Bcl-2腺病毒/E1B 19kD相互作用蛋白3对弥漫性轴索损伤后少突胶质细胞凋亡的调控作用

目的 探讨Bcl-2腺病毒/E1B 19kD相互作用蛋白3(BNIP3)对大鼠弥漫性轴索损伤(DAI)后少突胶质细胞凋亡的调控作用.方法 77只SD雄性成年大鼠随机分为假手术组(11只)、DAI组(33只)及干预组(33只).参照Marmarou方法制做DAI模型,干预组大鼠在打击后立即给予脑室注射BNIP3抑制剂necrostatin-1(Nec-1,30 g/L,2 μl),检测Nec-1干预前后DAI大鼠BNIP3蛋白表达,少突胶质细胞凋亡以及髓鞘的组织病理学变化.结果 与假手术组相比,大鼠DAI损伤后脑干组织BNIP3表达上调,且与细胞凋亡成正相关;Nec-1干预有效降低DAI大鼠少突胶质细胞BNIP3蛋白表达,显著减少DAI大鼠少突胶质细胞凋亡的数目,提高DAI大鼠脑干髓鞘劳克坚牢蓝(LFB)染色平均吸光度和髓鞘碱性蛋白(MBP)表达,改善DAI大鼠脑干髓鞘的超微结构.结论 BNIP3参与DAI诱导的少突胶质细胞凋亡,抑制BNIP3可保护DAI大鼠少突胶质细胞和髓鞘.     

Olig对少突胶质细胞介导脱髓鞘大鼠髓鞘再生的影响

目的 探讨Olig在少突胶质细胞介导的脱髓鞘大鼠髓鞘再生中的作用。方法 40只健康Wistar大鼠,随机分成正常组、模型对照组、模型组、实验组,用形态学观察和免疫组织化学检测Olig1和Olig2的表达。结果 正常组Olig1位于少突胶质细胞的胞质,模型组胞核表达明显增多,实验组Oligl又重新转移至胞质;正常组Olig2表达位于胞核,模型组中有少量表达于胞质。 结论 在Olig1和Olig2同时缺失时,导致全脑不能形成少突胶质细胞,严重影响髓鞘的再生。     

电针对脊髓损伤后少突胶质细胞再髓鞘化的影响

目的：观察电针治疗对脊髓损伤后少突胶质细胞增生及新生轴突髓鞘再形成的影响。方法：选用成年大鼠,制作中度脊髓损伤模型,应用督脉电针治疗。电镜观察各组髓鞘和少突胶质细胞的超微结构变化;原位杂交显示髓磷脂碱性蛋白（myelin basic protein,MBP）的基因表达。结果：脊髓损伤后髓鞘明显肿胀,部分崩解;少突胶质细胞坏死溶解。1～2周后出现少量增生少突胶质细胞和厚薄不等的髓鞘。电针组髓鞘肿胀较轻,少突胶质细胞坏死少。1周后可见较多增生的少突胶质细胞和完整髓鞘。原位杂交显示电针组MBP基因表达明显高于损伤组,3d组最低,1周达高峰,此后逐渐下降。结论：脊髓损伤后电针治疗可有效防止神经纤维的溃变,促进少突胶质细胞增生和再生神经纤维髓鞘再形成。     

大鼠脊髓损伤后星形胶质细胞特异性表达Gc的研究

用免疫组织化学方法观察了脊髓的星形胶质细胞在损伤后出现的抗原性改变并对其改变的意义进行了探讨。实验选用Wistar大鼠 2 0只。实验组 10只 ,对脊髓 T1 0 节段进行完全横断 ;对照组 10只 ,只进行 T1 0 椎板切除术 ,不损伤脊髓。在术后第 1、3、5、7、14 d分别对 2 0只大鼠灌流固定 ,并取出 3 cm长手术段脊髓。用 anti-Galactocerebrosides( anti-Gc)和 anti-glial fibrillaryacidic protein( anti-GFAP)抗体对脊髓进行标记。结果表明 :脊髓损伤后第 7d,增生肥大的星形胶质细胞可以同时被 anti-GF AP和 anti-Gc标记 (荧光双标 )。此抗原表型改变至术后 14 d依然显现。被双标的星形胶质细胞在形态上与成熟的正常胶质细胞基本相同 ,而少突胶质细胞只为 anti-Gc单独标记。对照组脊髓星形胶质细胞和少突胶质细胞只为 anti-GFAP、anti-Gc分别标记。本实验结果提示 :大鼠脊髓受损后 ,星形胶质细胞出现 GFAP和 Gc二种抗原表型。此结果首次表明成熟哺乳动物脊髓损伤后星形胶质细胞也可出现类似少突胶质细胞特异性抗原抗体改变。这可能是星形胶质细胞对脊髓创伤的一种特异性反应。这种变化可为探索脊髓损伤区域微环境的变化对脊髓损伤修复的影响提供新的线索     

过表达Olig2的少突胶质前体细胞在缺血缺氧脑白质损伤新生大鼠脑内的分化

目的:观察过表达特异性转录因子Olig2的少突胶质前体细胞(oligodendrocyte precursor cells,OPCs)移植在缺血缺氧(hypoxia-ischemia,HI)脑白质损伤新生大鼠脑内的分化情况。方法:用绿色荧光蛋白(green fluorescent protein,GFP)标记的过表达Olig2的慢病毒感染原代分离纯化的大鼠大脑皮层OPCs,GFP阳性细胞计数测其感染率。将过表达Olig2的OPCs(Olig2组)或阴性对照病毒感染的OPCs(Vector组)脑立体定位注射到造模后7 d的HI模型大鼠胼胝体膝部,移植后2周,冰冻切片行免疫荧光染色观察OPCs的存活和分化情况。结果:Olig2-GV218病毒感染OPCs细胞48 h,荧光显微镜检测显示85%左右的OPCs细胞表达GFP;移植后2周,caspase-3荧光染色表明移植后绝大部分细胞存活,Vector组和Olig2组之间无统计学差异(P0.05);GFAP/GFP双阳性细胞在两组之间也无显著差异(P0.05);而Olig2组MBP/GFP双阳性细胞的荧光密度显著高于Vector组(P0.05)。结论:过表达Olig2可促进移植OPCs向少突胶质细胞分化。     

NG2胶质细胞在中枢神经系统病变中作用的研究进展

NG2胶质细胞是中枢神经系统中除星形胶质细胞、小胶质细胞和少突胶质细胞外的第四类胶质细胞,均匀地分布在整个脑区。当中枢神经系统发生损伤时,NG2胶质细胞能通过改变其细胞形态、增殖和分化对多种损伤类型作出反应。弄清NG2胶质细胞对不同损伤的反应机制,有助于更好地发挥其在损伤修复和髓鞘再生中的作用。本文着重讨论了NG2胶质细胞在几种损伤类型中的反应。     

新生幼鼠缺血缺氧性脑损伤后少突胶质细胞及髓鞘超微结构的变化

目的:探索3日龄幼鼠单侧颈总动脉结扎联合缺氧造成脑白质损伤后少突胶质细胞及髓鞘超微结构的变化。方法:将3日龄未成熟SD新生大鼠随机分为对照组和实验组。实验组大鼠结扎右侧颈总动脉,置8%O2和92%N2混合气体的缺氧装置2h后,取出返笼饲养。对照组仅游离右侧颈总动脉,并未结扎及缺氧实验。术后28d透射电镜观察胼胝体少突胶质细胞及髓鞘超微结构。结果:对照组大鼠少突胶质细胞染色质分布均匀,细胞器结构完整;髓鞘厚度及数目均正常;实验组大鼠部分少突胶质细胞核固缩、核破碎,细胞器广泛缺失;与对照组相比髓鞘厚度变薄,数目明显减少。结论:3日龄幼鼠脑缺血缺氧28d后,脑白质少突胶质细胞的超微结构发生了坏死性病理改变,髓鞘形成能力减弱,髓鞘化轴突的数目减少。     

墨西哥钝口螈脊髓全切后胶质细胞的变化

背景：墨西哥钝口螈脊髓切断可以再生,再生过程伴随胶质细胞数目及分布的改变,研究墨西哥钝口螈脊髓全切后胶质细胞的变化,对进一步探讨其脊髓切断再生机制有重要意义。 目的：观察墨西哥钝口螈脊髓全切后小胶质细胞、星形胶质细胞及少突胶质细胞的变化。 方法：选用成年墨西哥钝口螈,分为脊髓全切组和对照组,利用免疫组织化学法观察脊髓全切后1,3和10 d的损伤脊髓及周围区cd11b标记的小胶质细胞、胶质细胞原纤维酸性蛋白标记的星形胶质细胞及髓鞘碱性蛋白标记的少突胶质细胞的变化。 结果与结论：脊髓全切后短期内cd11b染色阴性;脊髓损伤后胶质细胞原纤维酸性蛋白及髓鞘碱性蛋白阳性细胞染色强度,1 d组阳性细胞染色强度与对照组比较无显著差异,3及10 d组阳性细胞染色强度较对照组低。墨西哥钝口螈小胶质细胞染色阴性,可能存在不同于哺乳动物的标记蛋白;脊髓全切后3及10 d在损伤脊髓及周围区的胶质细胞原纤维酸性蛋白及髓鞘碱性蛋白阳性细胞染色强度较对照组低,提示钝口螈脊髓急性损伤早期未见星形胶质细胞及少突胶质细胞增生,无胶质瘢痕形成。     

BMP-4在视网膜与视神经中的分布及对少突胶质前体细胞分化的影响

目的:研究骨形态发生蛋白4(bone morphogenetic protein4,BMP-4)在视网膜与视神经上的表达情况及其对少突胶质前体细胞(oligodendrocyte precursor cells,OPCs)分化的影响,进一步探讨视神经乳头处无髓鞘形成的原因。方法:取生后7d SD大鼠视神经,用免疫组织化学方法研究BMP-4的表达情况。采用恒温振荡法和差速贴壁法分离纯化新生SD大鼠OPCs。用BMP-4诱导OPCs分化,通过免疫细胞化学方法研究OPCs的分化方向。通过Western Blot方法研究BMP-4浓度与OPCs细胞体系内Olig2蛋白表达水平之间的相互关系。结果:(1)在发育过程中,BMP-4仅选择性表达在视神经乳头处;(2)成功纯化的OPCs在PDGF和bFGF撤除后自发分化为少突胶质细胞;(3)OPCs经BMP-4诱导后向II型星形胶质细胞分化;(4)OPCs内Olig2蛋白的表达量随着BMP-4浓度的逐渐增高而逐渐降低。结论:在视神经乳头表达的BMP-4蛋白有可能作用于迁移至此处的OPCs,通过激活相关信号途径以下调OPCs内Olig2蛋白的表达水平,抑制OPCs向少突胶质细胞方向分化,从而抑制视神经乳头髓鞘形成。     

大鼠脊髓硫酸软骨素蛋白多糖4细胞的生后发育特征

 目的 研究大鼠脊髓中硫酸软骨素蛋白多糖4（NG2）细胞生后发育特征。方法 采用免疫组织化学及Western blot,观察生后不同发育阶段的脊髓中NG2细胞形态变化。结果 免疫组织化学染色显示,在大鼠生后各发育阶段的脊髓内均有NG2细胞表达;脊髓内NG2细胞胞体逐渐增大,其形态由圆形或卵圆形变为不规则形,突起数目和长度随之增加。与同时期大脑皮层的NG2细胞形态比较,脊髓内的NG2细胞胞体要大,突起短而少。Western blot显示,P1d,脊髓内NG2表达水平最高, P7d开始下降,P21d最低,P60d回升。结论 在大鼠不同发育阶段的脊髓内,NG2细胞形态数量不同, P7d到P21d是脊髓内神经纤维髓鞘主要形成期;脊髓内NG2细胞可能处于少突胶质细胞系发育的早期阶段。     

Regional difference of reactive astrogliosis following traumatic brain injury revealed by hGFAP-GFP transgenic mice

Reactive astrocytes greatly influence the wound healing and neuronal regeneration processes following brain injury. However, the origin and fate of reactive astrocytes appear to be different depending on the type, severity and duration of brain injury. Using the cryogenic traumatic brain injury model, here we comprehensively addressed the regional differences of reactive astrocytes in the injured cortex. In the proximal region of injury site, NG2-expressing and cytoplasmic Olig2-labeled cells were densely localized 3 days after the injury. Next to this proximal layer, most of reactive astrocytes did not express NG2 but exhibited radial glia-like shape with elongated processes. Accordingly, they expressed the progenitor or radial glial markers, such as vimentin, brain lipid binding protein (BLBP) and the green fluorescent protein (GFP) under the control of the human GFAP (hGFAP) promoter. However, only few glial fibrillary acidic protein (GFAP) expressing astrocytes were found in this layer. Distal to the injury site, most of astrocytes strongly expressed GFAP with hypertonic morphology. At day 15 after injury, all layers expressing GFAP and other marker expressions disappeared, indicating the termination of reactive astrogliosis. Taken together, our data suggest that reactive astrogliosis occurs in a regionally segregated manner in the early phase of brain injury.     

A functional role for EGFR signaling in myelination and remyelination

Cellular strategies for oligodendrocyte regeneration and remyelination involve characterizing endogenous neural progenitors that are capable of generating oligodendrocytes during normal development and after demyelination, and identifying the molecular signals that enhance oligodendrogenesis from these progenitors. Using both gain- and loss-of-function approaches, we explored the role of epidermal growth factor receptor (EGFR) signaling in adult myelin repair and in oligodendrogenesis. We show that 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter-driven overexpression of human EGFR (hEGFR) accelerated remyelination and functional recovery following focal demyelination of mouse corpus callosum. Lesion repopulation by Cspg4+ (also known as NG2) Ascl1+ (also known as Mash1) Olig2+ progenitors and functional remyelination were accelerated in CNP-hEGFR mice compared with wild-type mice. EGFR overexpression in subventricular zone (SVZ) and corpus callosum during early postnatal development also expanded this NG2+Mash1+Olig2+ progenitor population and promoted SVZ-to-lesion migration, enhancing oligodendrocyte generation and axonal myelination. Analysis of hypomorphic EGFR-mutant mice confirmed that EGFR signaling regulates oligodendrogenesis and remyelination by NG2+Mash1+Olig2+ progenitors. EGFR targeting holds promise for enhancing oligodendrocyte regeneration and myelin repair.     

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT/β‐catenin signal pathway. Sprague Dawley (SD) rats aged 1 day were intraperitoneally injected with lipopolysaccharide (LPS) (1 mg/kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7 days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2⁺ oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28‐day septic rats. The number of PLP⁺ and MBP⁺ cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g‐ratios were higher. This was coupled with an increase in number of NG2⁺ cells and decreased number of CC1⁺ cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7 days could reverse the above‐mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT/β‐catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a in vitro. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT/β‐catenin signaling pathway, which would contribute ultimately to axonal hypomyelination.     

Increase of NG2-positive cells associated with radial glia following traumatic spinal cord injury in adult rats

In the CSN including the spinal cord, NG2 proteoglycan is a marker of oligodendrocyte progenitors. To elucidate the dynamics of the endogenous neural stem (progenitor) cells in adult rats with spinal cord injury (SCI), we examined an immunohistochemical analysis of NG2, GFAP, and 3CB2, a specific marker of radial glia (RG). SD rats were divided into a SCI group (n = 25) and a sham-operated group (n = 5). In the injury group, laminectomy was performed at Th11–12 and contusive compression injury was created by applying a weight of 30 g for 10 min. Rats were sacrificed at 24 h, and 1, 4, 8 and 12 weeks post-injury. Frozen 20-μ m sections of tissue 5 and 10 mm rostral and caudal to the epicenter of injury were prepared. Immunohistochemistry was performed using antibodies against NG2, GFAP and 3CB2. At 4 weeks after injury, NG2-positive glial cells arose from below the pial surface as bipolar cells with processes extending throughout the entire white matter. NG2 expression peaked at 4 weeks after injury, showing a 7-fold increase compared to the 24 h after injury. The NG2-positive cells with processes which increased in the white matter of the spinal cord were GFAP-positive and also co-localized with 3CB2 antigen. The pattern of NG2 expression of these cells was temporally and spatially different from the pattern of NG2 expression that accumulated around the hemorrhagic and necrotic epicenter. These results suggest that NG2 positive cells which derived from subpial layer, may have some lineage to RG after SCI in adult rodents. The first and second authors contributed equally to this work.     

Effects of Lipopolysaccharide on Oligodendrocyte Differentiation at Different Developmental Stages: an In Vitro Study

BackgroundLipopolysaccharide (LPS) exerts cytotoxic effects on brain cells, especially on those belonging to the oligodendrocyte lineage, in preterm infants. The susceptibility of oligodendrocyte lineage cells to LPS-induced inflammation is dependent on the developmental stage. This study aimed to investigate the effect of LPS on oligodendrocyte lineage cells at different developmental stages in a microglial cell and oligodendrocyte co-culture model.MethodsThe primary cultures of oligodendrocytes and microglia cells were prepared from the forebrains of 2-day-old Sprague–Dawley rats. The oligodendrocyte progenitor cells (OPCs) co-cultured with microglial cells were treated with 0 (control), 0.01, 0.1, and 1 µg/mL LPS at the D3 stage to determine the dose of LPS that impairs oligodendrocyte differentiation. The co-culture was treated with 0.01 µg/mL LPS, which was the lowest dose that did not impair oligodendrocyte differentiation, at the developmental stages D1 (early LPS group), D3 (late LPS group), or D1 and D3 (double LPS group). On day 7 of differentiation, oligodendrocytes were subjected to neural glial antigen 2 (NG2) and myelin basic protein (MBP) immunostaining to examine the number of OPCs and mature oligodendrocytes, respectively.ResultsLPS dose-dependently decreased the proportion of mature oligodendrocytes (MBP+ cells) relative to the total number of cells. The number of MBP+ cells in the early LPS group was significantly lower than that in the late LPS group. Compared with those in the control group, the MBP+ cell numbers were significantly lower and the NG2+ cell numbers were significantly higher in the double LPS group, which exhibited impaired oligodendrocyte lineage cell development, on day 7 of differentiation.ConclusionRepetitive LPS stimulation during development significantly inhibited brain cell development by impairing oligodendrocyte differentiation. In contrast, brain cell development was not affected in the late LPS group. These findings suggest that inflammation at the early developmental stage of oligodendrocytes increases the susceptibility of the preterm brain to inflammation-induced injury.     

The effect of varying impact energy on diffuse axonal injury in the rat brain: a preliminary study

Diffuse axonal injury (DAI) is seen as widespread damage in the white matter of brain characterized by morphological changes to axons throughout the brain and brain stem. The current study attempted to investigate the effect of increasing impact energy on the presence and severity of DAI in corpus callosum (CC). DAI was induced in adult male Sprague-Dawley rats using an injury model adapted from Marmarou et al. in 1994. A 450-g cylindrical brass weight was dropped from three different heights (2.0 m, 1.5 m and 1.0 m) on to a metal helmet affixed to the skull of the rats. In the sham group, rats underwent a surgical procedure with no impact. After a 24-h survival period the animals were transcardially perfused. The brain was removed and the cerebral hemispheres were sectioned with a vibrotome and stained by silver impregnation technique. The CC of all the impacted rats showed DAI in the form of beaded axons, retraction balls and vacuole-like enlargements. The axonal injury was most severe in the 2-m group, while mildest in the 1-m group. In the sham group, axons appeared to be normal. This study demonstrates evidence of graded DAI depending on the impact energy. Such data is useful for mathematical modeling of axonal injury in rat brain using the same impact parameters and potential determination of injury thresholds for neural trauma. Electronic Publication     

The injury response of oligodendrocyte precursor cells is induced by platelets, macrophages and inflammation-associated cytokines

Oligodendrocyte precursor cells recognized with the NG2 antibody respond rapidly to CNS injuries with hypertrophy and upregulation of the NG2 chondroitin sulfate proteoglycan within 24 h. These cells participate in glial scar formation, remaining around the injury site for several weeks. After injury, reactive oligodendrocyte precursor cells increase their production of several chondroitin sulfate proteoglycans, including NG2: this cell type thus represents a component of the inhibitory environment that prevents regeneration of axons in the injured CNS. This study analyzes factors that activate oligodendrocyte precursor cells. Both microglia and astrocytes become reactive around motor neurons following peripheral nerve lesions. We show that oligodendrocyte precursor cells do not hypertrophy or increase NG2 levels after these lesions. Those lesions that cause an oligodendrocyte precursor cell reaction generally open the blood-brain barrier. We therefore opened the blood-brain barrier with microinjections of vascular endothelial growth factor or lipopolysaccharide to the rat and mouse brain, and examined oligodendrocyte precursor cell reactivity after 24 h. Both treatments led to increases in NG2 and hypertrophy of oligodendrocyte precursor cells. Of directly injected blood components serum and thrombin were without effect, while platelets and macrophages activated oligodendrocyte precursor cells. We tested the effects of a range of injury-related cytokines, of which tumor necrosis factor alpha; interleukin-1; transforming growth factor beta; interferon gamma had effects on oligodendrocyte precursor cells. Oligodendrocyte precursor cell chemokines, and mitogens did not increase NG2 levels.     

Exogenous l-DOPA induce no dopamine immuno-reactivity in striatal astroglias and microglias of adult rats with extensive nigro-striatal dopaminergic denervation

The aim of this study was to determine whether striatal glial cells of adult rats with extensive nigro-striatal dopaminergic denervation are induced to contain dopamine by injection of exogenous l-DOPA. At 2 weeks after injection of 6-hydroxydopamine into the medial forebrain bundle of rats, immuno-reactivity of glial cells was detected with antibodies against glial fibrillary acidic protein (GFAP) or ionized calcium binding adapter molecule 1 (Iba1) in the intact and lesioned striatum. Double-labeling immunofluorescence method was secondly performed. In the lesioned striatum, immuno-reactivity of GFAP was significantly increased, whereas immuno-reactivity of Iba1 was significantly increased except for ventral portion. Exogenous l-DOPA induced DA immuno-reactivity in the striatum, which was independently detected from GFAP immuno-positive astroglial cells or Iba1 immuno-positive microglial cells in the intact side as well as in the lesioned side. These findings suggest that the proliferation of glial cells in the striatum is the response to the loss of dopaminergic terminals but the glial cells do not compensate for the lost dopaminergic terminals.     

脊髓损伤后硫酸软骨素蛋白多糖及GFAP表达的变化

目的探讨脊髓损伤后NG2、Neurocan、GFAP表达的变化。方法将32只雌性SD大鼠随机分为空白对照组和模型组。模型组采用脊髓横切法制作脊髓损伤模型,空白对照组仅切除T10全椎板及T9、T11部分椎板,对脊髓未作任何处理。分别在大鼠脊髓损伤制作后3、7、14及28 d时取材,利用免疫组织化学染色方法检测NG2、Neurocan、GFAP的表达情况。结果模型组脊髓损伤后3 d时NG2的表达出现明显升高,7 d时NG2的表达达到最高点,14 d及28 d时NG2仍然维持在较高水平,但与7 d时的表达相比有下降,空白对照组NG2各时间点均呈低表达。模型组脊髓损伤后7 d时Neurocan的表达显著增加,于14 d时达到最高点,从14 d开始Neurocan的表达开始逐步下降,空白对照组Neurocan各时间点均呈低表达。模型组脊髓损伤后3 d时GFAP的表达明显升高,14 d时GFAP的表达达到顶点,28 d时损伤部位GFAP的表达均较空白对照组明显升高,两组比较差异有统计学意义(均P<0.05)。结论脊髓损伤后NG2、Neurocan、GFAP表达升高,可能是脊髓损伤后抑制轴突再生的因素之一。     

Involvement of the Subplate Zone in Preterm Infants with Periventricular White Matter Injury

Studies of periventricular white matter injury (PWMI) in preterm infants suggest the involvement of the transient cortical subplate zone. We studied the cortical wall of non‐cystic and cystic PWMI cases and controls. Non‐cystic PWMI corresponded to diffuse white matter lesions, the predominant injury currently detected by imaging. Glial cell populations were analyzed in post‐mortem human frontal lobes from very preterm [24–29 postconceptional weeks (pcw)] and preterm infants (30–34 pcw) using immunohistochemistry for glial fibrillary acidic protein (GFAP), monocarboxylate transporter 1 (MCT1), ionized calcium‐binding adapter molecule 1 (Iba1), CD68 and oligodendrocyte lineage (Olig2). Glial activation extended into the subplate in non‐cystic PWMI but was restricted to the white matter in cystic PWMI. Two major age‐related and laminar differences were observed in non‐cystic PWMI: in very preterm cases, activated microglial cells were increased and extended into the subplate adjacent to the lesion, whereas in preterm cases, an astroglial reaction was seen not only in the subplate but throughout the cortical plate. There were no differences in Olig2‐positive pre‐oligodendrocytes in the subplate in PWMI cases compared with controls. The involvement of gliosis in the deep subplate supports the concept of the complex cellular vulnerability of the subplate zone during the preterm period and may explain widespread changes in magnetic resonance signal intensity in early PWMI.