高原大鼠颅脑损伤局部脑组织氧分压变化特点

目的建立模拟高原条件下大鼠开放性颅脑损伤的实验模型,探讨模拟高原颅脑战伤伤情特点,为高原颅脑战伤救治提供实验依据.方法通过民用射钉枪射击建立大鼠开放性颅脑损伤的模型;通过低压氧舱模拟高原条件,并与正常平原环境条件下对照,观察模型的伤情特点;应用LICOX CMP组织氧监测仪进行局部脑组织氧分压动态监测.结果本实验条件下所制备的大鼠开放性颅脑损伤模型,伤情稳定,可重复性好;局部脑组织氧分压于伤后1 h开始明显下降,在伤后24～48 h下降到最低,之后开始恢复;高原对照组与平原对照组相比,局部脑组织氧分压无明显差异,在伤后1 h仍无明显差异,在伤后6～72 h高原组则明显低于平原组.结论通过民用射钉枪射击致伤,并结合低压氧舱持续减压,可以成功建立模拟高原条件下大鼠低速低能投射物所致的开放性颅脑损伤模型;与平原对照组相比,高原缺氧对照组大鼠局部脑组织氧分压无明显变化,但模拟高原条件下开放性颅脑损伤伤后伤区局部脑组织缺氧下降更为严重、持续时间更长,表明局部脑组织氧分压监测能较好地反映颅脑损伤后缺血缺氧状态,尤其在高原缺氧环境下更具有特殊重要意义.     

银杏叶提取物对大鼠创伤后脑细胞的保护作用

目的探讨银杏内酯对创伤性脑损伤（TBI）后神经细胞及其功能的保护作用。方法按自由落体撞击法造成TBI模型，通过木条平衡实验评价伤后大鼠的神经功能恢复情况，并在伤后不同时间点观察病理改变，同时检测脑组织中丙二醛（MDA）、NO和水含量的改变。结果与假损伤组比，伤后第一天大鼠脑组织内MDA和NO的含量显著升高（P〈0.01），不同时间点脑组织的含水量显著增加（P〈0.01），伤后1周内大鼠完成木条平衡作业的能力明显受损（P〈0.05）。经银杏内酯治疗后，TBI大鼠神经功能明显改善，病理改变减轻，脑组织含水量及MDA、NO的含量明显降低。结论银杏内酯可以促进颅脑损伤后神经功能的恢复，可能与早期抗氧化应激、降低NO的产生、减轻脑水肿、保护脑组织有关。     

模拟高原条件下大鼠爆炸性颅脑创伤伤情特点的研究

目的建立模拟高原条件下大鼠爆炸性颅脑外伤的动物模型，研究其伤情特点。方法用动物低压氧舱模拟高原环境，设计实验用大鼠爆炸性颅脑创伤实验舱，运用8#军用雷管，爆心距离目标18cm，建立大鼠爆炸性颅脑创伤的模型，观察该模型的动物行为学、病理学、脑含水量、血脑屏障开放程度和脑组织氧分压等结果，认识高原开放性颅脑创伤伤情特点。结果本实验制备的爆炸性颅脑创伤动物模型，伤情稳定，可重复性好；高原致伤组与平原致伤组均存在：（1）病理检查发现神经元细胞核、尼氏体和细胞器出现不同程度的损伤及缺血性改变。（2）脑含水量测定提示存在脑水肿。（3）伊文思蓝荧光染料示踪血脑屏障通透性存在不同程度的血脑屏障开放。（4）激光多普勒脑血流及脑组织氧分压监测提示脑组织局部缺血缺氧表现，两组比较，高原致伤组上述结果更严重，持续时间更长。结论本实验制备的动物模型，可以模拟高原环境的爆炸性颅脑创伤，高原致伤组与平原致伤组比较，其损伤程度更严重，持续时间更长。     

抑制NKCC1减轻小鼠创伤性脑损伤的研究

目的探讨钠．钾-氯共转运体1（Na＋-K＋-2C1-cotransporter1,NKCCl）抑制剂布美他尼处理（BT）对小鼠创伤性脑损伤（TBI）早期的脑保护作用及可能分子信号调控机制。方法成年雄性BALB／c小鼠54只,随机分为对照组,颅脑创伤组（TBI组）和布美他尼治疗组（B1Tr组）各18只,采用Mamarou加速性颅脑损伤方法制备小鼠TBI模型。采用HE染色法观察各组小鼠皮层损伤程度;利用神经功能学评分（NSS）进行神经功能学评分;干湿重法检测脑组织含水量;同时,Westernblot法检测磷酸化细胞外调节蛋白激酶（p-ERK）、细胞外调节蛋白激酶（ERK）蛋白的表达变化。结果与TBI组比较,BTT组皮层神经元损伤减轻,同时,BTT组小鼠神经功能学评分优于TBI组（P〈0．05）;TBI后12h,BTT组p-ERK的蛋白表达水平低于TBI组（P〈0．01）。结论抑制NKCC1的表达可能发挥重要的脑保护作用,而p-ERK可能参与NKCC1的信号调控机制。     

颅脑损伤程度对大鼠脑血流及氧代谢的影响

目的 对颅脑损伤影响脑血流及氧代谢进行前瞻性研究。方法 30只Wistar大白鼠分成3组：颅脑损伤1组（TBI1）、2组（TBI2）及3组（TBI3）各10只，分别为轻、中、重型颅脑损伤。用脑阻抗（REG）测定脑血流量，颈内静脉血氧饱和度（SjVO2)反映全脑氧代谢情况。结果 TBI、TBI2及TBI3组影响脑血流和氧代谢程度依次为TBI3＞TBI2＞TBI1，健侧脑组织含水量各组无明显差异，伤侧脑组织含水量TBI3组最多，其次为TBI2，明显高于TBI1组（P＜0．01）。结论 颅脑损伤后脑血流和氧代谢变化取决于损伤程度，脑血流和氧代谢各参数的监测对正确认识脑组织病理生理变化，指导临床治疗，判断预后有重要价值。     

高压氧对颅脑损伤患者认知功能障碍恢复的影响

目的观察高压氧对颅脑损伤患者认知功能障碍恢复的临床疗效。方法随机抽取颅脑损伤患者80名,在常规治疗的基础上行高压氧治疗。观察治疗前后神经功能、血液流变学及认知功能的变化,认知功能检查采用简易精神状态检查表（MMSE）、数字广度测验（DST）、日常生活能力（ADL）、汉密尔顿抑郁量表（HAMD）等神经心理学检查法,结果与对照组进行比较。结果治疗组神经功能、血液流变学及认知功能障碍较治疗前明显改善（P〈0.01）,与对照组比较亦有显著性差异（P〈0.01）。结论高压氧对颅脑损伤患者的脑组织有保护作用,能显著改善颅脑损伤患者认知功能障碍。     

红景天苷对大鼠颅脑损伤的保护作用研究

目的探讨红景天苷(Salidroside,Sal)对大鼠颅脑外伤的神经保护作用及其机制。方法健康成年SD大鼠36只,随机分为3组:假手术组(Sham组)、对照组(TBI组)、Sal给药组(TBI+Sal组)。通过Feeney's自由落体打击法制作大鼠颅脑损伤模型,24 h后对大鼠神经功能损伤评分,对神经元行尼氏(Nissl)染色,检测动物损伤脑组织中GSH、SOD及MDA的水平,Tunel染色检测细胞凋亡。结果 TBI+Sal组较TBI组,降低了神经功能缺损评分、细胞凋亡数量、MDA水平,显著增加了Nissl阳性细胞的数量、SOD的活性以及GSH的水平。结论 Sal能减轻大鼠TBI后神经功能缺损,具有神经保护作用,此作用依赖于抗氧化及抗凋亡的作用机制。     

香芹酚通过抑制脑水肿与氧化应激反应保护大鼠 颅脑损伤

目的 探讨香芹酚对大鼠颅脑损伤（TBI）的保护作用及其机制。方法 SD大鼠50只,随机分为5组:假手术组、模型组、低剂量香芹酚（10 mg/kg）组、中剂量香芹酚（20 mg/kg）组、高剂量香芹酚（40 mg/kg）组,每组10只。Feeney氏自由落体法制备TBI模型,造模后1、3、7 d采用改良神经功能损害程度评分（mNSS）评估神经功能,干湿法测定脑组织含水量;ELISA法检测氧化应激因子丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、过氧化氢酶（CAT）以及化学定量法检测一氧化氮（NO）含量及一氧化氮合酶（NOS）活性。结果 香芹酚能显著改善大鼠TBI后神经功能,显著减轻TBI后脑水肿,显著降低损伤脑组织MDA、NO和NOS含量,显著增加损伤脑组织SOD、CAT和GSH含量。结论 香芹酚可通过减轻大鼠TBI后脑水肿、抑制氧化应激从而发挥神经保护作用。     

神经干细胞立体定向脑内移植治疗大鼠重型颅脑损伤

目的探讨神经干细胞立体定向脑内移植对颅脑损伤大鼠的治疗效果。方法采用Feeney等人的方法制成大鼠脑损伤模型,伤后24h将体外培养的胚胎神经干细胞经立体定向移植到脑损伤灶内。伤前24h、伤后24h及伤后1、2周行动物神经学缺损评分。结果移植后1和2周,接受神经干细胞移植的大鼠神经学缺损评分明显低于对照组（P〈0.05）;且其脑组织切片中的神经元数量较对照组明显增多（P〈0.01）。结论经立体定向移植到脑内损伤灶的神经干细胞可存活、增殖、分化、并可明显改善重型颅脑损伤后大鼠的神经学功能。     

高压氧联合纳洛酮治疗重型颅脑损伤疗效分析

目的观察高压氧联合纳洛酮治疗重型颅脑损伤（STBI）的临床疗效。方法将60例重型颅脑损伤患者按治疗方法不同随机分为对照组和观察组各30例,对照组给予常规治疗,观察组在常规治疗基础上加用纳洛酮静滴和高压氧治疗,观察2组治疗前后GCS评分及伤后3个月GOS评分改善情况。结果与治疗前比较,2组患者治疗14dGCS评分均优于治疗前,且观察组GCS评分改善优于对照组（P〈0.05）;观察组患者治疗3个月后临床疗效明显优于对照组,差异有统计学意义（P〈0.05）。结论高压氧联合纳洛酮治疗重型颅脑损伤患者可提高临床疗效,促进神经功能恢复,改善预后和提高患者生存质量,值得临床推广应用。     

Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury：not by immediately improving cerebral oxygen saturation and oxygen partial pressure

Although hyperbaric oxygen (HBO) therapy can promote the recovery of neural function in patients who have suffered traumatic brain injury (TBI), the underlying mechanism is unclear. We hypothesized that hyperbaric oxygen treatment plays a neuroprotective role in TBI by increasing regional transcranial oxygen saturation (rSO2) and oxygen partial pressure (PaO2). To test this idea, we compared two groups:a control group with 20 healthy people and a treatment group with 40 TBI patients. The 40 patients were given 100% oxygen of HBO for 90 minutes. Changes in rSO2 were measured. The controls were also examined for rSO2 and PaO2, but received no treatment. rSO2 levels in the patients did not differ signiifcantly after treatment, but levels before and after treatment were signiifcantly lower than those in the control group. PaO2 levels were signiifcantly decreased after the 30-minute HBO treatment. Our ifndings suggest that there is a disorder of oxygen metabolism in patients with sub-acute TBI. HBO does not immediately affect cerebral oxygen metabolism, and the underlying mechanism still needs to be studied in depth.     

Evaluation of the apoptosis-related proteins of the BCL-2 family In the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study

The growth and progression of traumatic brain injury (TBI) lesions depend significantly on developments in the traumatic penumbra area, perilesional region, where delayed neuronal death occurs. Recent data supports the important role of apoptosis in delayed cell death in TBI. Previously we demonstrated a significant reduction of apoptosis in traumatic penumbra in animals treated by hyperbaric oxygen (HBO).In this study we evaluate the expression of apoptosis-related proteins of the Bcl-2 family (Bcl-2, Bax and Bcl-xL) in the traumatic penumbra area in correlation with the extent of apoptosis in the rat model of focal cerebral contusion, treated by HBO. Sprague-Dawley rats underwent cortical dynamic deformation, some with subsequent hypoxemia. A group of both hypoxemic and non-hypoxemic animals was treated by HBO. The pathological study was based on immunohistochemical staining of the brain sections for Bcl-2, Bax and Bcl-xL with quantitative evaluation of staining by image analysis. The expression of Bcl-2 in hypoxemic animals was lower than in non-hypoxemic animals, but a significant increase in Bcl-2 expression was seen in both groups after HBO treatment. Bcl-xL also demonstrated an increase after HBO treatment but less significant. Staining for Bax protein did not demonstrate significant change after treatment. These data correlate well with the reduction of TUNEL-positive cells in traumatic penumbra after HBO treatment. We concluded that the apoptotic mechanisms are important in delayed cell death in TBI and that post-traumatic hypoxemia increases the intensity of apoptosis, probably through a decrease in Bcl-2 and Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO treatment in our model of brain contusion correlates well with the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and the appropriate decrease in the extent of apoptosis. In light of these results, the usage of HBO is justified as neuroprotective treament in TBI.     

高压氧预处理可对大鼠局灶性脑缺血再灌注损伤的保护作用

目的研究短期高压氧预处理后是否可减轻大鼠局灶性脑缺血再灌注损伤。方法选取成年雄性Wister大鼠,采用连续5d,每天1次,3.0ATA,100%O2高压氧(HBO)预处理,每次60min,末次预处理后24h,运用改良的经典线栓法制作MCAO模型,再灌注2h。将实验大鼠分为假手术组、MCAO组、HBO+MCAO组(n=5)。造模后24h观察各组动物的一般精神状态及体重变化情况、用Rogers DC and Hunter AJ描述的神经功能7分评分法对神经功能损伤进行评估,TTC染色测梗死面积,并对脑组织进行石蜡切片,行Nissl、TUNEL染色,利用显微镜对神经细胞进行计数。结果假手术组无神经功能缺失,TTC染色未见梗死灶,镜下观察未见坏死细胞。MCAO组和HBO+MCAO组均有不同程度的神经功能缺损,且HBO+MCAO组神经功能缺失较MCAO组轻;TTC染色MCAO组的梗死面积明显大于HBO+MCAO组;镜下观察,MCAO组梗死区内尼氏小体明显少于HBO+MCAO组。结论短期高压氧预处理后可减轻大鼠局灶性脑缺血再灌注损伤。     

丁苯酞预处理对大鼠脑缺血再灌注损伤的神经保护作用

目的研究丁苯酞预处理对大鼠局灶性脑缺血再灌注损伤的神经保护作用。方法健康成年SD雄性大鼠48只,随机分为假手术组、缺血再灌注组、丁苯酞预处理组,每组各16只。各组均灌胃5d后,采用线栓法制作大鼠局灶性脑缺血再灌注(MCAO)模型,缺血2h、再灌注24h,进行神经功能缺损评分,TTC染色及图像分析观察脑梗死体积,免疫组化法检测脑组织caspase-3、bcl-2表达的变化。结果与缺血再灌注组相比,丁苯酞预处理组神经缺损程度改善,梗死灶体积减少,caspase-3阳性细胞数量减少,bcl-2表达上调。结论丁苯酞可减轻缺血性脑血管病的发作,具有一定的神经保护作用。     

缺氧预处理对颅脑损伤大鼠脑组织HIF-1α及其HO-1表达的影响

目的探讨缺氧预处理对颅脑损伤大鼠脑组织缺氧诱导因子（HIF-1α）及血红素氧合酶-1（HO-1）表达的影响。方法 Sprague-Dawley大鼠102只,随机分为对照组（n=6）、创伤组（n=48）和预处理组（n=48）。创伤组按照改进的Feeney自由落体撞击法建立大鼠颅脑损伤模型,预处理组给予缺氧预处理后,同法造模。采用RT-PCR和Western blotting观察伤后1 h、4 h、8 h、12 h和1 d、3 d、7 d、14 d挫伤周围脑组织HIF-1α、HO-1表达变化。结果创伤组与对照组比较,HIF-1α和HO-1在伤后4 h、8 h、12 h和1、3 d表达上调（P〈0.05）。预处理组与创伤组比较,HIF-1α和HO-1在伤后1 h逐渐上调,伤后4 h、8 h、12 h和1、3 d表达显著上调,直至伤后7 d（P〈0.05）。结论缺氧预处理可增加颅脑损伤后挫伤区周围脑组织HIF-1α的表达,进而促进HO-1 m RNA及蛋白表达。其机制可能是缺氧预处理提高颅脑损伤对缺氧的适应性,减轻挫伤周围脑组织氧自由基对神经细胞伤害。     

高压氧治疗大鼠脑外伤后脑组织NF-κB(P50)表达的实验研究

目的 探讨高压氧对颅脑外伤的治疗作用及与脑组织中NF-κB(P50)表达之间的关系. 方法 120只SD大鼠按随机数字表法分为假手术组(仅开颅钻孔,不行打击)、外伤对照组(Feeney自由落体损伤模型制作法制造中度大鼠脑外伤模型,但不接受氧治疗)、常压氧治疗组(脑外伤模型制作成功后立即接受正常压力下纯氧吸入治疗)、高压氧治疗组(脑外伤模型制作成功后立即接受0.2 MPa压力下高压氧治疗),并于伤后6h、1 d、3 d、5 d、7 d五个时相点断头法取脑组织(每时相点6只),光镜下观察脑组织损伤水肿的病理变化以及采用免疫组化方法检测NF-κB(P50)在脑组织中的表达情况. 结果 高压氧干预使相同时相点高压氧治疗组大鼠脑水肿情况及损伤程度较外伤对照组明显减轻,而常压氧干预作用则不明显.假手术组各时相点仅见微量的NF-κB(P50)阳性表达或不表达,其他各组脑损伤后6 h即发现损伤脑组织内NF-κB(P50)阳性表达上调,且持续呈增高趋势,伤后5 d时达到最高值.高压氧治疗组与外伤对照组及常压氧治疗组相比在相同时相点NF-κB(P50)表达均有增强,差异有统计学意义(P<0.05). 结论 高压氧治疗对损伤神经细胞具有保护、修复的治疗作用,增加NF-κB(P50)在脑组织细胞中的表达可能是其神经保护途径之一.     

Hyperbaric oxygen in traumatic brain injury

OBJECTIVES: This critical literature review examines historical and current investigations on the efficacy and mechanisms of hyperbaric oxygen (HBO) treatment in traumatic brain injury (TBI). Potential safety risks and oxygen toxicity, as well as HBO's future potential, are also discussed. METHODS: Directed literature review. RESULTS: Historically, cerebral vasoconstriction and increased oxygen availability were seen as the primary mechanisms of HBO in TBI. HBO now appears to be improving cerebral aerobic metabolism at a cellular level, namely, by enhancing damaged mitochondrial recovery. HBO given at the ideal treatment paradigm, 1.5 ATA for 60 minutes, does not appear to produce oxygen toxicity and is relatively safe. DISCUSSION: The use of HBO in TBI remains controversial. Growing evidence, however, shows that HBO may be a potential treatment for patients with severe brain injury. Further investigations, including a multicenter prospective randomized clinical trial, will be required to definitively define the role of HBO in severe TBI.     

The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia

We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.