鼠脑液压伤后血脑屏障通透性变化对磷脂酶A_2和脑水肿的影响

目的：研究颅脑损伤早期血脑屏障通透性（ＢＢＢＰ）、磷脂酶Ａ２（ＰＬＡ２）与脑水肿的改变及其相关关系；以及地塞米松和尼莫地平治疗的影响。方法：应用鼠脑液压伤模型，观测伤后不同时间伊文氏蓝在伤侧脑组织内吸光度变化、ＰＬＡ２和脑含水量改变；并观测经腹腔注射地塞米松和尼莫地平后上述指标的改变。结果：液压伤后１小时伤侧脑组织伊文氏蓝吸光度开始升高，伤后６小时至峰值，随后逐渐降低，伤后１２小时～７２小时仍维持在高于对照组１倍以上的水平；ＰＬＡ２于液压伤后１小时发生改变，１２小时～２４小时达峰值，４８小时～７２小时仍高于对照组；脑含水量在伤后２４小时～７２小时呈阶梯状升高；创伤早期ＢＢＢＰ的改变程度较ＰＬＡ２和脑含水量明显；ＢＢＢＰ与ＰＬＡ２和脑含水量均呈正相关。结论：①创伤早期ＢＢＢＰ增加是由脑血管功能紊乱和机械物理损伤所致，也是ＰＬＡ２升高和血管源性脑水肿形成的诱因；②创伤后２４小时～７２小时ＰＬＡ２的升高，导致细胞毒性脑水肿，促使血脑屏障结构破坏，ＢＢＢＰ增加，脑继发性损伤加重，３者间呈互相增强作用；③早期应用大剂量地塞米松和尼莫地平治疗对抑制ＰＬＡ２的活性。

FK506对大鼠脑液压伤后神经行为和记忆的影响

目的 研究FK506对大鼠脑液压伤后神经行为和记忆的影响。方法 通过液压损伤法建立大鼠脑损伤模型,随机分为损伤组、治疗组和对照组(每组8只)。采用免疫组化方法和图象分析技术,检测突触素在皮质、海马和基底节的表达,并用流式细胞仪法检测上述部位的凋亡细胞数。结果 治疗组神经行为与记忆实验成绩高于损伤组。治疗组海马CA1、CA3区突触素表达显著增高(P<0.01)。海马、基底节和皮质的凋亡细胞数较损伤组明显减少。结论 FK506能促进突触素表达,减少海马和皮质细胞凋亡,有利于促进脑损伤后神经行为和记忆的恢复。

神经节苷脂GM_1对大鼠脑液压伤后行为和记忆的影响

目的 :探讨大鼠脑液压伤后GM1与学习记忆、脑内一氧化氮、突触素和细胞凋亡的关系。方法 :液压损伤法建立大鼠脑损伤模型 ,随机分为治疗组、损伤组和对照组。观察伤后学习记忆改变 ,检测一氧化氮合酶 (NOS)、一氧化氮 (NO)、突触素和海马、皮质及基底节区细胞凋亡指数。结果 :治疗组学习记忆成绩高于损伤组 ,NOS、NO明显降低 ,治疗组海马CA1区突触素显著增多 ,皮质、海马和基底节的凋亡细胞数明显减少。结论 :GM1能减少海马和皮质细胞凋亡 ,可能有利于促进脑损伤后神经行为和记忆的恢复。

Changes in and effective factors of microtubule associated protein 2 in traumatic neurons

Objective To investigate alterations in the microtubule-associated protein 2 (MAP-2) of neurons in Wistar rats and the effect of nimodipine (Nim), D-2-amino-5-phosphonovaleric acid (D-AP-5) and mild hypothermia on neuronal MAP-2 following fluid percussion injury (FPI).Methods Alterations of MAP-2 in Wistar rat neurons following FPI were measured by a confocal laserscanning microscope using MAP-2 immunofluorescence staining as a MAP-2 indicator.Results MAP-2 immunofluorescence staining was limited to the cell bodies and dendritic compartments of neurons and more intense in dendrites than in cell bodies. The loss of MAP-2 was marked at 3 h posttrauma ( P ＜ 0.01 ), and reached a maximum at 48 h post-trauma. Afterwards, fluorescence recovered partly at 72 h post-trauma. The application of Nim markedly reduced the loss of MAP-2 immunoreectivity within 1 h post-trauma ( P ＜ 0.01 ), and the application of D-AP-5 markedly reduced the loss of MAP-2immunoreactivity within 10 h post-injury ( P ＜ 0.01 ). The application of mild hypothermia decreased the loss of MAP-2 immunoreactivity within 1 h post-injury (P＜ 0.05).Conclusions The partial recovery of fluorescence at 72 h post-trauma indicate that the partial structure of the neuronal microtubules can be repaired by itself. Nim, D-AP-5 and mild hypothermia reduce the degradation of MAP-2 by different mechanisms. The treatment of neuronal cytoskeleton degradation following FPI must employ multiple therapeutic approaches.

Spatial and temporal profile of apoptosis following lateral fluid percussion brain injury

Objective: To investigate the spatial and temporal profile of neural cell apoptosis following traumatic brain injury (TBI). Methods: In addition to morphological evidence of apoptosis, TUNEL histochemistry assay was used to identify DNA fragmentation in situ at both light and electron microscopic levels, whereas characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. Results: Using TUNEL method, we detected massive cells with extensive DNA fragmentation in different regions of the brains of rats subjected to experimental traumatic brain injury. Compared with the sham controls, in the injured cortex, the apoptotic cells were detectable for up to 24 h and reached a peak at 1 week after injury. The number of apoptotic cells in the white matter had a significant increase as early as 12 h after injury and peaked at 1 week. The number of apoptotic cells increased in the hippocampus at 72 h, whereas in the thalamus, the peak of apoptotic cells was at 2 weeks after injury. The number of apoptotic cells in most regions returned to sham values 2 months after injury. Gel electrophoresis of DNA extracted from affected areas of the injured brain revealed only internucleosomal fragmentation at 185-bp intervals, a feature originally described in apoptotic cell death. And no DNA ladder was detectable in the cortex and hippocampus contralateral to the injured hemisphere.Conclusions: These data suggest that in addition to the well described necrotic cell death, a temporal course of apoptotic cell death is initiated after brain trauma in selected brain regions.

Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage

Objective： To investigate the changes and effects of arginine vasopressin （AVP） in patients with acute traumatic subarachnoid hemorrhage （tSAH）. Methods： The plasma and cerebrospinal fluid （CSF） level of AVP, and intracranial pressure （ICP） were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale （GCS）. Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group. Results： Compared with control group, the levels （pg/ml） of AVP in plasma and CSF （x±s） in tSAH group were significantly increased within 24 hours （38.72±24.71 vs 4.54±1.38 and 34.61±21.43 vs 4.13± 1.26, P〈0.01）, and was remarkably higher in GCS ≤8 group than GCS〉8 group （50.96±36.81 vs 25.26±12.87 and 44.68±31.72 vs 23.53±10.94, P〈0.05）. The CSF AVP level was correlated with ICP （r= 0.46, P〈0.05）, but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS （r= -0.29, P〉0.05 and r= -0.32, P〉0.05, respectively）. The ICP （ram Hg） in tSAH patients was elevated and higher in GCS ≤ 8 group than in GCS〉8 group （25.9±9.7 vs 17.6±5.2, P〈0.05）. Conclusion： Our research suggests that AVP is correlated with the severity oftSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity oftSAH.