光化学反应法建立拟血管性痴呆大鼠模型的改进

目的 建立拟血管性痴呆大鼠模型，以期为血管性痴呆病理研究和防治药物开发提供可靠实用的动物模型。方法 利用光化学反应诱导血栓形成的原理，短时间内造成大鼠脑皮质完全性局灶性梗死，7d后测定其水迷宫学习记忆与空间探索能力；电镜观察神经细胞、突触形态结构；免疫组化染色观察神经细胞Fas表达。结果 模型组大鼠学习记忆与空间探索能力下降，与对照组和生理盐水组比较差异有显著性（分别为P〈0．05．P〈0．01）；电镜下，模型组大鼠出现神经细胞核内染色质固缩、边聚、断裂等凋亡征象，突触数量减少且结构破坏，神经髓鞘水肿；模型组大鼠神经细胞Fas表达与其他两组比较显著增多（P〈0．01）。结论 光化学反应法建立的拟血管性痴呆大鼠模型在神经细胞超微结构、FAS免疫组化染色等方面具有血管性痴呆部分临床病理特征。     

芬戈莫德在脑白质缺血损伤中的神经保护研究

目的以临床常见的缺血性脑白质损伤为研究切入点,研究S1P受体激动剂芬戈莫德(FTY720)在小鼠低灌注脑白质损伤后对髓鞘脱失、认知功能障碍的影响,并探讨在小鼠低灌注脑白质损伤后FTY720对小胶质细胞活化、吞噬的影响,FTY720对少突胶质细胞存活、增殖、分化的影响。方法建立小鼠双侧颈总动脉狭窄(BCAS)模型,通过8臂迷宫行为学测试方法探究FTY720对小鼠造模后认知功能的影响; LFB染色观察FTY720对小鼠造模后髓鞘的影响;共聚焦显微镜观察FTY720干预后小胶质细胞在小鼠低灌注损伤后一个月的变化。结果成功建立小鼠低灌注白质损伤模型(BCAS)。FTY720干预后,白质区域损伤情况明显好于空白对照组。FTY720在低灌注后抑制小胶质细胞活化、吞噬,减轻小鼠的认知功能损害。结论慢性低灌注可以造成选择性的脑白质损伤以及认知功能障碍; FTY720在低灌注后抑制小胶质细胞活化、吞噬,减少髓鞘脱失,改善缺血性脑白质损伤,减轻小鼠的认知功能损害。因此FTY720有望成为缺血性脑白质损伤治疗的潜在靶点。     

高血压大鼠脑内小血管改变及其继发损伤的研究

目的通过对比研究自发高血压大鼠(SHR)与非高血压W istar大鼠(NHR)脑内血管及其继发神经元、髓鞘病理改变,阐述高血压病对脑血管及中枢神经系统的影响。方法将10只SHR和10只W istar大鼠分为单纯高血压组及非高血压对照组。M orris水迷宫观察大鼠空间记忆能力,HE染色观察大鼠脑内小血管的形态、数量,额叶、颞叶、海马、丘脑神经元细胞的改变,LFB染色观察脑室周围髓鞘改变,并结合图像分析、统计学方法综合分析行为学、脑内小血管及神经元细胞、脑室周围深部白质髓鞘改变的关系。结果单纯高血压组记忆功能较非高血压对照组明显下降(P<0.05);单纯高血压组与非高血压对照组比较,无论皮层还是皮层下小动脉直径明显变小(P<0.05)。单纯高血压组神经元及髓鞘较非高血压对照组明显脱失(P<0.05)。结论长期高血压可造成脑内小动脉狭窄;狭窄的小动脉可导致神经元、髓鞘脱失,神经功能受损;实验条件下,神经元、髓鞘脱失可致血管性痴呆。     

中成药天智颗粒对血管性痴呆大鼠脑内神经细胞增殖的影响

目的观察中成药天智颗粒对血管性痴呆大鼠学习记忆能力和神经前体细胞与星形胶质细胞增殖水平的影响。方法老年雄性SD大鼠192只,随机分为治疗组、模型组、假手术组和正常对照组,每组48只。治疗组、模型组采用双侧颈总动脉结扎方法建立血管性痴呆大鼠模型,于造模60d后治疗组大鼠应用天智颗粒5g/(kg·d)治疗30d。采用三等分Y型电迷宫测试各组大鼠的学习记忆能力,应用免疫组织化学尿嘧啶脱氧核苷(BrdU)和胶质纤维酸性蛋白(GFAP)染色方法标记并观察神经细胞增殖变化,以比较各组大鼠学习记忆能力和神经细胞增殖的变化规律和差异。结果与正常对照组相比,假手术组大鼠的学习记忆能力和免疫组织化学检测结果无明显变化。经天智颗粒治疗30d后,治疗组大鼠学习记忆能力明显改善,与模型组相比差异有统计学意义(P<0.05),BrdU阳性细胞显著增加(P<0.05),而星形胶质细胞明显减少(P<0.05);但与正常对照组相比,其学习记忆能力、BrdU阳性细胞和星形胶质细胞数量仍未恢复至正常水平(P<0.05)。结论天智颗粒可通过促进神经前体细胞的增殖而抑制星形胶质细胞的增殖,从而改善血管性痴呆大鼠的学习记忆能力。     

高血压大鼠脑白质病变中髓鞘和轴索改变

目的探究高血压大鼠脑白质病变中轴索微结构的变化。方法 18只雄性Sprague-Dawley大鼠,随机分为假手术组(n=9)与手术组(n=9),手术组先行双肾双夹术制作易卒中型肾血管性高血压大鼠模型,12周后间隔1 d先后夹闭双侧颈总动脉。颈总动脉夹闭术后12周对大鼠进行水迷宫试验评价大鼠是否存在认知功能受损,组织病理学评价小血管病理学改变、脑白质病变、胶质细胞改变及轴索微结构的变化。结果水迷宫实验:手术组的逃避潜伏期较假手术组明显升高,穿越平台次数较假手术组明显降低,差异具有统计学意义(P0.05)。手术组大鼠存在小动脉内膜增厚、管腔狭窄;手术组较假手术组有明显的脑白质病变,且伴有少突胶质细胞减少;手术组病变部位Caspr表达明显减少,病变周围髓鞘正常区域出现郎飞结长度增加、结侧区长度增加及直径增粗。结论脑白质病变过程同时存在轴索和髓鞘的损伤。     

慢性前脑缺血致痴呆大鼠皮质及皮质下白质区病理学变化的对比研究

目的对比研究慢性前脑缺血致血管性痴呆(VD)大鼠额叶、颞叶皮质、海马及皮质下白质区的病理学变化，探讨血管性痴呆发病的病理基础。方法采用双侧颈总动脉永久结扎方法制备慢性前脑缺血致VD大鼠动物模型；通过常规HE及LFB染色，对比观察缺血后不同时间点大鼠额、颞叶皮质、海马区及皮质下白质的形态学改变；应用HPIAS-1000高清晰彩色病理图文分析系统进行图像分析．检测皮质下白质神经纤维脱失情况。结果HE染色结果显示：缺血1个月时额、颞叶皮质及海马区以锥体细胞缺血的改变为主，逐渐转变为锥体细胞凝固性坏死、变性、脱失及星形胶质细胞增生，少数大鼠额叶出现梗死灶；缺血1个月起实验组大鼠皮质下白质神经纤维疏松、断裂、脱失，且有随缺血时间延长而逐渐加重的倾向；图像分析显示缺血1个月实验组大鼠脑白质神经纤维脱失，出现囊泡样改变并逐渐增重。结论进行性的额、颞叶皮质、海马神经元退变以及皮质下白质损害是VD的病理基础，且白质区的损害要早于皮质。     

脑白质损害新生大鼠的电镜超微结构观察

目的：应用Han方法建立脑白质损害（WMD）新生大鼠模型,电镜观察大鼠脑内髓鞘成熟度及突触超微结构改变。方法：2日龄新生SD大鼠39只,随机分为对照组(n=12)、假手术组(n=12)及WMD组(n=15)。WMD组大鼠在乙醚麻醉下行右颈总动脉结扎术,术后吸含6%氧气的氮氧混合气4h,制作新生大鼠WMD模型。各组均正常饲养至1月龄时经灌注固定后行电镜检查,同时行HE染色观察。 结果：电镜观察可见WMD组患侧海马CA1区胶质细胞受损及髓鞘形成延迟。WMD组大鼠海马CA1区突触活性区长度、突触间隙宽度、突触后致密物厚度及突触界面曲率与对照组及假手术组无显著性差异（P>0.05）;HE染色可见实验组白质疏松。结论 从超微结构方面观察,此方法对新生大鼠脑白质损害特异性高,突触损害轻微,模型效果可靠。     

CX3CR1对缺血性白质的损伤作用

目的明确CX3CR1在缺血性白质中的分布与表达及与缺血性白质损伤的关系。方法将150只成年雄性Wistar大鼠随机分为正常组、假手术组及缺血组,采用双侧颈总动脉永久结扎法制备缺血性白质损伤模型,造模28 d后Morris水迷宫观察学习记忆功能,同时于术后1 d、3 d、7 d、14 d、28 d观察胼胝体、内囊及视神经的病理学变化和CX3CR1表达量的变化。结果 (1)造模后28 d,逃避潜伏期、探索路径长度及跨越平台次数缺血组较正常组和假手术组明显增加,有显著性差异(P0.01);(2)随着缺血时间的延长,Luxol Fast Blue(LFB)染色可见髓鞘崩解范围扩大,分层明显,部分髓鞘空泡状;CX3CR1表达量逐渐增加,与CD11b标记的小胶质细胞数目逐渐增多相一致且高于正常组和假手术组。结论 CX3CR1通过介导小胶质细胞的变化对缺血性白质产生损伤,进而影响空间学习记忆功能。     

海马锥体细胞的变化对血管性痴呆大鼠学习记忆能力的影响

目的研究海马锥体细胞的变化对血管性痴呆大鼠学习记忆能力的影响。方法将大鼠随机分成手术组及对照组,手术组制作血管性痴呆大鼠模型,30d后用Morris水迷宫检测两组大鼠学习记忆能力及HE染色检测海马锥体细胞数目的变化。结果手术组大鼠学习记忆能力明显下降,海马锥体细胞数目较对照组明显减少。结论血管性痴呆大鼠海马锥体细胞减少,学习记忆能力下降。     

康复训练对血管性痴呆大鼠认知功能障碍的影响及其分子机制

目的探讨康复训练对血管性痴呆大鼠空间学习记忆能力的改善作用,并从分子学角度探讨其机制。方法选择Wistar雄性大鼠25只,随机分为正常对照组(5只)、血管性痴呆组(10只)和康复训练组(10只)。采用双侧颈总动脉阻断法制作血管性痴呆大鼠模型,康复训练组大鼠于手术后2d开始进行康复训练;用Westernblotting方法测定大鼠海马组织中N-甲基-D-天冬氨酸受体1含量,用长时程增强及Morris水迷宫试验评价大鼠空间学习记忆能力。结果Morris水迷宫试验显示,血管性痴呆组大鼠水迷宫隐匿平台逃避潜伏期明显延长,经康复训练后学习记忆能力有所改善,但与正常对照组相比差异仍有统计学意义(P<0.05)。发生血管性痴呆后,大鼠海马组织中N-甲基-D-天冬氨酸受体1含量明显降低,康复训练使其含量较训练前明显升高,但仍未能达到正常对照组水平(P<0.05);血管性痴呆大鼠的长时程增强诱导功能亦明显受到抑制,康复训练后虽明显改善但未恢复至正常水平(P<0.05)。结论康复训练可提高大鼠空间学习记忆能力,促进长时程增强的形成,其分子机制可能与海马组织中N-甲基-D-天冬氨酸受体1表达水平的增高有关。     

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.     

脑缺血再灌注后少突胶质细胞转录因子Olig1、轴突生长抑制因子Nogo-A基因表达与白质损伤

目的 检测少突胶质细胞转录因子Olig1、轴突生长抑制因子Nogo-A在大鼠脑缺血再灌注后不同时间点基因表达的变化规律,观察白质损伤的病理变化,探讨两者之间的关系.方法 利用线栓法制备大鼠大脑中动脉缺血(middle cerebral artery occlusion,MCAO)再灌注模型,实时定量PCR方法(relative quantification PCR,RQ-PCR)检测各时间点Olig1、Nogo-A在大脑损伤白质区的基因表达,髓鞘快蓝-高碘酸雪夫(LFB-PAS)染色法标记大脑神经髓鞘,Bielschowsky银染法标记大脑神经轴突,并计算缺血侧与健侧髓鞘染色的积分吸光度(Ias)比值以代表白质受损程度.结果 (1)Olig1:Olig1在缺血再灌注不同时间点,在大脑白质区的基因表达量不同.缺血再灌注6 h Olig1表达量减低至假手术组的83%(与假手术组相比,q=2.074,P=0.042),7 d时表达量降至最低,14 d时恢复至基础水平,21 d时表达最升高至假手术组的1.52倍(与假手术组相比,q=6.362,P＜0.01,差异具有统计学意义).Nogo-A:Nogo-A在缺血再灌注不同时间点,在大脑白质区的基因表达量不同.Nogo-A 基因表达在缺血再灌注1 d时开始减低,表达量降至假手术组的84%(与假手术组相比,q=2.230,P=0.029),7 d时降至最低,14～21 d表达量开始上调,21 d时表达量上调至假手术组的66%(与假手术组相比,q=4.681,P＜0.01).(2)缺血再灌注不同时问点髓鞘染色Ias比值不同,再灌注6 h时开始下降(0.91±0.05),与假手术组(1.03 ±0.09)相比,q=3.829,P＜0.01;12 h时有空洞形成,再灌注14 d髓鞘损伤达到高峰,Ias比值降到最低(0.31±0.07),髓鞘脱失明显;21 d的髓鞘Ias比值(0.30±0.06)与14 d(0.31±0.07)相比较差异无统计学意义(q=0.257,P=0.798).轴突变化规律与髓鞘基本相同.结论 Olig1、Nogo-A在脑缺血再灌注损伤过程中呈现动态变化规律,并与白质损伤的变化规律基本相同,提示Olig1、Nogo-A可能参与了再灌注损伤的病理生理过程,并与缺血再灌注白质损伤及修复密切相关.     

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。     

Rosmarinic acid ameliorates hypoxia/ischemia induced cognitive deficits and promotes remyelination

Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.     

Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain

Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris water-maze task, immunohistochemistry for bromodeoxyuridine, as well as serial neuronal and glial markers were analyzed until 28 days after hypoperfusion. There was a significant increase in the number of oligodendrocyte progenitor cells in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. The oligodendrocyte progenitor cells subsequently underwent cell death and the number of oligodendrocytes decreased. In the rat model, treatment with a phosphodiesterase III inhibitor prevented cell death, markedly increased the mature oligodendrocytes, and promoted restoration of white matter and recovery of cognitive decline. These effects were cancelled by using protein kinase A/C inhibitor in the phosphodiesterase III inhibitor group. The results of our study indicate that the mammalian brain white matter tissue has the capacity to regenerate after ischemic injury.     

Dirty-appearing white matter in multiple sclerosis: preliminary observations of myelin phospholipid and axonal loss

"Dirty-appearing white matter" (DAWM) in multiple sclerosis (MS) is defined as a region(s) with ill-defined borders of intermediate signal intensity between that of normal-appearing white matter (NAWM) and that of plaque on T(2)-weighted and proton density imaging. To delineate the histopathology of DAWM, four formalin-fixed cerebral hemisphere slices of three MS patients with DAWM were scanned with T(2)- weighted and proton density sequences. The myelin water fraction (MWF) was obtained by expressing the short T(2) component as a fraction of the total T(2) distribution. Hemispheric sections were then stained with Luxol fast blue (LFB) for myelin phospholipids, for myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) for myelin; Bielschowsky silver impregnation for axons; and for glial fibrillary acidic protein (GFAP) for astrocytes. Compared to NAWM, DAWM showed reduction in MWF, corresponding to a reduction of LFB staining. DAWM also showed reduced Bielschowsky staining. Quantitatively, the change in MWF in DAWM most consistently correlated with the change in LFB staining. The findings of this preliminary study suggest that DAWM is characterized by loss of myelin phospholipids, detected by the short T(2) component, and axonal reduction.     

Human umbilical cord blood cells directly suppress ischemic oligodendrocyte cell death

Previous reports have shown that human umbilical cord blood cells (HUCBCs) administered intravenously 48 hr following middle cerebral artery occlusion reduce infarct area and behavioral deficits of rodents. This cellular therapy is potently neuroprotective and antiinflammatory. This study investigates the effect of HUCBC treatment on white matter injury and oligodendrocyte survival in a rat model of ischemia. Intravenous infusion of 10(6) HUCBCs 48 hr poststroke reduced the amount of white matter damage in vivo as seen by quantification of myelin basic protein staining in tissue sections. To determine whether HUCBC treatment was protective via direct effects on oligodendrocytes, cultured oligodendrocytes were studied in an in vitro model of oxygen glucose deprivation. Active caspase 3 immunohistochemistry and the lactate dehydrogenase assay for cytotoxicity were used to determine that HUCBCs provide protection to oligodendrocytes in vitro. Based on these results, it is likely that HUCBC administration directly protects oligodendrocytes and white matter. This effect is likely to contribute to the increased behavioral recovery observed with HUCBC therapy.     

Prominent white matter lesions develop in Mongolian gerbils treated with 100% normobaric oxygen after global brain ischemia

Summary Carotid arteries were occluded bilaterally for 15 min in two groups of Mongolian gerbils. The first group received 100% oxygen during the first 3 h of reperfusion. During that period, room air was given to the second group. After 3 h, both groups received room air. Brains of gerbils that died within 14 days after occlusion were removed, fixed in formalin and embedded in paraffin. Gerbils that survived 15–28 days were perfused with formalin before their brains were removed and embedded in paraffin. Adjacent, serially cut sections were stained with luxol fast blue (LFB)-H&E, cresyl violet, according to the Bodian method, or immunocytochemically with antisera raised against myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). In brain sections of gerbils receiving 3 h of 100% oxygen, there were circumscribed white matter lesions in the corpus striatum, lateral thalamus, mesencephalon and posterior limb of the internal capsule. Myelin sheaths were swollen, fragmented and were less intensely stained by MBP antiserum. MBP and LFB-stained myelin fragments were present extracellularly and in macrophages. Many axons in these areas appeared undamaged. Previously described ischemic changes were found in gray matter and some areas of white matter in both groups. However, neurons in the deeper laminae of the cerebral cortex appeared to be better preserved in gerbils given oxygen. The results suggest that hyperoxia, if present immediately after transient brain ischemia, may damage myelin more severely than other cellular elements.     

Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat

Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post‐injury time points, as compared with sham‐injured controls (P ≤ 0.05). Accumulation of β‐amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post‐injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase‐3 co‐labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post‐injury (P ≤ 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI.