氧化应激在慢性缺血性脑白质损伤中的作用

目的 阐明氧化应激是否参与大鼠慢性脑缺血所致的脑白质损伤.方法 健康雄性Wistar大鼠按照完全随机数字表法分为假手术组,持久性双侧颈总动脉结扎3 d组、7 d组、3周组及6周组,每组6只.应用大鼠双侧颈总动脉结扎制备慢性脑缺血模型,检测大鼠脑白质内超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、谷胱甘肽(GSH)含量以及脂质过氧化产物丙二醛(MDA)和4-羟基壬烯醛(4-HNE)加合物的变化.结果 与假手术组比较,慢性脑缺血大鼠脑白质内MDA含量在手术后3周明显增加,手术后6周进一步增高,差异有统计学意义(P<0.05).手术后3d至6周,慢性脑缺血大鼠脑白质内4-HNE蛋白加合物逐渐增高,与假手术组比较有差异有统计学意K(P<0.05).SOD活性在手术后3周和6周才明显降低,与假手术组比较差异有统计学意义(P<0.05).此外,慢性脑缺血大鼠脑白质内GSH含量在手术后7d即开始降低,而在手术后3周及6周则进一步下降,与假手术组比较差异有统计学意义(P<0.05).结论 慢性脑缺血导致大鼠脑白质氧化性损伤增加,抗氧化防御能力降低:氧化性损伤的增加和抗氧化防御能力的降低与慢性脑缺血所致的脑白质损伤密切相关.     

绞股蓝总皂甙对慢性脑缺血性白质氧化性损伤的保护作用

目的 探讨绞股蓝总皂甙对慢性脑缺血大鼠脑白质氧化性损伤的保护作用以及对脑缺血大鼠认知功能的影响.方法 将57只成年雄性SD大鼠按随机数字表法分成假手术组(n=12)、模型组(n=15)、绞股蓝总皂甙200 mg组(n=15)、绞股蓝总皂甙400 mg组(n=15),后3组采用双侧颈总动脉结扎法制备慢性脑缺血模型,且在造模后3h分别将等量生理盐水,200 mg/kg、400mg/kg绞股蓝总皂甙溶液灌胃,1次/d,持续33 d.应用Morris水迷宫实验测试各组大鼠空间学习与记忆能力的改变,酶联免疫吸附法(ELISA)测定大鼠胼胝体、视束内超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,免疫组化染色用8-羟基脱氧鸟苷(8-OHdG)抗体测定中枢神经细胞的氧化损伤水平.结果 与模型组相比,绞股蓝总皂甙400 mg组大鼠的逃避潜伏期明显缩短及在原平台象限的游泳时间明显延长,差异有统计学意义(P＜0.05).与假手术组比较,模型组大鼠胼胝体及视束内MDA含量明显增加,SOD活性明显降低,差异有统计学意义(P＜0.05).与模型组相比,绞股蓝总皂甙400 mg组MDA含量明显降低,SOD活性明显升高,8-OHdG阳性细胞数明显减少,差异有统计学意义(P＜0.05).与模型组相比,绞股蓝总皂甙200 mg组SOD活性、MDA含量及8-OHdG阳性细胞数差异无统计学意义(P＞0.05).结论 绞股蓝总皂甙能有效改善慢性脑缺血大鼠脑白质氧化性损伤,提示其可能是一种有效的抗痴呆药物,但其作用的确切机制还有待进一步研究.     

Dose-dependent, protective effect of FK506 against white matter changes in the rat brain after chronic cerebral ischemia

Neuroprotective effects of immunosuppressive agents have been shown in cerebral ischemia. To investigate the role of immunosuppressive agents in chronic cerebral ischemia and to design a drug protocol with safe therapeutic windows, we examined the effects of FK506, a potent immunosuppressive agent, on chronic cerebral ischemia. Both common carotid arteries were ligated in 73 male Wistar rats. Fifty-eight of these rats received a chronic injection of FK506 (0.2, 0.5, 1.0 mg/kg) and the remaining 15 received a vehicle solution injection. Microglia/macrophage was investigated with immunohistochemistry for leukocyte common antigen and major histocompatibility complex, and astroglia was examined with glial fibrillary acidic protein as markers. White matter rarefaction and the number of immunopositive glial cells were assessed from 7 to 30 days after the ligation. In the vehicle-treated animals, there was persistent and extensive activation of the microglia/macrophages and astroglia in the white matter, including the optic nerve, optic tract, corpus callosum, internal capsule, anterior commissure and traversing fiber bundles of the caudoputamen. In the FK506-treated rats, the number of activated microglia/macrophages was significantly reduced in a dose-dependent manner (p<0.01) as compared to the vehicle-treated rats. Rarefaction of the white matter was also inhibited by FK506 in a dose-dependent manner (p<0.01). Thus, a clinically-relevant dosage of FK506 attenuated both glial activation and white matter changes in chronic cerebral ischemia in the rat. These results indicate a potential use for FK506 in cerebrovascular diseases.     

Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat

Cerebral white matter (WM) lesions are observed frequently in human ischemic cerebrovascular disease and have been thought to contribute to cognitive impairment. This type of lesion can be experimentally induced in rat brains under chronic cerebral hypoperfusion by the permanent occlusion of both common carotid arteries. However, it remains uncertain whether chronic ischemia can damage both the gray and white matter, and whether it can induce demyelination with or without axonal damage. Therefore, we examined axonal damage using immunohistochemistry for the amyloid beta/A4 precursor protein (APP), chromogranin A (CgA) and demyelination using immunohistochemistry for the encephalitogenic peptide (EP) in this model. Severe WM lesions such as vacuolation and the loss of nerve fibers appeared in the optic nerve and optic tract after 3 days of ligation, and less intense changes were observed in the corpus callosum, internal capsule, and fiber bundles of the caudoputamen after 7 days with Klüver-Barrera and Bielschowsky staining. These WM lesions persisted even after 30 days. The APP, CgA, and EP-immunopositive fibers increased in number from 1 to 30 days after the ligation in the following WM regions: the optic nerve, optic tract, corpus callosum, internal capsule, and fiber bundles of the caudoputamen. In contrast, only a few APP, CgA, or EP-immunopositive fibers were detected in the gray matter regions, including the cerebral cortex and hippocampus. These results indicate that the WM is more susceptible to chronic cerebral hypoperfusion than the gray matter, with an involvement of both axonal and myelin components. Furthermore, immunohistochemistry for APP, CgA, and EP is far superior to routine histological staining in sensitivity and may become a useful tool to investigate WM lesions caused by various pathoetiologies.     

血管生成对慢性低灌注状态下血脑屏障及脑白质损害的影响

目的 了解脑血管生成是否参与脑白质区域慢性低灌注状态下血脑屏障的破坏机制。方法 将72只雄性Wistar大鼠随机分为3组:假手术组、脑缺血组、干预组,脑缺血组及干预组大鼠结扎双侧颈总动脉构建慢性低灌注模型,干预组给予血管生成抑制剂灌胃以抑制血管生成; 对各组大鼠在相同时间点检测脑深部白质区域微血管密度、白质纤维密度以及伊文思蓝静脉注射6 h后脑白质区域组织内伊文思蓝水平。结果 脑缺血组及干预组大鼠脑白质区域血管密度和伊文思蓝浓度均显著高于假手术组,白质纤维密度显著低于假手术组,干预组微血管密度、白质纤维密度及脑组织内伊文思蓝水平显著低于脑缺血组。结论 慢性低灌注诱导的血管生成可能导致血脑屏障通透性增加,但血管生成有助于减轻白质损伤,但这种保护作用大于血脑屏障通透性改变带来的不利影响。     

Cumulative white matter changes in the gerbil brain under chronic cerebral hypoperfusion

Summary An animal model of chronic brain hypoperfusion has been developed by applying coiled clips to the bilateral carotid artery of Mongorian gerbils. The brain tissue damage was neuropathologically studied after 1, 4, 8, and 12 weeks of hypoperfusion. The hippocampus, basal ganglia, and cerebral cortex of the chronically hypoperfused gerbil showed lesions with various severity which are probably due to ischemic episodes. In the cerebral white matter, however, two types of lesions were observed; one similar to those in the gray matter, and the other observed only in the white matter after more than an 8-week duration of brain hypoperfusion. The lesion specific to the white matter showed rarefaction and gliosis without locally associated ischemic changes. This type of the white matter lesion was never found in the gerbil brain before 8 weeks and, significantly, increased in number and size by 12 weeks post operation. The accumulation of the white matter lesions is characteristic in the gerbil with chronic hypoperfusion. The observed white matter-specific lesion resembles the histological changes in aged brain with cerebrovascular diseases.     

Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study

Activation of glial cells and white matter changes (rarefaction of the white matter) induced in the rat brain by permanent bilateral occlusion of the commom carotid arteries were immunohistochemically investigated up to 90 days. One day after ligation of the arteries, expression of the major histocompatibility complex (MHC) class I antigen in microglia increased in the white matter including the optic nerve, optic tract, corpus callosum, internal capsule, anterior commissure and traversing fiber bundles of the caudoputamen. After 3 days of occlusion, MHC class I antigen was still elevated and in addition MHC class II antigen and leukocyte common antigen were up-regulated in the microglia in these same regions. Astroglia, labeled with glial fibrillary acidic protein, increased in number in these regions after 7 days of occlusion. A few lymphocytes, labeled with CD4 or CD8 antibodies, were scattered in the neural parenchyma 1 h after occlusion. Activation of glial cells and infiltration of lymphocytes persisted after 90 days of occlusion in the white matter and the retinofugal pathway. However, cellular activation and infiltration in microinfarcts of the gray matter was less extensive and was substantially diminished 30 days after occlusion. The white matter changes were most intense in the optic nerve and optic tract, moderate in the medial part of the corpus callosum, internal capsule and anterior commissure, and slight in the fiber bundles of the caudoputamen. These results indicated that chronic cerebral hypoperfusion induced glial activation preferentially in the white matter. This activation seemed to be an early indicator of the subsequent changes in the white matter.     

Relationship between cholinergic dysfunction and discrimination learning disabilities in Wistar rats following chronic cerebral hypoperfusion

The effects of chronic hypoperfusion of cerebral blood flow (CBF) on central cholinergic indices and intellectual functions were investigated in rats. Male Wistar rats, aged 9 weeks, were anesthetized with pentobarbital, and the bilateral common carotid arteries were permanently ligated. Cortical CBF in the hypoperfused rats was markedly decreased at 6 weeks after the operation. In the hypoperfused group, cholinergic indices were changed to consist two phases after the operation, before (acute) and after (chronic) 6 weeks after the operation. At 6 weeks, choline acetyltransferase activity was restored to the sham-operated level compared with the changes in the frontal cortex and thalamus + midbrain at 3 weeks. On the other hand, the maximum number of muscarinic acetylcholine receptors was reduced in the frontal cortex, hippocampus and striatum at 6 weeks and thereafter remained at this low level. In discrimination learning task, the percentage of correct responses in the hypoperfused rats was generally reduced in contrast with that of the sham-operated rats, although the number of total responses were not changed. As a consequence, cholinergic dysfunctions correlate with discrimination learning disabilities in the hypoperfused rats. These findings suggest that the hypoperfused rat may be useful for the cerebrovascular type dementia model to clarify pathophysiology.     

Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice

Some lines of evidence have suggested that subcortical ischemic vascular dementia (SIVD) is a common form of vascular dementia (VaD), and that its pathological changes are the development of ischemic white matter (WM) lesions under chronic hypoperfusion and lacunes. Here, we have developed a novel mouse model of VaD with WM lesions, which was induced by right unilateral common carotid artery occlusion (rUCCAO). The mice subjected to rUCCAO exhibited chronic cerebral hypoperfusion in the cerebral hemisphere ipsilateral to rUCCAO monitored using a laser-Doppler flow meter (p<0.01), and significant WM damage in the corpus callosum (p<0.05) and deficits in object recognition test correlated with the damage of frontal-subcortical circuits (p<0.01). However, no differences in spontaneous alternation or spontaneous motor activity were observed. Furthermore, the levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), significantly increased (p<0.01), and those of anti-inflammatory cytokines, such as interleukin-4 (IL-4) and interleukin-10 (IL-10), significantly decreased in the ischemic brain (p<0.05). These results suggest that this model is a useful tool for investigating the associations among inflammatory reactions, cognitive impairment, and WM damage, which may help elucidating the pathomechanism of VaD, particularly SIVD.     

Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

Carnosine is a dipeptide that scavenges free radicals,inhibits inflammation in the central nervous system,and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions.Therefore,we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury.White matter damage was induced by right unilateral common carotid artery occlusion in mice.The animals were treated with 200,500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury.Then,37 days later,Klüver-Barrera staining,toluidine blue staining and immunofluorescence staining were performed.Carnosine(200,500 mg/kg) substantially reduced damage to the white matter in the corpus callosum,internal capsule and optic tract,and it rescued expression of myelin basic protein,and alleviated the loss of oligodendrocytes.However,carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses.These findings show that carnosine,at a particular dose range,protects against white matter damage caused by chronic cerebral ischemia in mice,likely by reducing oligodendroglial cell loss.     

Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain

Though cerebral white matter injury is a frequently described phenomenon in aging and dementia, the cause of white matter lesions has not been conclusively determined. Since the lesions are often associated with cerebrovascular risk factors, ischemia emerges as a potential condition for the development of white matter injury. In the present study, we induced experimental cerebral hypoperfusion by permanent, bilateral occlusion of the common carotid arteries of rats (n=6). A sham-operated group served as control (n=6). Thirteen weeks after the onset of occlusion, markers for astrocytes, microglia, and myelin were found to be labeled by means of immunocytochemistry in the corpus callosum, the internal capsule, and the optic tract. The ultrastructural integrity and oligodendrocyte density in the optic tract were investigated by electron microscopy. Quantitative analysis revealed that chronic cerebral hypoperfusion caused mild astrogliosis in the corpus callosum and the internal capsule, while astrocytic disintegration in the optic tract increased by 50%. Further, a ten-fold increase in microglial activation and a nearly doubled oligodendrocyte density were measured in the optic tract of the hypoperfused rats as compared with the controls. Finally, vacuolization and irregular myelin sheaths were observed at the ultrastructural level in the optic tract. In summary, the rat optic tract appears to be particularly vulnerable to ischemia, probably because of the rat brains angioarchitecture. Since the detected glial changes correspond with those reported in vascular and Alzheimer dementia, this model of cerebral hypoperfusion may serve to characterize the causal relationship between ischemia and white matter damage.     

Elevated leukocyte count in asymptomatic subjects is associated with a higher risk for cerebral white matter lesions

Objective

Cerebral white matter lesions (WMLs) are radiologic markers of small vessel disease in brain, and inflammatory processes were related to WMLs. We propose to determine if elevated leukocyte count was associated with a higher risk of WMLs.

Methods

1586 asymptomatic subjects who visited our hospital for a routine health check-up were enrolled. Leukocyte counts were measured and the presence of moderate to severe WMLs was determined by brain MRI.

Results

Thirty (1.9%) had moderate to severe WMLs, and a significant greater proportion (4.1%) of subjects in the highest leukocyte count quartile had moderate to severe WMLs. After adjusting by C-reactive protein, aspirin use and cardiovascular risk factors, the highest quartile of leukocyte count (≥6.7 × 10⁹/L) was significantly associated with moderate to severe WMLs compared with the lowest quartile [adjusted odds ratio, 4.03; 95% confidence interval, 1.05-15.5].

Conclusion

The authors report for the first time that an elevated leukocyte count is independently associated with moderate to severe WMLs.     

Intensity of chronic cerebral hypoperfusion determines white/gray matter injury and cognitive/motor dysfunction in mice

We sought to establish a mouse model of subcortical ischemic vascular dementia (SIVD) that develops predominant white matter (WM) injury and cognitive dysfunction induced by chronic cerebral hypoperfusion. Adult C57Bl/6 male (n = 48) mice were subjected to bilateral common carotid artery stenosis with external microcoils (inner diameters: 0.16 mm, left; 0.18 mm, right). Mice were categorized according to left-side cerebral blood flow (CBF) value on day 6 into those with severe cerebral hypoperfusion (SCH; n = 16, < 30% of preoperative CBF baseline value) or moderate cerebral hypoperfusion (MCH; n = 21, 30-50% of preoperative value). Another 15 mice were sham operated. Neurological dysfunction was evaluated by Morris water maze, rotating rod, and open field tests. Histopathological examination was performed on day 35 after surgery. MCH animals showed persistent hyperlocomotion with reduced anxiety and spatial reference memory dysfunction. Rarefaction and small necrotic lesions were predominantly confined to the WM, with reactive astrocytosis, microglial infiltration, axonal loss, and myelin disruption, and these changes were dominant on the left side. SCH animals had persistent hyperlocomotion and motor dysfunction, and their ischemic lesions extended from the WM to the hippocampus and cortex. In MCH animals, myelin basic protein and neurofilament fiber densities in the WM were correlated with the time spent in the correct area in the water maze probe trials. Our MCH mouse model with the development of several types of neurological dysfunction with high reproducibility would be useful for investigating the pathomechanisms of WM injury in human SIVD.     

Microbial lipopolysaccharide-induced inflammation contributes to cognitive impairment and white matter lesion progression in diet-induced obese mice with chronic cerebral hypoperfusion

Aims

White matter lesions (WMLs) are involved in the pathological processes leading to cognitive decline and dementia. We examined the mechanisms underlying the exacerbation of ischemia-induced cognitive impairment and WMLs by diet-induced obesity, including lipopolysaccharide (LPS)-triggered neuroinflammation via toll-like receptor (TLR) 4.

Methods

Wild-type (WT) and TLR4-knockout (KO) C57BL/6 mice were fed a high-fat diet (HFD) or low-fat diet (LFD), and subjected to bilateral carotid artery stenosis (BCAS). Diet groups were compared for changes in gut microbiota, intestinal permeability, systemic inflammation, neuroinflammation, WML severity, and cognitive dysfunction.

Results

In WT mice, HFD induced obesity and increased cognitive impairment and WML severity compared with LFD-fed mice following BCAS. HFD caused gut dysbiosis and increased intestinal permeability, and plasma LPS and pro-inflammatory cytokine concentrations. Furthermore, HFD-fed mice had higher LPS levels and higher neuroinflammatory status, including increased TLR4 expression, in WMLs. In TLR4-KO mice, HFD also caused obesity and gut dysbiosis but did not increase cognitive impairment or WML severity after BCAS. No difference was found between HFD- and LFD-fed KO mice for LPS levels or inflammatory status in either plasma or WMLs.

Conclusion

Inflammation triggered by LPS–TLR4 signaling may mediate obesity-associated exacerbation of cognitive impairment and WMLs from brain ischemia.     

Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat

Cerebrovascular white matter lesions represent an age-related neurodegenerative condition that appears as a hyperintense signal on magnetic resonance images. These lesions are frequently observed in aging, hypertension and cerebrovascular disease, and are responsible for cognitive decline and gait disorders in the elderly population. In humans, cerebrovascular white matter lesions are accompanied by apoptosis of oligodendroglia, and have been thought to be caused by chronic cerebral ischemia. In the present study, we tested whether chronic cerebral hypoperfusion induces white matter lesions and apoptosis of oligodendroglia in the rat. Doppler flow meter analysis revealed an immediate reduction of cerebral blood flow ranging from 30% to 40% of that before operation; this remained at 52–64% between 7 and 30 days after operation. Transferrin-immunoreactive oligodendroglia decreased in number and the myelin became degenerated in the medial corpus callosum at 7 days and thereafter. Using the TUNEL method, the number of cells showing DNA fragmentation increased three- to eightfold between 3 and 30 days post-surgery compared to sham-operated animals. Double labeling with TUNEL and immunohistochemistry for markers of either astroglia or oligodendroglia showed that DNA fragmentation occurred in both of these glia. Messenger RNA for caspase-3 increased approximately twofold versus the sham-operated rats between 1 and 30 days post-surgery. Immunohistochemistry revealed up-regulation of caspase-3 in the oligodendroglia of the white matter, and also in the astroglia and neurons of the gray matter. Molecules involved in apoptotic signaling such as TNF- and Bax were also up-regulated in glial cells. These results indicate that chronic cerebral hypoperfusion induces white matter degeneration in association with DNA fragmentation in oligodendroglia.     

Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion

White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Klüver-Barrera staining was significantly attenuated in the minocycline-treated group compared to saline-treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox-42 as a microglial marker, and matrix metalloproteinase (MMP)-2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co-expression of Ox-42 and MMP-2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation.     

The plasticity of posterior communicating artery influences on the outcome of white matter injury induced by chronic cerebral hypoperfusion in rats

Abstract

Objective: This study was performed to identify which factors are involved in the development of white matter lesions induced by chronic cerebral hypoperfusion in rats.

Methods: Male Wistar and Sprague–Dawley (SD) rats (250–270 g) were subjected to the permanent occlusion of bilateral common carotid arteries (BCCAO). The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry and the plasticity of the posterior communicating artery (PcomA) was visualized by transcardiac perfusion of latex solution. For the histological examination, Klüver–Barrera staining was used to evaluate white matter damage.

Results: When compared with SD rats, Wistar rats showed lower rCBF after BCCAO, as well as thinner PcomAs. Moreover, 21 days after BCCAO, Wistar rats showed marked vacuolation of white matter in the optic tract, whereas SD rats had an almost intact optic tract.

Discussion: These results suggest that the plasticity of the PcomA and the reduction of rCBF in Wistar rats are important factors in the development of BCCAO-induced white matter lesions.     

Erythropoietin reduces white matter damage in two-day-old rats exposed to hypoxic/ischemia injury

Objective: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model.

Methods: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery. Body weight, brain weight, brain water content, and expression of myelin basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris water-maze (MWM) test was used to assess neurological behavior from day 31 to 35 after HI insult.

Results: Body weights of BCAO + EPO group were greater than those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain weights of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05); at day 7 and 14 after HI, MBP of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3 after HI in BCAO + EPO-treated rats was lower than BCAO-treated animals (P < 0.05). The body weight, brain weight, brain water content, and MBP expression in BCAO + EPO-treated group were comparable to those in the sham-treated group. Spatial learning and memory of BCAO + EPO-treated rats was significantly improved over the BCAO-treated group and was comparable to the sham-operated animals.

Conclusion: EPO treatment could be a potential intervention in treating WMD for preterm infants.     

脑白质病变相关性轻度认知功能障碍患者神经心理学特征分析

目的观察脑白质病变(WML)对轻度认知功能损害(mild cognitive impairment,MCI)患者神经心理学的影响。方法 WML-MCI患者和健康对照者进行常规核磁共振及神经心理学检查,观察WML对MCI患者神经心理学的影响,并对其机制进行探讨。结果 WML-MCI组与对照组相比,高血压、糖尿病和冠心病比例明显增高;词语流畅性测验、积木测验和画钟测验评分均明显降低(P<0.05);而2组间MMSE、数字广度测验和词语延迟回忆测验评分无明显差异。结论 WML影响MCI患者的认知功能,主要表现为视空间及执行功能。血管危险因素是MCI发病的危险因素。     

反复前脑缺血大鼠脑白质区胶质纤维酸性蛋白表达变化

目的观察大鼠反复前脑缺血再灌注后不同脑白质区胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）表达的变化，探讨其规律，为对脑缺血后星形胶质细胞的进一步研究提供实验依据。方法反复夹闭大鼠双侧颈总动脉制备前脑缺血再灌注模型，免疫组化法检测脑缺血再灌注后1周、2周、4周胼胝体、内囊和脑室周围GFAP的表达。结果缺血再灌注后，不同部位各时间点GFAP的表达均高于假手术组水平；在胼胝体、内囊GFAP的表达在1周时增加，2周时持续上升，4周时更明显；而脑室周围则在1周时上升，2周时达高峰，4周时回落但仍高于1周时的水平。结论反复前脑缺血后白质区GFAP表达明显升高，但不同脑区变化的规律和幅度略有差异，说明不同脑区对缺血的敏感性不同，星形胶质细胞的反应性略有差异。