Traumatic brain injury (TBI) triggers neuronal death mechanisms that significantly induce neuronal loss and neurological dysfunction. Our previous study revealed that Sirt1 could improve the neuroprotective effect by reducing the astrocyte activation after TBI. Nevertheless, the underlying mechanisms of Sirt1 attenuating astrocyte activation still remain unclear. The following study examined whether the protection of Sirt1 in nigrostriatal pathway injury is associated with autophagy regulation. We established a nigrostriatal pathway injury in the mouse brain in order to mimic the traumatic brain injury and up-regulated Sirt1 expression by resveratrol. Consequently, we analyzed the effect of Sirt1 up-regulation on LC3 and monitored the LC3 localization in the astrocytes, microglial cells and neurons. We found that the Sirt1 up-regulation by resveratrol increased the expression of LC3 around the lesion site after injury. Confocal results showed that Sirt1 up-regulation increased the expression of LC3 in astrocytes and decreased the expression in the neurons, while low effect was found on the microglial cells. Moreover, compared the resveratrol treatment groups, a typical nucleocytoplasmic localization with strong distribution in the nucleus (in astrocyte and neurons) was observed in the control group (treated with DMSO). To sum up, our data suggested that regulation of Sirt1 expression could enhance autophagy in the astrocytes and decrease the expression in the neurons. This mechanism, which may probably relate to the distribution of LC3 in cytoplasm and nucleus, provides a new theoretical basis for exploring the neuroprotective mechanism of Sirt1 after brain injury.

Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. The present study aimed to assess whether the inhibition of aquaporin 4 had an analgesic effect on neuropathic pain and whether the inhibition of astrocytic activation and ERK pathway was involved in the analgesic effect of TGN-020. We thus found that TGN-020 upregulated the threshold of thermal and mechanical allodynia, downregulated the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α, attenuated the astrocytic activation and suppressed the activation of mitogen-activated protein kinase pathways in the spinal dorsal horn and dorsal root ganglion. Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury–induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion.

Matrix metalloproteinases (MMPs) cleave almost all components of the extracellular matrix (ECM) and cause acute neurovascular disruption and parenchymal destruction. Previously, MMPs inhibition was considered to be a therapeutic strategy in early stages of ischemia. This study was designed to investigate whether early MMPs inhibition could promote the recovery of cerebral ischemia. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 1 h and reperfusion. The rats were divided into three groups: sham + vehicle (S + V) group, MCAO + vehicle (M + V) group, and MCAO + GM6001 (M + G) group. Infarct volume was assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the expression of GFAP, IBA1, p-ERK, ERK, and MMP9 were evaluated by Western blot and immunofluorescence staining on 1, 4, 7, and 14 days after MCAO. Neuronal apoptosis was assessed by Fluoro-Jade C staining. The results showed that MMPs inhibition significantly increased the infarct volume and the expressions of GFAP and IBA1 in the M + V group were much higher than those in the M + G group; whereas the expression of p-ERK was upregulated in both the M + V and M + G groups. These findings suggest that MMPs promote the activation and migration of astrocytes and microglia to form protected zone in the penumbra and lessen the infarct volume after cerebral ischemic stroke.

Brain injury leads to complex cellular and molecular interactions within the central nervous system. As the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Here we investigated the roles of PDGFRβ signaling in regulating astrocyte reactivity and scar formation in mice following traumatic brain injury (TBI). The expression and distribution of phosphorylated PDGFRβ was analyzed, and its cell type-specific expression was verified with double labeling of astrocytes (GFAP), microglia (IBA1), oligodendrocyte precursor cells (OPC) (NG2) and leukocytes (CD45). We found PDGFRβ was activated around the injury site after TBI, and primarily expressed in astrocytes, microglia, OPC and leukocytes in the boundary of the lesion site, suggesting PDGFRβ was involved in glial scar formation. Then the PDGFR inhibitor (AG1296) was administered following TBI. Reactive astrocytes were significantly inhibited in AG1296-treated mice. Furthermore, AG1296-treatment attenuated reactive leukocytes, OPC and astrocytes and pronouncedly disrupted of glial scar formation after TBI. These findings prove that PDGFRβ signaling inhibited reactive glia-mediated scar formation after TBI in mice.

BACKGROUND:Astrocyte activation is a hallmark of traumatic brain injury resulting in neurological dysfunction or death for an overproduction of inflammatory cytokines and glial scar formation. Both the silent mating type information (Sirt1) expression and mitogen-activated protein kinase (MAPK) signal pathway activation represent a promising therapeutic target for several models of neurodegenerative diseases. We investigated the potential effects of Sirt1 upregulation and MAPK pathway pharmacological inhibition on astrocyte activation in vitro and in vivo. Moreover, we attempted to confirm the underlying interactions between Sirt1 and MAPK pathways in astrocyte activation after brain injury.METHODS:The present study employs an interleukin-1β (IL-1β) stimulated primary cortical astrocyte model in vitro and a nigrostriatal pathway injury model in vivo to mimic the astrocyte activation induced by traumatic brain injury. The activation of GFAP, Sirt1, and MAPK pathways were detected by Western blot; astrocyte morphological hypertrophy was assessed using immunofluorescence staining; in order to explore the neuroprotective effect of regulation Sirt1 expression and MAPK pathway activation, the motor and neurological function tests were assessed after injury.RESULTS:GFAP level and morphological hypertrophy of astrocytes are elevated after injury in vitro or in vivo. Furthermore, the expressions of phosphorylated extracellular regulated protein kinases (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated p38 activation (p-p38) are upregulated, but the Sirt1 expression is downregulated. Overexpression of Sirt1 significantly increases the p-ERK expression and reduces the p-JNK and p-p38 expressions. Inhibition of ERK, JNK, or p38 activation respectively with their inhibitors significantly elevated the Sirt1 expression and attenuated the astrocyte activation. Both the overproduction of Sirt1 and inhibition of ERK, JNK, or p38 activation can alleviate the astrocyte activation, thereby improving the neurobehavioral function according to the modified neurological severity scores (mNSS) and balance latency test.CONCLUSIONS:Thus, Sirt1 plays a protective role against astrocyte activation, which may be associated with the regulation of the MAPK pathway activation induced by brain injury in vitro and in vivo.

Methylmercury (MeHg), an extremely dangerous environmental pollutant, accumulating preferentially in central nervous system, causes a series of cytotoxic effects. The present study explored the mechanisms which contribute to MeHg-induced neurotoxicity focusing on the oxidative stress in rat cerebral cortex. In addition, the protective effects of alpha-lipoic acid (LA), a potent antioxidant on MeHg-mediated neuronal injury, was also investigated in current study. A MeHg poisoning model was established as 64 rats randomly divided into 4 groups of which saline control group, MeHg-treated groups (4 and 12 molkg(-1)), and LA pretreatment (35 molkg(-1)) group, respectively. After administration of 12 molkg(-1) MeHg for 4 weeks, it was found that obvious pathological changes and apoptosis in neuronal cells. Meanwhile, total Hg levels elevated significantly, superoxide dismutase (SOD) and gluthathione peroxidase (GSH-Px) activities were inhibited, and ROS formation elevated, which might be critical to aggravate oxidative stress in cerebral cortex. In addition, NF-E2-related factor 2 (Nrf2) pathways were activated, as heme oxygenase-1 (HO-1) and -glutamylcysteine synthetase heavy subunit (-GCSh) expressions were up-regulated obviously by MeHg exposure. Moreover, activities of Na+-K+-ATPase and Ca2+-ATPase were inhibited, leading to intracellular calcium (Ca2+) overload. LA pre-treatment partially reduced MeHg neurotoxic effects via anti-oxidation pathways. In conclusion, these findings clearly indicated that MeHg aggravated oxidative stress and Ca2+ overload in cerebral cortex. LA possesses the ability to prevent MeHg neurotoxicity through its anti-oxidative properties. (C) 2016 Wiley Periodicals, Inc.

Nigrostriatal pathway injury is one of the traumatic brain injury models that usually lead to neurological dysfunction or neuron necrosis. Resveratrol-induced benefits have recently been demonstrated in several models of neuronal degeneration diseases. However, the protective properties of resveratrol against neurodegeneration have not been explored definitely. Thus, we employ the nigrostriatal pathway injury model to mimic the insults on the brain. Resveratrol decreased the p-ERK expression and increased the p-JNK expression compared to the DMSO group, but not alter the p38 MAPK proteins around the lesion site by Western blot. Prior to the injury, mice were infused with resveratrol intracerebroventricularly with or without JNK-IN-8, a specific c-JNK pathway inhibitor for JNK1, JNK2 and JNK4. The study assessed modified improved neurological function score (mNSS) and beam/walking test, the level of inflammatory cytokines IL-1β, IL-6 and TNF-α, and striatal expression of Bax and Bcl-2 proteins associated with neuronal apoptosis. The results revealed that resveratrol exerted a neuroprotective effect as shown by the improved mNSS and beam latency, anti-inflammatory effects as indicated by the decreased level of IL-1β, TNF-α and IL-6. Furthermore, resveratrol up-regulated the protein expression of p-JNK and Bcl-2, down-regulated the expression of Bax and the number of Fluoro-Jade C (FJC) positive neurons. However, these advantages of resveratrol were abolished by JNK-IN-8 treatment. Overall, we demonstrated that resveratrol treatment attenuates the nigrostriatal pathway injury-induced neuronal apoptosis and inflammation via activation of c-JNK signaling.

目的 探讨莱菔硫烷(sulforaphane,SFN)对莱菔硫烷(sulforaphane,SFN)所致大鼠急性肾损伤的保护作用.方法 清洁级Wistar大鼠30只按体重随机分5组,每组6只,分别为对照组,低、中、高剂量染汞组,SFN干预组.对照组及各染汞组皮下注射生理盐水,SFN干预组皮下注射2 mg/kg SFN;2h后,对照组腹腔注射生理盐水,其他四组腹腔注射2.2、4.4、8.8、8.8μmol/kg HgCl2,连续3d,染毒容量均为5ml/kg.于最后一次染毒结束后,测定尿液中Hg及尿蛋白含量,碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)和β-N-乙酰氨基葡萄糖苷酶(NAG)活力;腹主动脉采血测定血清尿素氮(BUN)含量;测定肾皮质中Hg含量和谷胱甘肽(GSH)、丙二醛(MDA)水平及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力.分析各组各项指标差异.结果 与对照组比较,各剂量染汞组大鼠尿Hg、肾皮质Hg含量,尿蛋白和血清BUN含量,尿NAG、LDH和ALP活力,肾皮质中GSH和MDA含量显著升高(P＜0.05或P＜0.01);肾皮质SOD和GSH-Px活力显著降低(P＜0.05或P＜0.01).与8.8μmol/kg HgCl2组比较,SFN干预组尿蛋白和血清BUN含量、尿NAG、LDH和ALP活力、肾皮质GSH、MDA含量均显著下降(P＜0.05或P＜0.01);肾皮质SOD和GSH-Px活力显著升高(P＜0.01),而尿汞、肾皮质汞含量间差异无统计学意义(P＞0.05).结论 莱菔硫烷对汞所致大鼠急性肾毒性有一定的保护作用.

目的 探讨姜黄素对汞致大鼠肾损伤的影响,为汞中毒的发病机制和防治提供实验依据.方法 将30只清洁级Wistar大鼠按体重随机分为5组,分别为对照(生理盐水)组和2.2、4.4、8.8 μmol/kg氯化汞染毒组及姜黄素干预(8.8mol/kg氯化汞+100 mg/kg姜黄素)组,每组6只,雌雄各半.采用腹腔注射方式染毒氯化汞,染毒容量为5ml/kg;采用皮下注射方式染毒姜黄素,染毒容量为1 ml/kg,每天1次,连续染毒3d.测定肾皮质汞含量、肾皮质细胞ROS水平和细胞凋亡率及肾皮质Nrf2、HO-1、γ-GCS和Gpx-1 mRNA和蛋白的表达水平.结果 与对照组比较,各剂量氯化汞染毒组和姜黄素干预组大鼠肾皮质汞含量和细胞凋亡率均升高,4.4、8.8 μmol/kg氯化汞染毒组和姜黄素干预组大鼠肾皮质细胞ROS水平均升高,差异有统计学意义(P＜0.05,P＜0.01).与对照组比较,各剂量氯化汞染毒组和姜黄素干预组大鼠肾皮质Mrf2、HO-1、γ-GCS mRNA的表达水平均升高,而GPx-1 mRNA的表达水平均降低,除2.2 μmol/kg氯化汞染毒组HO-1、GPx-1mRNA的表达水平及姜黄素干预组GPx-1mRNA的表达水平外,差异均有统计学意义(P＜0.05,P＜0.01).与对照组比较,各剂量氯化汞染毒组和姜黄素干预组大鼠肾皮质Nrf2、HO-1、γ-GCS蛋白的表达水平均升高,而Gpx-1蛋白的表达水平均降低,除2.2 μmol/kg氯化汞染毒组γ-GCS蛋白的表达水平外,差异均有统计学意义(P＜0.05,P＜0.01).且随着氯化汞染毒剂量的升高,大鼠肾皮质汞含量、ROS水平和细胞凋亡率及肾皮质Nrf2、HO-1、γ-GCS蛋白和mRNA的表达水平均呈上升趋势,而GPx-1蛋白的表达水平呈下降趋势.与8.8 μmol/kg氯化汞染毒组比较,姜黄素干预组大鼠肾皮质ROS水平和细胞凋亡率均下降,差异有统计学意义(P＜0.01),而肾皮质汞含量无明显改变;肾皮质Nrf2、HO-1、γ-GCS和GPx-1mRNA的表达水平均升高,差异有统计学意义(P＜0.01);肾皮质γ-GCS、HO-1蛋白的表达水平均升高,而Nrf2、GPx-1蛋白的表达水平降低,差异有统计学意义(P＜0.01).结论 姜黄素可通过激活Nrf2信号通路对汞致大鼠肾损伤产生一定的拮抗作用.

This study was undertaken to examine the function of extracellular signal-regulated kinase (ERK) signaling pathway on the proliferation and activation of microglia/macrophage and astrocytes after brain injury in mice. The result of Western blot showed that p-ERK was immediately activated after injury (<4h), but the duration was short (<4 days). According to immunofluorescence double staining, it was found that at 4 and 8h after injury, p-ERK was expressed in microglia/macrophages, and that more cells were co-expressed by p-ERK and IBA-1 (microglia/macrophage marker) at 8h; at days 1 and 4, p-ERK was expressed in astrocytes, and more cells were co-expressed by p-ERK and GFAP (astrocyte marker) at day 4. After injury, the mice were injected with U0126 (MAPK/ERK signaling pathway inhibitor) via the femoral vein. Compared with those injected with DMSO, the cell number co-expressed by p-ERK and IBA-1 or GFAP significantly decreased (P<0.05). The increase of microglia/macrophage and astrocyte caused by injury was remitted, and the positive cell number significantly decreased (P<0.05). Western blot showed that the expression quantity of IBA-1 and GFAP significantly decreased (P<0.05). Furthermore, the ERK signaling pathway was involved in the proliferation and activation of the two glial cells types and improved long-term neurobehavioral function after brain injury. Therefore, the exploration of the formation mechanism of glial scar after injury and further research on the therapeutic method of neural regeneration are essential.

目的 探讨莱菔硫烷(sulforaphane,SFN)对汞所致肝脏氧化应激的拮抗作用. 方法 实验用Wistar大鼠60只,按体重随机分成6组:对照组,DMSO对照组,低、中、高剂量染汞组、SFN预处理组.对照组和染汞组皮下注射生理盐水,DMSO对照组皮下注射DMSO,SFN预处理组皮下注射2 mg/kg SFN;2 h后,对照组及DMSO对照组腹腔注射生理盐水,低、中、高剂量染汞组分别腹腔注射0.6、1.2、2.4 mg/kg HgCl2,SFN预处理组腹腔注射2.4 mg/kg HgCl2.注射容量为5ml/kg.连续预处理与染毒3d.于最后一次染汞24 h后,每组取6只大鼠,麻醉后处死,冰浴下切取肝组织,测定肝Hg含量、还原型谷胱甘肽(GSH)含量、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GPx)活力及丙二醛(MDA)含量.每组其余4只大鼠,制备肝脏单细胞悬液,测定肝细胞活性氧簇(ROS)及早期细胞凋亡率. 结果 与对照组比较,随染汞各组染Hg剂量的升高,肝组织Hg、GSH、MDA含量、肝细胞ROS水平及早期细胞凋亡率逐渐升高,SOD及GPx活力逐渐降低,呈现剂量-效应关系(P＜0.01).2.4 mg/kg HgC12组肝组织Hg、GSH、MDA含量、肝细胞ROS水平及早期细胞凋亡率显著升高,SOD及GPx活力显著降低,差异有统计学意义(P＜0.05或P＜0.01).SFN预处理组肝组织Hg含量与2.4 mg/kg HgCl2组相比未见明显差异(P＞0.05),GSH、MDA含量、ROS水平及早期细胞凋亡率显著下降,SOD及GPx活力显著升高,差异有统计学意义(P＜0.05或P＜0.01). 结论 SFN对汞所致肝脏氧化应激具有一定程度的拮抗作用.

目的 探讨莱菔硫烷(sulforaphane,SFN)通过诱导核转录因子NF-E2相关因子2(nuclear factor erthroid 2-related factor2,Nrf2)通路激活对汞所致肝脏氧化损伤的拮抗作用及其机制.方法 将60只健康成年SPF级Wistar大鼠按体重随机分成6组,分别为对照(生理盐水)组,DMSO对照组,0.6、1.2、2.4 mg/kg氯化汞染毒组及SFN预处理(2.4 mg/kg氯化汞+2 mg/kg SFN)组,每组10只,雌雄各半.采用皮下注射SFN溶液,其余各组皮下注射生理盐水,DMSO对照组皮下注射DMSO;2 h后,腹腔注射氯化汞溶液,染毒容量均为5 ml/kg,每日1次,连续染毒3d.测定血清乳酸脱氢酶(lactate dehydrogenase,LDH)及丙氨酸氨基转移酶(alanine transaminase,ALT)活力和肝细胞ROS水平以及肝组织Nrf2、血红素单加氧酶-1(HO-1)、γ-谷氨酰半胱氨酸合成酶催化亚基(γ-GCSh)的mRNA及蛋白的表达水平.结果 与对照组比较,各剂量氯化汞染毒组大鼠血清LDH、ALT活力(除0.6 mg/kg氯化汞染毒组ALT活力外)和肝细胞ROS水平以及1.2 mg/kg氯化汞染毒组大鼠肝组织HO-1 mRNA的表达水平和2.4 mg/kg氯化汞染毒组大鼠肝组织Nrf2、HO-1、γ-GCSh mRNA的表达水平及1.2、2.4 mg/kg氯化汞染毒组大鼠肝组织Nrf2、HO-1、γ-GCSh蛋白的表达水平均升高,差异均有统计学意义(P＜0.05,P＜0.01);且随着氯化汞染毒剂量的升高,大鼠血清LDH、ALT活力和肝细胞ROS水平及肝组织Nrt2、HO-1、γ-GCSh蛋白和mRNA的表达水平均呈逐渐上升的趋势.与2.4 mg/kg氯化汞染毒组比较,SFN预处理组大鼠血清LDH、ALT的活力和肝细胞ROS水平均较低,而肝组织Nrf2、HO-1、γ-GCSh蛋白和mRNA的表达水平均较高,差异均有统计学意义(P＜0.05,P＜0.01).结论 SFN可通过诱导Nrf2-ARE通路激活,促使肝细胞Nrf2及其下游抗氧化酶HO-1、γ-GCSh表达,进而清除细胞内过量的ROS,从而拮抗汞所致肝脏氧化应激损伤.

将Wistar大鼠分5组,分别为对照组、低汞组、中汞组、高汞组、莱菔硫烷(SFN)干预组,连续处理3d,测定肾皮质中汞含量、肾细胞ROS水平和凋亡率,测定肾皮质Nrf2、HO-1、γ-GCS、Gpx-1的mRNA和蛋白表达水平.结果显示,SFN可降低ROS及凋亡率水平,并可使肾皮质mRNA和蛋白表达均升高.提示莱菔硫烷可拮抗汞所致大鼠肾脏氧化损伤.

Traumatic brain injury triggers a series of damaged processes, such as neuronal death and apoptosis, inflammation and scar formation, which contribute to evolution of brain injury. The present study investigated the neuroprotective effects of batroxobin, a drug widely used clinically for ischemia, in a nigrostriatal pathway injury model. Mice subjected to the nigrostriatal pathway injury were injected with batroxobin (30 BU/kg) or vehicle immediately after injury. The behavioral studies showed that batroxobin could improve the motor function in injured mice in long term. Batroxobin also reduced neuronal apoptosis and inflammation at the acute stage. Moreover, administration of batroxobin attenuated the scar formation and reduced the lesion size at 4 and 14days after brain injury. These results suggest that batroxobin has beneficial effects on the nigrostriatal pathway injury, indicating a potential clinical application.

This study discussed the protection mechanism of Pre-HBO to the complete spinal cord transaction (CSCT) rats in early time after impairs. Male Wistar rats were preconditioned with consecutive 5 cycles of 1-h HBO exposures (2.5 atmospheres absolute [ATA], 100% O2) at a 24-h interval. At 24 h after the last HBO pretreatment, rats underwent complete spinal cord transaction at T10-11. Spinal cord transaction produced marked neuronal death and neurological dysfunction in animals. Pre-HBO enhanced neurobehavioral scores(BBB locomotor scale), as well as the activities of superoxide dismutase (SOD) which obviously in blood samples at 8h after CSCT(p<0.01), but obviously in tissue samples at 24h after CSCT(p<0.01). Neuronal apoptosis could be found at 8h, but most of them were found at 24h and only a few was found at 3d. Pre-HBO obviously reduced neuronal apoptosis in dorsal horn at 24h after CSCT(p<0.05). We conclude that Pre-HBO reduced spinal cord transaction injury by increasing activities of SOD and suppressing mitochondrial apoptosis pathway which finally increase the hindlimb locomotor function.

Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration.

Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.

目的 探讨硫酸皮肤素(DS)在小鼠脑外伤后的经时表达及其与纤维性瘢痕产生的相关性. 方法 选用10周龄小鼠制备黑质纹状体通路损伤模型,术后1、4、7、14d取脑行冷冻切片.应用GD3A12和LKN1抗体特异性识别硫酸软骨素的一个亚型——DS的表达,同时应用纤连蛋白(FN)抗体探讨纤维性瘢痕的产生过程,应用免疫荧光法探讨两者的相关性. 结果 在正常成年小鼠大脑中,GD3A12和LKN1免疫反应只出现在脑膜及脑表面的血管.在伤后4d的鼠脑,损伤周边的某些细胞中发现DS的表达,其后在损伤部位的纤维性瘢痕中DS表达增加.双重免疫荧光显示,DS与FN共同定位于脑膜细胞迁移而形成的纤维性瘢痕.虽然纤维性瘢痕也有巨噬细胞和反应性星形胶质细胞紧密包绕,但DS未表达在巨噬细胞和星形胶质细胞. 结论 在脑损伤后,DS的定位只限于纤维性瘢痕的纤连蛋白阳性细胞,由此推论DS可能在纤维性瘢痕形成中起着一定的作用.