M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury

After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.

Poly(ADP-ribose)polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway

Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.

Microglia:a promising therapeutic target in spinal cord injury

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

TMEM16F may be a new therapeutic target for Alzheimer's disease

TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F level has been also found to participate in microglial phagocytosis and transformation.Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease.However,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease.In this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD.We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome.Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice.After TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was alleviated.We used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s disease.The levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control group.TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand interleukin-18.This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin.Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome.These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.

Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Rutin pretreatment promotes microglial M1 to M2 phenotype polarization

Microglial cells are important resident innate immune components in the central nervous system that are often activated during neuroinflammation.Activated microglia can display one of two phenotypes,M1 or M2,which each play distinct roles in neuroinflammation.Rutin,a dietary flavonoid,exhibits protective effects against neuroinflammation.However,whether rutin is able to influence the M1/M2 polarization of microglia remains unclear.In this study,in vitro BV-2 cell models of neuroinflammation were established using 100 ng/mL lipopolysaccharide to investigate the effects of 1-hour rutin pretreatment on microglial polarization.The results revealed that rutin pretreatment reduced the expression of the proinflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6 and increased the secretion of interleukin-10.Rutin pretreatment also downregulated the expression of the M1 microglial markers CD86 and inducible nitric oxide synthase and upregulated the expression of the M2 microglial markers arginase 1 and CD206.Rutin pretreatment inhibited the expression of Toll-like receptor 4 and myeloid differentiation factor 88 and blocked the phosphorylation of I kappa B kinase and nuclear factor-kappa B.These results showed that rutin pretreatment may promote the phenotypic switch of microglia M1 to M2 by inhibiting the Toll-like receptor 4/nuclear factor-kappa B signaling pathway to alleviate lipopolysaccharide-induced neuroinflammation.

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune modulation.One of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment.In the present study,immortalized microglial cells were pretreated with L.barbarum extract for 1 hour and then treated with oligomeric Aβfor 23 hours.The results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of M1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of M2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial cells.The results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions,and promote M2 polarization.

Interleukin-4 affects microglial autophagic flux

Interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic cytokines.Recently,increasing evidence has suggested that autophagy regulates innate immunity by affecting M1/M2 polarization of microglia/macrophages.However,the role of interleukin-4 in microglial autophagy is unknown.In view of this,BV2 microglia were treated with 0,10,20 or 50 ng/mL interleukin-4 for 24,48,or 72 hours.Subsequently,light chain 3-II and p62 protein expression levels were detected by western blot assay.BV2 microglia were incubated with interleukin-4(20 ng/mL,experimental group),3-methyladenine(500μM,autophagy inhibitor,negative control group),rapamycin(100 nM,autophagy inductor,positive control group),3-methyladenine+interleukin-4(rescue group),or without treatment for 24 hours,and then exposed to amyloid-β(1μM,model group)or vehicle control(control)for 24 hours.LC3-II and p62 protein expression levels were again detected by western blot assay.In addition,expression levels of multiple markers of M1 and M2 phenotype were assessed by real-time fluorescence quantitative polymerase chain reaction,while intracellular and supernatant amyloid-βprotein levels were measured by enzyme-linked immunosorbent assay.Our results showed that interleukin-4 induced microglial autophagic flux,most significantly at 20 ng/mL for 48 hours.Interleukin-4 pretreated microglia inhibited blockade of amyloid-β-induced autophagic flux,and promoted amyloid-βuptake and degradation partly through autophagic flux,but inhibited switching of amyloid-β-induced M1 phenotype independent on autophagic flux.These results indicate that interleukin-4 pretreated microglia increases uptake and degradation of amyloid-βin a process partly mediated by autophagy,which may play a protective role against Alzheimer’s disease.

Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes

Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

Selective modulation of M2 microglia phenotype for stroke treatment

Aim Following cerebral isehemia, microglia respond to the injury acting as the first defense of central nervous system. Activated microglia play a dual role in the ischemie injury depending on the phenotype of micro- gila, including deleterious M1 phenotype and neuroprotective M2 phenotype. However, microglia show transient M2 phenotype followed by a transition to M1 phenotype aggravating the ischemic injury. Many signal pathways par- ticipate in the modulation of microglial polarization , presenting potential therapeutic targets for selectively inducing the polarization of M2 microglia. In this review, we discuss M2 microglia phenotype mediated neuroprotective role and the signaling cascades controlling microglial phenotype after ischemic stroke.

Necroptosis plays a crucial role in the exacerbation of retinal injury after blunt ocular trauma

Retinal injury after blunt ocular trauma may directly affect prognosis and lead to vision loss.To investigate the pathological changes and molecular mechanisms involved in retinal injury after blunt ocular trauma,we established a weight drop injury model of blunt ocular trauma in male Beagle dogs.Hematoxylin-eosin staining,immunofluorescence staining,western blotting,and TUNEL assays were performed to investigate retinal injury within 14 days after blunt ocular trauma.Compared with the control group,the thicknesses of the inner and outer nuclear layers,as well as the number of retinal ganglion cells,gradually decreased within 14 days after injury.The number of bipolar cells in the inner nuclear layer began to decrease 1 day after injury,while the numbers of cholinergic and amacrine cells in the inner nuclear layer did not decrease until 7 days after injury.Moreover,retinal cell necroptosis increased with time after injury;it progressed from the ganglion cell layer to the outer nuclear layer.Visual electrophysiological findings indicated that visual impairment began on the first day after injury and worsened over time.Additionally,blunt ocular trauma induced nerve regeneration and Müller glial hyperplasia;it also resulted in the recruitment of microglia to the retina and polarization of those microglia to the M1 phenotype.These findings suggest that necroptosis plays an important role in exacerbating retinal injury after blunt ocular trauma via gliosis and neuroinflammation.Such a role has important implications for the development of therapeutic strategies.

腺苷预处理对脑缺血再灌注大鼠小胶质细胞极化及神经损伤的影响

目的探讨大鼠脑缺血再灌注(IR)损伤后小胶质细胞表型的变化以及腺苷对脑IR损伤大鼠的神经损伤的作用。方法将36只健康雄性Sprague Dawley大鼠按随机数字表法分为假手术(Sham)组、IR组和腺苷预处理(AP)组,每组12只。AP组大鼠造模前每天腹腔注射2 mL腺苷注射液,连续3 d;Sham组及IR组大鼠每天腹腔注射2 mL生理盐水,连续3 d。IR组和AP组大鼠采用线栓法构建大脑中动脉栓塞模型;Sham组大鼠仅分离颈动脉,不结扎血管。造模2 h后,采用5分制神经行为学评分对各组大鼠进行神经行为学评估。恢复大脑中动脉血流灌注24 h后处死各组大鼠,取出脑组织,采用苏木精-伊红(HE)染色观察缺血半暗带区域脑组织形态学改变,免疫荧光染色法检测M1型小胶质细胞标志物和M2型小胶质细胞标志物的共表达情况,采用实时荧光定量聚合酶链式反应法(qRT-PCR)检测2组大鼠脑组织中M1型小胶质细胞释放的促炎因子诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和M2型小胶质细胞释放的抗炎因子IL-4、IL-10、转化生长因子-β(TGF-β)的相对表达量。结果IR组及AP组大鼠神经行为学评分显著高于Sham组,IR组大鼠神经行为学评分显著高于AP组(P<0.05)。HE染色结果显示,Sham组大鼠脑组织中细胞结构完整,细胞核清晰可见,细胞排列紧密,无间质水肿;IR组大鼠脑组织中细胞结构明显破坏,细胞排列不整齐,间质疏松,胞体内出现空泡;AP组大鼠脑组织中细胞结构较IR组完整,正常细胞数量较多,排列较整齐,细胞核较完整。免疫荧光染色结果显示,IR组、AP组大鼠脑缺血半暗带区域M1型、M2型小胶质细胞数量显著高于Sham组,IR组大鼠M1型小胶质细胞数量显著高于AP组,M2型小胶质细胞数显著低于AP组(P<0.05)。qRT-PCR结果显示,IR组、AP组大鼠脑组织中促炎细胞因子TNF-α、IL-1β、iNOS和抗炎细胞因子IL-4、IL-10、TGF-β相对表达量显著高于Sham组(P<0.05);AP组大鼠中促炎细胞因子TNF-α、IL-1β、iNOS相对表达量显著低于IR组(P<0.05),抗炎细胞因子IL-4、IL-10、TGF-β相对表达量显著高于IR组(P<0.05)。结论AP可促进大鼠脑IR损伤后小胶质细胞由M1型极化为M2型,抑制促炎因子的释放,增加抗炎因子的释放,对脑IR损伤大鼠具有神经保护作用。

ROS-responsive 18β-glycyrrhetic acid-conjugated polymeric nanoparticles mediate neuroprotection in ischemic stroke through HMGB1 inhibition and microglia polarization regulation

Ischemic stroke is an acute and serious cerebral vascular disease,which greatly affects people’s health and brings huge economic burden to society.Microglia,as important innate immune components in central nervous system(CNS),are double-edged swords in the battle of nerve injury,considering their polarization between pro-inflammatory M1 or anti-inflammatory M2 phenotypes.High mobility group box 1(HMGB1)is one of the potent pro-inflammatory mediators that promotes the M1 polarization of microglia.18β-glycyrrhetinic acid(GA)is an effective intracellular inhibitor of HMGB1,but of poor water solubility and dose-dependent toxicity.To overcome the shortcomings of GA delivery and to improve the efficacy of cerebral ischemia therapy,herein,we designed reactive oxygen species(ROS)responsive polymer-drug conjugate nanoparticles(DGA)to manipulate microglia polarization by suppressing the translocation of nuclear HMGB1.DGA presented excellent therapeutic efficacy in stroke mice,as evidenced by the reduction of infarct volume,recovery of motor function,suppressed of M1 microglia activation and enhanced M2 activation,and induction of neurogenesis.Altogether,our work demonstrates a close association between HMGB1 and microglia polarization,suggesting potential strategies for coping with inflammatory microglia-related diseases.

桃叶珊瑚苷通过调节小胶质细胞M1/M2极化抑制神经炎症

目的:探究桃叶珊瑚苷(aucubin)对脂多糖(LPS)诱导建立的体外神经炎症模型的影响。方法:用LPS诱导N9细胞激活建立体外神经炎症模型,加入桃叶珊瑚苷处理细胞24 h,对细胞上清一氧化氮(NO)含量和细胞活力进行检测,显微镜拍摄细胞形态,免疫荧光法检测小胶质细胞特异标志物Iba-1水平,Flowsight检测CD11b水平和CD86/CD206比值,并用试剂盒检测IL-4,IL-10,TGF-β,IL-1β,IL-6,TNF-α水平。结果:与模型对照组比较,桃叶珊瑚苷组可有效改善细胞形态,降低细胞上清NO含量,降低细胞标志物CD11b水平和CD86/CD206比值,并调节炎症因子的释放。结论:桃叶珊瑚苷可能是通过调控炎症因子的释放,促进小胶质细胞由M1型向M2型转化,从而抑制N9小胶质细胞的激活,最终抑制LPS诱导的神经炎症。

柴胡皂苷D对脑出血大鼠神经保护作用的机制研究

目的评价柴胡皂苷D对脑出血大鼠神经元损伤的影响,并初步探讨其作用机制。方法SD大鼠通过尾状核注入尾静脉自体血建立大鼠脑出血模型,分为假手术组、模型组、柴胡皂苷D组(8 mg/kg)、Toll样受体4(TLR4)激活剂(RS09)组(25μg/只)、TLR4抑制剂(TAK-242)组(0.5 mg/kg)、柴胡皂苷D+TLR4激活剂组,每组20只。各组干预给药结束后,进行神经功能缺损评分;干-湿重法检测脑含水量;伊文思蓝法检测血-脑屏障通透性;取血肿周围组织,ELISA法检测凝血酶-抗凝血酶(TAT)复合物水平;HE染色及TUNEL染色检测神经元损伤及凋亡率;免疫荧光共定位法检测M1型激活小胶质细胞(标记抗体为CD11b)与小胶质细胞(标记抗体为Iba-1)共表达水平;Western blotting法检测IL-1β、IL-6、IL-10、TLR4、髓样分化因子88(MyD-88)、核转录因子-κB(NF-κB)、蛋白酶激活受体-1(PAR-1)、B类清道夫受体(CD36)表达水平。结果与假手术组相比,模型组EB含量、脑含水量、神经功能缺损评分、TAT复合物水平均明显升高,CD11b+Iba-1+水平、IL-10、CD36表达明显降低,TLR4、MyD-88、p-NF-κB/NF-κB、PAR-1蛋白表达明显升高(均P<0.05)。阻断TLR4活化及给予柴胡皂苷D干预处理,均可同等程度的改善脑出血大鼠病理症状,M1促炎相关因子IL-6、IL-1β表达明显下降,M2型抗炎相关因子IL-10、CD36表达明显升高(均P<0.05)。TLR4激活剂可明显削弱柴胡皂苷D的上述作用(P<0.05)。结论柴胡皂苷D可改善脑出血大鼠脑水肿、神经元炎性损伤凋亡等病理症状,且其改善作用可能与阻断TLR4通路介导的小胶质细胞M1型活化有关。

Deviation matrix and asymptotic variance for GI/M/1-type Markov chains

We investigate deviation matrix for discrete-time GI/M/1-type Markov chains in terms of the matrix-analytic method, and revisit the link between deviation matrix and the asymptotic variance. Parallel results are obtained for continuous-time GI/M/1-type Markov chains based on the technique of uniformization. We conclude with A. B. Clarke＇s tandem queue as an illustrative example, and compute the asymptotic variance for the queue length for this model.

小胶质细胞表型在反复轻度脑创伤模型大鼠中的变化研究

目的探讨大鼠反复轻度脑创伤（rmTBI）N小胶质细胞表型的变化。方法雄性SD大鼠60只，按随机数字表法分为假手术组、伤后1周、2周、4周和6周组，每组12只。后4组大鼠采用控制性皮质撞击（CCn法制备大鼠rmTB[模型，假手术组仅开骨窗，不做打击。分别于伤后不同时间每组取6只大鼠，免疫荧光染色检测受损脑皮层Iba—1阳性小胶质细胞，流式细胞技术检测受损脑组织中小胶质细胞表型的变化。结果与假手术组比较，伤后1周、6周组大鼠受损脑组织皮层Iba-1阳性小胶质细胞比例显著增3n（分别为19％、12％），差异有统计学意义（P〈0．05）。流式细胞仪检测显示CD45LOW/CD11B＋矿细胞即小胶质细胞，约占CD11b＋细胞的90％；与假手术组比较，rmTBI伤后1、2、4和6周M1型小胶质细胞增加，差异有统计学意义（P〈0．05），其中伤后6周M1型小胶质细胞增加最为明显；与假手术组比较，rmTBI伤后1、2、4周M2型小胶质细胞均增加，差异有统计学意义（P〈0．05），其中伤后2周M2型小胶质细胞增加最为显著，6周时基本趋于基线水平。结论大鼠rmTBI后存在一定程度的小胶质细胞表型的变化，其不同表型的差异表达可能在大鼠rmTBI的病理生理过程中发挥重要作用。