographic aspects

In a preliminary study of 52 patients with cerebral vascular disease, clinical and electroencephalographic evaluations were compared. Most of the patients were in the sixth and seventh decade of life and had had symptoms of cerebral vascular disease for over a year. Seventeen of the patients had clinical evidence of intermittent cerebral ischemia. When routine electroencephalographic techniques were used, 47 per cent of the records were within normal limits. Twenty patients with cerebral vascular disease, eight of whom had clinical cerebral vascular insufficiency, were studied during posturally induced hypotension. No activation was detected in any of these 20 patients. It would appear that other methods of activation, including tilt-table studies, and serial recordings should be further explored and evaluated in these disorders if more clinically useful information is to be gained.     

对比不同类型干细胞对于缺血性脑卒中治疗的研究进展

成人中枢神经系统存在着一定量的神经干细胞,其具有两大关键能力;自我更新和多向分化潜能。缺血性脑卒中是一种由于由脑血流的缺失或减少引起的脑动脉闭塞,进而导致脑组织梗死的脑血管疾病。虽然对于脑损伤的药物治疗已经取得了一定的成果,但目前以干细胞为基础的治疗方法仍成为了研究热点。无论是内源性神经干细胞还是外源性神经干细胞移植均可在脑损伤后向远端损伤区迁移并分化成新的神经细胞,从而在中枢神经系统疾病尤其是脑梗死后进行组织修复和功能恢复。因此在这篇综述中,我们主要探讨不同类型的干细胞对脑梗死介导的脑损伤的应用潜能,对比不同类型干细胞对缺血性脑卒中的治疗优缺点。     

脑出血后白质微观结构损伤与血管性认知功能障碍的相关性研究

目的:探讨脑出血后白质微观结构损伤情况和血管性认知功能功能障碍(VCI)的相关性。方法:选择2012年1月至2017年12月我院收治的脑出血患者50例作为研究对象,所有患者按照神经心理学评估结果分为认知功能障碍组(A组)29例和认知正常组(B组)21例,观察和比较两组患者病灶情况和白质微观结构的改变情况。结果:A组患者额区、基底核区病灶数量,病灶直径、白质病变、美国国立卫生院卒中量表(NIHSS)_评分等指标均明显高于B组,改良巴氏指数(MBI)评分低于B组(P0.05);将蒙特利尔认知评估(MoCA)量表评分作为因变量,MBI评分和NIHSS量表评分、病灶直径、病灶数量、白质病变程度等作为自变量进行多元Logistic回归分析,结果显示白质病变程度是脑出血患者VCI独立危险因素(P0.05)。结论:脑出血患者白质缺血性病变程度可能用于评估其发生VCI的风险。     

颅内静脉系统血栓形成合并脑出血的临床特点、危险因素、诊断方法以及治疗方案分析

目的:探讨颅内静脉系统血栓形成(CVST)合并脑出血的临床特点、危险因素、诊断方法以及治疗方案。方法:选择我院于2002年2月到2017年5月收治的CVST确诊患者38例为研究对象,按照是否合并脑出血分为脑出血组16例与对照组22例,比较两组患者的临床特点、危险因素、诊断方法、治疗方案与预后。结果:脑出血患者MRI显示受累横窦8例、海绵窦6例、乙状窦2例;对照组显示受累横窦10例、海绵窦8例、乙状窦4例。脑出血组的头痛、意识改变、运动障碍等临床症状发生率明显高于对照组(P0.05),两组感觉障碍、视力下降与痫性发作比例对比差异无统计学意义(P0.05)。二分类变量Logistic回归分析显示脑膜炎、贫血、先天性凝血酶原疾病为导致CVST合并脑出血发生的主要独立危险因素(P0.05)。所有患者均给予脱水降颅压及支持对症治疗,脑出血组预后不良8例,不良率为50.0%;对照组预后不良4例,不良率为18.2%,脑出血组的预后不良率明显高于对照组(P0.05)。结论:CVST合并脑出血在临床上比较常见,多表现为头痛、意识改变、运动障碍等,MRI诊断有很好的效果,脑膜炎、贫血、先天性凝血酶原疾病为导致CVST合并脑出血发生的危险因素,抗凝、溶栓等治疗能取得较好的效果。     

Observations in five cases of spontaneous cerebellar hemorrhage

Five cases of spontaneous intracerebellar hemorrhage are reported. Three had a vascular malformation and two had mild hypertension. The presenting symptom was sudden headache followed by nausea and vomiting. Signs of brain stem dysfunction without prominent cerebellar deficit were the commonest feature. Meningeal involvement was present in the majority of cases. Unsuspected sudden death can occur. It is suggested that patients below the age of 30 who present with sudden headache followed by brain stem dysfunction with or without a subarachnoid hemorrhage, and patients over the age of 45 who present this picture along with subarachnoid hemorrhage should be investigated urgently with contrast studies for possible cerebellar hemorrhage.     

Local and global cerebral blood flow and glucose utilization in the α-galactosidase A knockout mouse model of Fabry disease

Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency.     

Propofol Reduces Inflammatory Reaction and Ischemic Brain Damage in Cerebral Ischemia in Rats

Our previous studies demonstrated that inflammatory reaction and neuronal apoptosis are the most important pathological mechanisms in ischemia-induced brain damage. Propofol has been shown to attenuate ischemic brain damage via inhibiting neuronal apoptosis. The present study was performed to evaluate the effect of propofol on brain damage and inflammatory reaction in rats of focal cerebral ischemia. Sprague–Dawley rats underwent permanent middle cerebral artery occlusion, then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 h of ischemia. Neurological deficit scores, cerebral infarct size and morphological characteristic were measured 24 h after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was assessed 24 h after cerebral ischemia. Nuclear factor-kappa B (NF-κB) p65 expression in ischemic rat brain was detected by western blot. Cyclooxygenase-2 (COX-2) expression in ischemic rat brain was determined by immunohistochemistry. ELISA was performed to detect the serum concentration of tumor necrosis factor-α (TNF-α). Neurological deficit scores, cerebral infarct size and MPO activity were significantly reduced by propofol administration. Furthermore, expression of NF-κB, COX-2 and TNF-α were attenuated by propofol administration. Our results demonstrated that propofol (10 and 50 mg/kg) reduces inflammatory reaction and brain damage in focal cerebral ischemia in rats. Propofol exerts neuroprotection against ischemic brain damage, which might be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory genes.     

Recovery of breathing pattern after 15 min of cerebral ischemia in rabbits

The study was undertaken to ascertain the neural control of breathing and vagal reflexes during and after cerebral ischemia. The experiments were performed on anesthetized, paralyzed, and artificially ventilated rabbits. Cerebral ischemia was induced by reversible intrathoracic occlusion of the brachiocephalic trunk and the left subclavian and both internal thoracic arteries for 15 min. The effect of cerebral ischemia on breathing pattern was assessed by monitoring the integrated activities of phrenic and recurrent laryngeal nerves. Ischemia produced enhancement of breathing followed by apnea and gasping. During enhanced breathing as well as during gasping, the inspiratory-inhibiting effect of lung inflation (Breuer-Hering reflex) was abolished. When brain circulation was restored, respiratory activity started with gasps, which later were intermingled with eupneic type of inspirations. During the onset of a eupneic breath, lung inflation produced inspiratory facilitation but never an inhibition. However, after 30 min of recovery from cerebral ischemia, the Breuer-Hering reflex was restored. Results show that precise analysis of vagal reflexes and respiratory pattern during ischemia and resuscitation may be used as an indicator of resumption of autonomic activity in the brain stem.     

Delayed injection of neural progenitor cells improved spatial learning dysfunction after cerebral ischemia

Although stem cells are likely to improve neurological deficits seen after cerebral ischemia, the effects of neural progenitor cells (NPCs) on cerebral ischemia-induced learning dysfunction remain to be clarified. We tested whether the delayed injection of exogenous NPCs could prevent learning dysfunction after cerebral ischemia. Cerebral ischemia was produced by the injection of microspheres into the right hemisphere of each rat. Injection of NPCs obtained from green fluorescent protein transgenic rats into the hippocampus on Day 7 after the induction of cerebral ischemia improved the modified neurological severity score and reduced the prolongation of the escape latency seen in the water maze task. A few of the injected NPCs were positive for mature neuronal markers. In addition, the injected NPCs expressed BDNF on Day 28 after cerebral ischemia. Thus, the exogenous NPCs delivered by injection could act as a source of neurotrophic factors and prevent cerebral ischemia-induced learning dysfunction.     

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24 h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.     

P300 component changes of the auditory event-related potential in the patients with typical and atypical panic attacks

84 patients with panic disorders and 36 healthy control subjects with use of clinico-neurologic technique, psychometric, neuropsychological and the neurophysiological method of auditory event-related potentials P300 were examined. Patients with panic disorders were characterized by the raised level of anxiety, depression and cognitive function disturbances in the form of decrease of short-term memory and attention insufficiency in comparison with the healthy control subjects. Patients with atypical panic disorders differed from the patients with typical panic disorders by lower level of anxiety, a greater degree of depression and more expressed cognitive function disturbances. In comparison with the healthy control subjects with atypical panic disorders the decrease of P300 peak amplitude was observed, with typical--its augmentation. It is supposed, that P300 peak change is bound to dysfunction of temporal-limbic-reticular brain structures.     

Effects of ischemia/reperfusion on brain tissue prostanoids and leukotrienes in newborn pigs.

We investigated the hypothesis that cerebral prostanoid and peptidoleukotriene (LTs) (LTC4/D4/E4/F4) synthesis are increased during postischemic reperfusion of newborn pig brains. Prostanoids and LTs extracted from brain tissue were determined by RIA in sham-control piglets and at 1h, 3h, or 12h after a 20-min period of total cerebral ischemia. During reperfusion following ischemia, all regional brain tissue (cerebrum, brain stem and cerebellum) prostanoids (6-keto-PGF1 alpha, TXB2, PGE2 and PGF2 alpha) were increased at 1h compared with those in sham-control piglets. Only cerebral and brain stem 6-keto-PGF1 alpha and cerebral TXB2 remained elevated at 3h postischemia and all prostanoids returned to control levels by 12h postischemia. Brain tissue LTs were lower than prostanoids and were not altered 1, 3, or 12h following ischemia. These data indicate that 1) newborn pig brain tissue prostanoids are increased initially, and then returned to control levels at later stages of reperfusion following ischemia; 2) LTs are present in newborn pig brain tissue, but are not increased by ischemia/reperfusion injury and therefore probably do not play a significant role in cerebral ischemia-reperfusion injury.     

Cognitive disorder in brain concussion

This paper presented original study results concerning the prevalence and clinical characteristics of cognitive impairment associated with brain concussion. The cognitive functions of 80 consecutive patients （mean age = 37.40±1l.74years; 50 men and 30 women） admitted to the hospital with brain concussions were evaluated. Their cognitive scores were compared with 40 age- and education-matched healthy volunteers without history of cranial trauma. Cognitive impairment without dementia was found in 93% of the patients. Cognitive impairment in brain concussion was also characterized by prominent cognitive slowness （bradyphrenia）, concentration decrease, free recall insufficiency, and visual-spatial dysfunction. Age and severity of anxiety significantly influence the cognitive performance of patients.     

两种治疗方案对脑出血病人康复的影响

脑卒中是急性的脑部血液循环障碍造成的局部脑损害,又叫中风或脑血管意外,是现代中老年人健康的重要威胁,脑出血是其中的一种情况。采用由引导放松干预治疗的方法对脑出血患者进行护理干预,通过监测患者的血压、呼吸以及心率变化来判定干预效果,同时通过CT扫描来判定康复效果。干预结果表明：引导放松这种护理干预能够通过有效的稳定患者的收缩压和舒张压促进患者的康复。研究表明引导放松干预治疗对脑卒中病人的治疗具有一定的推广应用价值。     

Induced pluripotent stem cells and Parkinson's disease: modelling and treatment

Many neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hiPSCs, as well as the potential value of hiPSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment.     

远端缺血后处理对脑缺血保护作用的研究进展

近20多年来人们对脑缺血损伤的保护研究很多,但真正能将脑缺血保护从基础研究应用到临床治疗的措施甚少。多数基础研究表明缺血预处理对大鼠脑缺血具有保护作用,然而由于脑缺血的不可预见性,研究者们将目标转向了缺血后处理。远端缺血后处理是指在非缺血器官交替实施短时间的缺血和再灌注后对缺血器官所产生的作用。由于脑组织本身对缺血的敏感,很难控制缺血后处理的程度,因此远端缺血后处理被应用到脑缺血的保护研究具有很强的临床应用价值,其机制可能与氧自由基、神经传导、蛋白质、内质网应激、Akt信号通路、线粒体途径、mitoKATP和阿片受体有关。本文主要就近几年远程缺血后处理对脑缺血保护的概念、实施方法、保护作用及分子机制做一综述。     

Erythropoietin for the Treatment of Subarachnoid Hemorrhage: A Feasible Ingredient for a Successful Medical Recipe

Subarachnoid hemorrhage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Although an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbidity and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm. In recent years, the mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been investigated intensively. A number of pathological processes have been identified in the pathogenesis of vasospasm, including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. To date, the current therapeutic interventions remain ineffective as they are limited to the manipulation of systemic blood pressure, variation of blood volume and viscosity and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO) has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is administered systemically. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the current review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrhage.     

Sleepwalking,night terrors,and consciousness.

OBJECTIVE--To determine some personality and psychoneurotic characteristics of adults who have the sleepwalking-night terrors syndrome. DESIGN--Prospective assessment of two groups of consecutive patients with a firm diagnosis of either of two specific sleep disorders as established clinically and by polysomnography. SETTING--Outpatient sleep disorders clinic and sleep laboratory in a tertiary referral centre. PATIENTS--12 Patients referred consecutively to the clinic in whom a diagnosis of sleepwalking (six) or night terrors (six) was confirmed. MAIN OUTCOME MEASURES--Psychological characteristics as measured at the time of clinical assessment by means of the Eysenck personality questionnaire, the hostility and direction of hostility questionnaire, and the Crown-Crisp experiential index. RESULTS--Both groups scored exceptionally highly on the hysteria scale of the Crown-Crisp experiential index and the night terrors group also scored highly on the anxiety scale. The patients with sleepwalking also scored highly on a measure of externally directed hostility. CONCLUSIONS--The physiological and psychological features identified in these patients, possibly reflecting different expressions of a constitutional cerebral characteristic, may be explored in terms of hysterical dissociation. The findings contribute to the debate concerning the nature of sleepwalking, in particular with and without the forensic aspects.