细胞黏附分子(ICAM-1)在大鼠弥漫性脑损伤中的表达意义

目的探讨ICAM—1在大鼠弥漫性脑损伤中的表达及意义。方法采用Marmarou方法获得大鼠弥漫性脑损伤模型．实时定量RT—PCR、S—P免疫组化法分别测定ICAM—1蛋白和mRNA在外伤后不同时间点的表达变化．干湿重法测脑组织含水量．组织切片苏木精一伊红染色观测炎性细胞浸润情况。结果外伤组与假手术对照组比较，ICAM—1蛋白表达分别于伤后6h明显升高．72h达到高峰（P〈0.05），ICAM—ImRNA表达3h即明显升高，72h达最高峰，其后下降。7d时仍高于假手术对照组（P〈0．01）。伤后脑组织含水量较假手术对照组高，同时炎性细胞大量聚集。结论大鼠脑外伤诱导了ICAM—1的表达．ICAM—1通过介导炎性细胞的浸润可能参与了伤后脑水肿的形成过程．     

The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury

The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-¹³C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using ¹H- and ¹³C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.     

Pathological reaction of astrocytes in perinatal brain injury

Summary Astrocytic reaction to various types of pre-and perinatal damage in the brain was studied using the immunohistochemical method for glial fibrillary acidic protein. The reactive gliosis could be detected as early as 20 weeks gestation. Reactive proliferation of the astrocytes could be seen already at 4 days after the insult. In addition to reacting to focal lesions, the astrocytes also proliferated diffusely throughout the white matter. The diffuse proliferation is the most significant finding in the evaluation of the perinatal damage, in both the acute state and in the long-term survivors.Supported in part by NIH Grant NS 06239. Part of the study was carried out while Dr. Roessmann was Visiting Professor at the University of Göttingen, supported by Deutsche Forschungsgemeinschaft, DFG-AZ: GO 76/100-1Presented in part at the IX International Congress of Neuropathology, Vienna, 1982     

大鼠海马区A1/A2型星形胶质细胞在弥漫性脑损伤后的表达变化

目的 检测大鼠在弥漫性脑损伤（DBI）后海马区 A1/A2 型星形胶质细胞（A1s、A2s）随时间 的表达变化。方法 选取 SD 雄性大鼠 48 只,随机分为对照组和 DBI 后 4 h、8 h、12 h、1 d、3 d、5 d、7 d 组, 每组6只,通过改良的Marmarou脑损伤打击装置建立大鼠脑损伤模型,通过大体观察、苏木素-伊红（HE） 染色观察大鼠脑组织损伤情况,通过免疫组织化学染色、实时荧光定量聚合酶链式反应（PCR）检测各组 大鼠海马区 A1s、A2s 标志物 C3d、S100A10 的蛋白及 mRNA 的表达变化。结果 大体观察显示,对照组 大鼠未见明显异常;实验组大鼠可见局限性蛛网膜下腔出血,侧脑室和脑组织腹侧面少量出血,脑组织 可见轻度水肿,未见局灶性脑挫伤及脑挫裂伤。HE 染色结果显示,实验组大鼠 DBI 后的大脑皮层及深 部脑组织形态学改变,大鼠颅脑损伤为弥漫性,DBI 造模成功。免疫组织化学染色结果显示,对照组大 鼠海马区 C3d 蛋白的平均光密度值为（0.002 6±0.000 3）,DBI 后 4 h 升高至（0.003 4±0.000 1）,于 DBI 后 1 d 达高峰,为（0.015 8±0.000 4）,染色程度加深,随后逐渐下降,7 d 时为（0.003 6±0.000 2）;DBI 后 8 h、 12 h、1 d、3 d、5 d 组大鼠的海马组织 C3d 蛋白的平均光密度值高于对照组,差异均有统计学意义（均P＜ 0.05）。对照组大鼠海马区S100A10蛋白的平均光密度值为（0.078 7±0.006 8）,DBI后4 h下降至（0.051 9± 0.002 1）,1 d 时最少,为（0.005 2±0.000 2）,随后上升,7 d 时为（0.034 6±0.001 8）;DBI 后 4 h、8 h、12 h、1 d、 3 d、5 d、7 d 组大鼠的海马组织 S100A10 蛋白的平均光密度值低于对照组,差异均有统计学意义（均P＜ 0.05）。实时荧光定量 PCR 检测结果显示,C3d 于 DBI 后 4 h 出现升高的趋势,8 h 左右达高峰,表达量为 （9.365 2±0.543 8）2-Δ △ Ct,随后逐渐下降;S100A10 在 DBI 4 h 后开始下降,8 h 左右表达量最低,表达量为 （0.446 9±0.007 8）2-Δ △ Ct,随后呈上升趋势。DBI 后 4 h、8 h、12 h、1 d、3 d、5 d、7 d 组大鼠的 C3d mRNA 表达量均高于对照组,DBI 后 4 h、8 h、3 d、5 d、7 d 组大鼠的 S100A10 mRNA 表达量均低于对照组,差异 均有统计学意义（均P＜0.05）。结论 DBI后7 d内A1s、A2s呈单峰表达的时序性变化规律,且趋势相反, 为 DBI 时间推断、临床用药及治疗提供一定的理论依据。     

ERK1/2信号通路在弥漫性脑损伤中激活规律的实验研究

目的探讨弥漫性脑损伤（DBI）中细胞外信号调节激酶1／2（ErtK1／2）信号传导通路激活的时空变化特征。方法参照Marmarou方法制作大鼠DBI模型，Westernblot法检测损伤脑组织磷酸化ERK1／2（pErtK1／2）蛋白的表达。免疫组织化学法检测pERK1／2阳性细胞在损伤脑组织不同区域的分布。结果大鼠DBI后脑组织pERK1／2表达显著增高，5min即达峰值，随即下降，但至12-24h又有回升，达到第二个峰值，并持续高水平表达至72h。DBI损伤后30min-3h主要见胞浆阳性染色，损伤后24h在胞核、胞浆均可见阳性染色，以胞核为主。pERK1／2免疫阳性细胞多见于脑皮质深层，其次为海马，室管膜和脉络丛也可见pERK1／2阳性染色。结论大鼠DBI后ERK1／2通路被迅速和持久激活，pERK1／2免疫阳性细胞多见于脑皮质深层，也可见于海马、室管膜和脉络丛。     

Temporospatial effects of acyl‐ghrelin on activation of astrocytes after ischaemic brain injury

The protective mechanisms of astrocyte signalling are based on the release of neurotrophic factors and the clearing of toxic substances in the early stages of cerebral ischaemia. However, astrocytes are also responsible for the detrimental effects that occur during the later stages of ischaemia, in which glial scars are formed, thereby impeding neural recovery. Acyl‐ghrelin has been found to be neuroprotective after stroke, although the influence of acyl‐ghrelin on astrocytes after ischaemic injury is yet to be clarified. In the present study, we used permanent middle cerebral arterial occlusion to establish a brain ischaemia model in vivo, as well as oxygen and glucose deprivation (OGD) to mimic ischaemic insults in vitro. We found that acyl‐ghrelin injection significantly increased the number of activated astrocytes in the peri‐infarct area at day 3 after brain ischaemia and decreased the number of activated astrocytes after day 9. Moreover, the expression of fibroblast growth factor 2 (FGF2) in the ischaemic hemisphere increased markedly after day 3, and i.c.v. injection of SU5402, an inhibitor of FGF2 signalling, abolished the suppression effects of acyl‐ghrelin on astrocyte activation in the peri‐infarct region during the later stages of ischaemia. The results from in vitro studies also showed the dual effect of acyl‐ghrelin on astrocyte viability. Acyl‐ghrelin increased the viability of uninjured astrocytes in an indirect way by stimulating the secretion from OGD‐injured astrocytes. It also inhibited the astrocyte viability in the presence of FGF2 in a dose‐dependent manner. Furthermore, the expression of acyl‐ghrelin receptors on astrocytes was increased after acyl‐ghrelin and FGF2 co‐treatment. In conclusion, acyl‐ghrelin promoted astrocyte activation in the early stages of ischaemia but suppressed the activation in later stages of ischaemic injury. These later effects were likely to be triggered by the increased expression of endogenous FGF2 after brain ischaemia.     

Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury

γ‐Secretase is an aspartyl protease composed of four proteins: presenilin (PS), nicastrin (Nct), APH1, and PEN2. These proteins assemble into a membrane complex that cleaves a variety of substrates within the transmembrane domain. The γ‐secretase cleavage products play an important role in various biological processes such as embryonic development and Alzheimer's disease (AD). The major role of γ‐secretase in brain pathology has been linked to AD and to the production of the amyloid β‐peptide. However, little is known about the possible role of γ‐secretase following acute brain insult. Here we examined by immunostaining the expression patterns of two γ‐secretase components, PS1 and Nct, in three paradigms of brain insult in mice: closed head injury, intracerebroventricular injection of LPS, and brain stabbing. Our results show that in naïve and sham‐injured brains expression of PS1 and Nct is restricted mainly to neurons. However, following insult, the expression of both proteins is also observed in nonneuronal cells, consisting of activated astrocytes and microglia. Furthermore, the proteins are coexpressed within the same astrocytes and microglia, implying that these cells exhibit an enhanced γ‐secretase activity following brain damage. In view of the important role played by astrocytes and microglia in brain disorders, our findings suggest that γ‐secretase may participate in brain damage and repair processes by regulating astrocyte and microglia activation and/or function. © 2008 Wiley‐Liss, Inc.     

ERK1/2信号途径对大鼠弥漫性脑创伤后神经细胞凋亡的调控机制

目的 探讨脑创伤后ERK1/2信号调控神经细胞凋亡的分子机制.方法 SD大鼠分为正常对照组、模型组、抑制剂U0126高、低剂量组.Marmarou's法制作弥漫性脑创伤模型.光镜下观察伤后神经细胞形态变化;免疫组化和Western Blot法检测伤后磷酸化ERK1/2水平和Bax表达;TUNEL法检测凋亡细胞.结果 与正常对照组比较,模型组海马区部分神经细胞出现变性坏死和凋亡改变,磷酸化ERK1/2、Bax表达增高,神经细胞凋亡数目增多(P<0.05);U0126治疗后,脑组织形态损伤程度、磷酸化ERK1/2和Bax表达、神经细胞凋亡数目回降,上述变化在U0126高剂量组中更为显著.结论 脑创伤后活化的ERK1/2信号通过调控Bax表达在神经细胞凋亡过程中发挥重要作用.     

Early loss of astrocytes after experimental traumatic brain injury

Neuronal-glial interactions are important for normal brain function and contribute to the maintenance of the brain's extracellular environment. Damage to glial cells following traumatic brain injury (TBI) could therefore be an important contributing factor to brain dysfunction and neuronal injury. We examined the early fate of astrocytes and neurons after TBI in rats. A total of 27 rats were euthanized at 0.5, 1, 2, 4, or 24 h after moderate lateral fluid percussion TBI or after sham TBI. Ipsilateral and contralateral hippocampi were examined in coronal sections from -2.12 to -4.80 mm relative to bregma. Adjacent sections were processed with markers for either astrocytes or degenerating neurons. Astrocytes were visualized using glial fibrillary acidic protein (GFAP) or glutamine synthetase immunohistochemistry. Neuronal degeneration was visualized using Fluoro-Jade (FJ) histofluorescence. At 30 min, there was a significant loss of GFAP immunoreactivity in ipsilateral hippocampal CA3 with some loss of normal astrocyte morphology in the remaining cells. The number of normal staining astrocytes decreased progressively over time with extensive astrocyte loss at 24 h. At 4 h, lightly stained FJ-positive neurons were scattered in the ipsilateral CA3. The intensity and number of FJ-positive neurons progressively increased over time with moderate numbers of degenerating neurons in the ipsilateral hippocampal CA3 evident at 24 h. We conclude that astrocyte loss occurs in the hippocampus early after TBI. The data suggest that loss of supporting glial cell may contribute to subsequent neuronal degeneration.     

Lack of NG2 exacerbates neurological outcome and modulates glial responses after traumatic brain injury

Traumatic brain injury (TBI) is a major cause of death and disability. The underlying pathophysiology is characterized by secondary processes including neuronal death and gliosis. To elucidate the role of the NG2 proteoglycan we investigated the response of NG2‐knockout mice (NG2‐KO) to TBI. Seven days after TBI behavioral analysis, brain damage volumetry and assessment of blood brain barrier integrity demonstrated an exacerbated response of NG2‐KO compared to wild‐type (WT) mice. Reactive astrocytes and expression of the reactive astrocyte and neurotoxicity marker Lcn2 (Lipocalin‐2) were increased in the perilesional brain tissue of NG2‐KO mice. In addition, microglia/macrophages with activated morphology were increased in number and mRNA expression of the M2 marker Arg1 (Arginase 1) was enhanced in NG2‐KO mice. While TBI‐induced expression of pro‐inflammatory cytokine genes was unchanged between genotypes, PCR array screening revealed a marked TBI‐induced up‐regulation of the C‐X‐C motif chemokine 13 gene Cxcl13 in NG2‐KO mice. CXCL13, known to attract immune cells to the inflamed brain, was expressed by activated perilesional microglia/macrophages seven days after TBI. Thirty days after TBI, NG2‐KO mice still exhibited more pronounced neurological deficits than WT mice, up‐regulation of Cxcl13, enhanced CD45+ leukocyte infiltration and a relative increase of activated Iba‐1+/CD45+ microglia/macrophages. Our study demonstrates that lack of NG2 exacerbates the neurological outcome after TBI and associates with abnormal activation of astrocytes, microglia/macrophages and increased leukocyte recruitment to the injured brain. These findings suggest that NG2 may counteract neurological deficits and adverse glial responses in TBI. GLIA 2016;64:507–523     

Activation of the Nrf2-ARE signal pathway after blast induced traumatic brain injury in mice

Background: Treatment of blast-induced traumatic brain injury (bTBI) has been hindered. Previous studies have demonstrated that oxidative stress may contribute to the pathophysiological process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway exhibits a protective effect after traumatic brain injury (TBI). This study explored whether the Nrf2-ARE pathway was activated in a modified bTBI mouse model.

Method: Mice were randomly divided into six groups: the 6?h, 1 d, 3 d, 7 d and 14 d after bTBI groups and a sham group. The protein levels of nuclear Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) were detected using western blot, and HO-1 and NQO1 mRNA levels were determined by real-time quantitative polymerase chain reaction. Moreover, HO-1 and Nrf2 were localized using histological staining.

Results: The protein level of the Nrf2-ARE pathway in the frontal lobe increased significantly in the 3 d after bTBI. The HO-1 and NQO1 mRNA levels also reached a peak in the frontal lobe 3 d after bTBI. The histological staining demonstrated higher expression of HO-1 in the frontal lobe and hippocampus 3 d after bTBI, when nuclear import of Nrf2 reached a peak in the frontal lobe.

Conclusions: bTBI activated the Nrf2-ARE signaling pathway in the brain. The peak activation time in the frontal lobe may be 3 d after injury, and activating the Nrf2 pathway could be a new direction for treatment.     

Changes in T .lymphocyte subsets after severe traumatic brain inJury

BACKGROUND： Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE： To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN： A comparative observation. SETTINGS： Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS： All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score （GCS） was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group （GCS ranged 14- 15 points）, including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS： （1） The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. （2） The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES： Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS： Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. （1） Changes of T lymphocyte subsets： At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group （t =2.77 - 3.26, P 〈 0.01）, and began to recover at 7 days, which were significantly different from those in the control group （t = 2.06 - 2.24, P 〈 0.05）, and generally recovered to the normal levels at 14 days （P 〉 0.05）. （2） Conditions of pulmonary infections： At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% （22/30）, 0, x2=37.29, P 〈 0.01]. CONCLUSION： Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period （within 7 days）, and they are easily to be accompanied by pulmonary infections.     

Changes in T lymphocyte subsets after severe traumatic brain injury

BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN: A comparative observation. SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16–62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14–15 points), including 18 males and 12 females, aging 15–58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury. Informed consents were obtained from all the patients or their relatives. METHODS: ① The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at 1, 3, 7 and 14 days after injury in both groups. ② The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1–14 days after severe and mild or moderate traumatic injury. RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. ① Changes of T lymphocyte subsets: At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77–3.26, P < 0.01), and began to recover at 7 days, which were significantly different from those in the control group (t = 2.06–2.24, P < 0.05), and generally recovered to the normal levels at 14 days (P > 0.05). ② Conditions of pulmonary infections: At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% (22/30), 0, χ2=37.29, P < 0.01]. CONCLUSION: Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period (within 7 days), and they are easily to be accompanied by pulmonary infections.     

Distinctive responses of brain tumor cells to TLR2 ligands:

Malignant brain tumor mass contains significant numbers of infiltrating glial cells that may intimately interact with tumor cells and influence cancer treatments. Understanding of characteristic discrepancies between normal GLIA and tumor cells would, therefore, be valuable for improving anticancer therapeutics. Here, we report distinct differences in toll‐like receptors (TLR)?2‐mediated responses between normal glia and primary brain tumor cell lines. We found that tyrosine phosphorylation of STAT1 by TLR2 ligands and its downstream events did not occur in mouse, rat, or human brain tumor cell lines, but were markedly induced in normal primary microglia and astrocytes. Using TLR2‐deficient, interferon (IFN)‐γ‐deficient, and IFNγ‐receptor‐1‐deficient mice, we revealed that the impaired phosphorylation of STAT1 might be linked with defective TLR2 system in tumor cells, and that a TLR2‐dependent pathway, not IFNγ‐receptor machinery, might be critical for tyrosine STAT1 phosphorylation by TLR2 ligands. We also found that TLR2 and its heterodimeric partners, TLR1 and 6, on brain tumor cells failed to properly respond to TLR2 ligands, and representative TLR2‐dependent cellular events, such as inflammatory responses and cell death, were not detected in brain tumor cells. Similar results were obtained in in vitro and in vivo experiments using orthotopic mouse and rat brain tumor models. Collectively, these results suggest that primary brain tumor cells may exhibit a distinctive dysfunction of TLR2‐associated responses, resulting in abnormal signaling and cellular events. Careful targeting of this distinctive property could serve as the basis for effective therapeutic approaches against primary brain tumors. GLIA 2015;63:894–905     

Neuroimaging correlates of anxiety after pediatric traumatic brain injury.

BACKGROUND: Anxiety disorders are common after traumatic brain injury (TBI). Data on the neural correlates of these conditions are lacking. This study examines the relationship between brain damage, particularly to the orbitofrontal cortex (OFC) and temporal lobe, and anxiety symptoms and disorders. METHODS: Ninety-five children and adolescents were followed for one year postinjury. Preinjury and one-year postinjury anxiety status were obtained from the parent. Magnetic resonance imaging was performed to evaluate brain lesions. The primary analysis used regression models to determine relationships between brain lesions and anxiety outcomes. As a secondary analysis, previously reported posttraumatic stress disorder (PTSD) data were reanalyzed using similar methods for purposes of comparison. RESULTS: The primary analysis showed that greater volume and number of OFC lesions correlated with decreased risk for anxiety, whereas lesions in other brain areas did not correlate with anxiety. Consistent with prior data, the secondary analysis showed an inverse correlation between OFC damage and PTSD; temporal lobe damage was positively correlated with PTSD. CONCLUSIONS: After pediatric TBI, greater damage to the OFC is associated with decreased risk for anxiety outcomes. Similar to adult data, these findings implicate OFC dysfunction in childhood anxiety. Temporal lobe damage did not correlate with anxiety, in contrast to the findings for PTSD.     

大鼠轻型颅脑损伤后星形胶质细胞与神经元的病理改变

目的 探讨轻型颅脑损伤（TBI）后神经元及星形胶质细胞改变的病理生理过程。方法 将24只成年SD大鼠随机分为轻型TBI组（n=18）和假手术组（n=6）,轻型TBI组又分为伤后3 h（n=6）、伤后24 h（n=6）、伤后72 h（n=6）三亚组。采用液压冲击法制作轻型TBI模型。采用胶质纤维酸性蛋白（GFAP）染色检测星形胶质细胞,采用Fluoro-Jade B（FJ-B）荧光染色检测变性神经元。结果 与假手术组相比,轻型TBI后3 h、24 h、72 h邻近顶叶皮质、海马CA2/3区GFAP阳性细胞数量均明显减少（P<0.05）;缺失区周围星形胶质细胞肿胀增生明显。FJ-B阳性神经元在损伤后3 h无明显增加（P>0.05）,伤后24 h皮层区FJ-B阳性神经元显著增加（P<0.05）,伤后72 h海马区FJ-B阳性神经元显著增加（P<0.05）。伤后72 h伤侧皮层区与海马区GFAP阳性细胞数和FJ-B阳性细胞数呈显著负相关（r=-0.8285,P<0.05）。结论 轻型TBI后星形胶质细胞超急性期（3 h）即出现损害和胶质反应,神经元则在急性期（24 h）至亚急性期（72 h）出现明显损害,星形胶质细胞缺失程度可以反应神经元损伤程度。