Magnesium gluconate offers no more protection than magnesium sulphate following diffuse traumatic brain injury in rats

OBJECTIVE: Previous studies have demonstrated that magnesium salts, including the sulphate and chloride forms, are neuroprotective following traumatic brain injury (TBI). Recently, studies in cardiac ischaemia/reperfusion injury have demonstrated that the gluconate salt of magnesium may provide superior protection against oxidative damage and postischaemic dysfunction than MgSO(4). We have therefore compared the efficacy of both MgSO(4) and magnesium gluconate (MgGl(2)) on outcome following diffuse TBI in rats. METHODS: Adult male Sprague-Dawley rats were injured using the 2-metre impact acceleration model of diffuse TBI. At 30 min after injury, animals were administered with either 250 micromoles/kg i.v. MgSO(4), MgGl(2), or equal volume saline vehicle. Thereafter, animals were assessed for motor and cognitive outcome using the rotarod and Barnes maze, respectively, or their brains removed at 3 days after TBI and used for histological examination. RESULTS: Treatment with either magnesium salt significantly improved functional outcome as compared to vehicle treated controls. Similarly, treatment with either magnesium salt attenuated the degree of histological dark cell change at 3 days after TBI relative to the vehicle treated animals. There were no significant differences between the magnesium treated groups. CONCLUSIONS: We conclude that MgSO(4) and MgGl(2) are equally neuroprotective following TBI. Our results suggest that MgGl(2) may only be more effective in conditions that produce ischaemia, where high concentrations of reactive oxygen species are generated.     

A substance P antagonist increases brain intracellular free magnesium concentration after diffuse traumatic brain injury in rats

OBJECTIVE: Magnesium (Mg) deficiency has been shown to increase substance P release and induce a pro-inflammatory response that can be attenuated with the administration of a substance P-antagonist. Neurogenic inflammation has also been implicated in traumatic brain injury (TBI), a condition where brain intracellular free magnesium (Mg(f)) decline is known to occur and has been correlated with functional outcome. We therefore examined whether a substance P antagonist restores brain intracellular free magnesium concentration following TBI. METHODS: Male, adult Sprague-Dawley rats were injured using the Cernak impact acceleration model of diffuse TBI. At 30 min after injury, animals were administered either 0.25 mg/kg i.v. n-acetyl tryptophan or equal volume saline. Prior to and 4 h after induction of injury, phosphorus magnetic resonance spectra were acquired using a 7-tesla magnet interfaced with a Bruker console. Mg(f) was calculated from the chemical shift of the beta ATP. Before injury, Mg(f) was 0.51 +/- 0.05 mM (SEM). RESULTS: By 4 hr after injury, Mg(f) had significantly declined to 0.27 +/- 0.02 mM in saline treated rats. In contrast, rats treated with n-acetyl tryptophan had a Mg(f) of 0.47 +/- 0.06 mM at 4 h after injury, which was not significantly different from preinjury values. There were no significant differences in pH between the treatment groups. CONCLUSION: It seems that any beneficial effect of a substance P antagonist on functional outcome following TBI may be related to improvement in brain Mg homeostasis induced by the compound.     

ω-3多不饱和脂肪酸抑制大鼠创伤性脑损伤后小胶质细胞介导的炎症反应

目的　研究ω-3多不饱和脂肪酸对大鼠创伤性脑损伤(TBI)后神经细胞凋亡、脑水肿、小胶质细胞活化、炎症反应及神经功能的影响,以探讨ω-3多不饱和脂肪酸对大鼠TBI的保护及机制。方法　采用改良Feeney DM法建立大鼠TBI模型,将90只SD大鼠完全随机分为假手术组（Sham组）,TBI组,TBI+c-Jun氨基末端激酶（JNK）选择性激活剂 anisomycin组（TBI+Aniso组）;TBI+ω-3多不饱和脂肪酸组（TBI+ω-3组）,TBI+ω-3多不饱和脂肪酸+JNK选择性激活剂 anisomycin组（TBI+ω-3+Aniso组）,分别于伤后1、3、7 d进行神经行为学评分（mNSS）;采用干湿重法测损伤区脑组织脑水含量;TUNEL和免疫荧光等方法测定细胞凋亡和小胶质细胞活化特异标志物IBA-1的表达;PCR、Westerrn blot等检查脑组织炎症因子肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1α、IL-1β、IL-6及上游JNK信号通路JNK、p-JNK分子表达水平的变化。结果　与同期Sham组比较,其余4组细胞凋亡、脑水肿、神经细胞凋亡和炎症反应明显增高（P＜0.05）;与TBI组比较,TBI+ω-3组大鼠创伤后脑水含量降低,尤其在脑损伤3 d后降低更为明显［(78.14±0.57)%比（82.31±0.81）%,P＜0.01］,神经功能评分相应的改善明显（P＜0.05）。ω-3多不饱和脂肪酸抑制神经细胞凋亡和小胶质细胞的活化;降低大鼠TBI后升高的炎症因子TNF-α、IL-1α、IL-1β、IL-6 mRNA及蛋白表达水平;同时抑制了炎症因子上游JNK信号通路的活化。结论　ω-3多不饱和脂肪酸明显减轻大鼠TBI后脑水肿的程度,抑制神经细胞凋亡,改善伤后神经行为,其机制可能是通过抑制JNK信号通路和小胶质细胞的活化,减轻小胶质细胞介导的中枢性炎症反应,降低TNF-α、IL-1α、IL-1β、IL-6的表达。     

创伤性脑损伤后肠黏膜结构和屏障功能的变化

目的:探讨创伤性脑损伤后肠黏膜形态和屏障功能的变化,了解肠黏膜屏障功能障碍的发生时间及其严重程度. 方法:雄性Wistar 大鼠随机分为无脑损伤的对照组和脑损伤后3、12、24、72 h和7天组,每组6只.应用组织病理和电镜观察肠黏膜结构的变化,通过测定血浆内毒素水平和肠黏膜通透性,以评价肠黏膜屏障功能. 结果:创伤性脑损伤后3 h即出现肠黏膜的病理改变,然后逐渐加重.与对照组相比,脑损伤后3、12和24 h血浆内毒素水平明显升高,伤后72 h达到高峰,第7天开始下降.血浆内毒素水平在伤后3 h和72 h出现两个峰值.脑损伤后肠黏膜通透性明显增加. 结论:创伤性脑损伤后3 h即可引起明显的肠黏膜结构和屏障功能损害,至伤后72 h达高峰,此损害可持续7天以上.     

Neuroendocrine dysfunctions and their consequences following traumatic brain injury

Posttraumatic hypopituitarism is of major public health importance because it is more prevalent than previously thought. The prevalence of hypopituitarism in children with traumatic brain injury is unknown. Most cases of posttraumatic hypopituitarism remain undiagnosed and untreated in the clinical practice, and it may contribute to the severe morbidity seen in patients with traumatic brain injury. In the acute phase of brain injury, the diagnosis of adrenal insufficiency should not be missed. Determination of morning serum cortisol concentration is mandatory, because adrenal insufficiency can be life threatening. Morning serum cortisol lower than 200 nmol/L strongly suggests adrenal insufficiency. A complete hormonal investigation should be performed after one year of the trauma. Isolated growth hormone deficiency is the most common deficiency after traumatic brain injury. Sports-related chronic repetitive head trauma (because of boxing, kickboxing, football and ice hockey) may also result in hypopituitarism. Close co-operation between neurosurgeons, endocrinologists, rehabilitation physicians and representatives of other disciplines is important to provide better care for these patients.     

Amiloride increases neuronal damage after traumatic brain injury in rats

OBJECTIVE: It is well known that traumatic brain injury (TBI) decreases brain free magnesium (Mg) concentration, and that administration of Mg salts after TBI restores concentration of Mg in brain and improves functional outcome. In the presence of hemorrhage, administration of Mg salts exacerbates the injury process and worsens outcome. An alternative to administration of Mg salts may be to prevent cellular loss of Mg with use of amiloride, which inhibits the Na(+)/Mg(2+) exchange. METHODS: In the present study, male, adult Sprague-Dawley rats were injured using the impact acceleration model of diffuse TBI and administered either 100 mols/kg i.v. amiloride, or an equal volume of 50% DMSO/saline, 30 minutes (min) after injury. RESULTS: Amiloride did not improve functional outcome (motor or cognitive outcome) after TBI relative to vehicle treated controls. Histologically, treatment with amiloride significantly increased hippocampal caspase-3 expression (apoptosis), axonal swellings in the medulla and the degree of dark cell change (cell stress) in the cortex. Phosphorus NMR demonstrated that amiloride did not increase free Mg concentration after injury. CONCLUSIONS: Thus, amiloride is ineffective in preventing Mg loss after TBI when administered 30 min after trauma. Moreover, by administering amiloride after the TBI-related Mg decline has already been initiated, it may exacerbate injury by, in part by inhibiting Na(+)/Mg(2+) antiport and preventing entry of Mg back into the cell, and also by inhibiting other Na(+) linked transporters.     

Long-term employment outcomes in a rural area following traumatic brain injury

ABSTRACT: One of the major sequelae following traumatic brain injury is a change in employment status. This poses significant challenges for rehabilitation services. Several studies have investigated the longer-term outcome after traumatic brain injury. Longer-term outcome in an economically disadvantaged rural environment with limited rehabilitation services has not been studied extensively. A group of individuals (n = 65 ) who sustained a traumatic brain injury were compared regarding pre- and post-employment status. The moderate and severely injured sub-groups showed a significant change in employment status. Ideally rehabilitation programs should target re-employment as an outcome. Limited employment opportunities in rural areas may make this more difficult to achieve.     

颅脑损伤并发尿崩症的观察及护理

目的：探讨颅脑损伤并发尿崩症的护理，提高护理质量和治疗效果。方法：15例颅脑损伤并发尿崩症患者，24h尿量〉4000ml，尿比重〈1．006视为尿崩，观察血压、尿量、心率变化，监测血清钾、钠、血糖水平及尿、血渗透压水平。结果：13例治愈，1例因原发颅脑损伤严重死亡，1例因严重水、电解质平衡紊乱及多器官功能衰竭而死亡。治愈患者中，疗程最短9天，最长2个月，平均24天。结论：积极采取护理措施，准确了解病情，及时监测尿量、尿比重和血、尿电解质等，为早期诊断和治疗颅脑损伤后尿崩症，处理原发颅脑损伤提供依据，能明显改善颅脑损伤后尿崩症的预后。     

武汉市儿童脑外伤患者家庭负担的前瞻性研究

目的了解武汉市儿童脑外伤后家庭负担变化的基本状况.方法以0～17岁脑外伤患者作为研究对象进行前瞻性研究,分别于儿童住院期间及出院6个月后,利用以上经过检验的家庭负担测量工具,测量儿童家庭所承受的压力和负担及其变化,并利用儿童行为量表（CBCL）对脑外伤后儿童的社会行为能力进行评估.结果113例儿童在脑外伤发生前、住院期间及出院6个月后随访时家庭功能评价问卷（APGAR）平均得分分别为7.96、6.94、7.60分,配对t检验显示,家庭功能在外伤发生后发生障碍,6个月后恢复到外伤发生前的水平,但重度脑外伤对家庭功能的影响在出院6 个月后仍未得到恢复.住院期间疾病家庭负担会谈量表（FBS）得分最高的3个维度分别为家庭经济负担、家庭日常生活、家庭娱乐活动.出院6个月后FBS量表总得分下降,家庭成员心理健康维度得分最高,其次为家庭经济负担维度和家庭关系维度,配对t检验结果表明脑外伤对家庭成员心理健康的影响在儿童出院6个月后尚未得到消除.113例儿童出院6个月后CBCL得分均在正常范围内.结论脑外伤发生后家庭APGAR得分降低,FBS得分提高,表明脑外伤儿童的家庭受到伤害事件的影响,其家庭负担加重,家庭功能发生障碍.随着疾病的康复,除重度脑外伤组以外,脑外伤儿童的家庭功能均可恢复正常.     

膳食纤维对弥漫性脑损伤大鼠肠黏膜屏障的保护作用

目的:研究膳食纤维对重型颅脑损伤大鼠受损肠屏障功能的保护作用。方法:将大鼠致重型颅脑损伤后,随机分为A组(给予等渗盐水)和B组(给予膳食纤维),分别于伤后6、12、24、48和72 h处死大鼠。距回盲部5 cm处向上取2 cm小肠组织,在光镜下观察其病理形态变化。取门静脉血检测血浆微量内毒素的变化,取腹主动脉血测血浆二胺氧化酶、D-乳酸的变化。结果:①致伤后大鼠各组肠黏膜组织结构受损,内毒素、二胺氧化酶、D-乳酸值明显升高,以伤后12～24 h最显著,至72 h仍未恢复;②B组大鼠早期添加膳食纤维,至伤后48 h对上述各观察指标有明确改善。结论:重型颅脑损伤大鼠早期应用EN添加膳食纤维对肠屏障有保护作用。     

Gender differences in discharge destination among older adults following traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of death and disability, and the highest in-patient admission rates are among older adults. We identified that gender independently influences discharge destination following TBI in older adults. In this cross-sectional study, we examined discharge destinations of patients admitted to acute care over a 4-year period, as captured by the Ontario Trauma Registry (n = 3,480). Following TBI, women were significantly more likely than men to be sent to long term care facilities rather than home settings (p < .05), controlling for age, injury severity, mechanism of injury, and comorbidities.     

依达拉奉对脑创伤大鼠学习记忆功能影响

目的 探讨依达拉奉(edaravone)对脑创伤的保护作用.方法 112只雄性SD大鼠随机分为3组:对照组、创伤组、依达拉奉干预组.Marmarou's法建立弥漫性脑创伤模型.电镜观察海马区神经细胞形态变化;蛋白印迹(Western-Blot)法检测磷酸化细胞外信号调节激酶1/2(ERK1/2)表达;水迷宫法测试动物学习记忆功能.结果 与对照组比较,磷酸化ERK1/2在伤后1～48h表达水平明显增高(P<0.05);学习记忆指标潜伏期明显延长(P<0.05).依拉达奉干预组磷酸化ERK1/2表达水平在1,6,24与48h分别为(1.29±0.27),(3.48±1.49),(5.39±2.13)和(1.90±0.72),与创伤组比较明显下降(P<0.05);依拉达奉干预组学习记忆指标潜伏期分别为186.8,100.9,70.6,63.5和60.9s,明显短于创伤组(P<0.05).结论 依拉达奉可抑制脑创伤后ERK1/2活化,对脑创伤后学习记忆损害有改善作用.     

创伤性脑损伤后肠黏膜细胞凋亡和c-fos基因表达

目的:研究创伤性脑损伤(TBI)后小肠黏膜细胞凋亡及c-fos基因表达,探讨肠黏膜上皮细胞凋亡在破坏肠黏膜屏障中的作用及c-fos基因表达与凋亡的关系.方法:雄性Wistar大鼠,随机分为假手术(对照)组和脑创伤后3 h、12 h、24h、72 h和7 d组,采用自由落体撞击致重型颅脑损伤.在各时相点取空肠近端,应用TUNEL法观测小肠黏膜细胞凋亡,应用免疫组化法观察c-fos基因的表达.结果:①凋亡细胞以肠黏膜上皮细胞为主;②脑损伤后3 h肠黏膜上皮即出现明显凋亡,凋亡细胞的数量以伤后72 h最多,分布于绒毛顶端,后延伸至绒毛中下部;③脑损伤后肠黏膜上皮细胞的c-fos基因表达逐渐增强,主要出现在上皮细胞、平滑肌细胞和淋巴细胞,伤后24h、72h和7d的表达明显升高.结论:创伤性脑损伤可引起大鼠小肠黏膜细胞明显凋亡和c-fos基因的显著表达.     

谷氨酰胺对创伤性脑损伤后肠黏膜屏障的影响

目的探讨谷氨酰胺对大鼠创伤性脑损伤后肠黏膜屏障的影响。方法54只雄性Wistar成年大鼠分为对照组（N组，6只）、脑损伤组（T组，24只）及脑损伤后谷氨酰胺治疗组（G组，24只），T和G组按脑损伤后检测时间分为1、3、5．7d组，6只／组，应用组织病理和电镜观察肠黏膜结构的变化，并测定血浆内毒素水平，来评价肠黏膜屏障功能。结果谷氨酰胺能减轻创伤性脑损伤后肠黏膜的病理损害，使血浆内毒素水平降低。结论谷氨酰胺对创伤性脑损伤后肠黏膜屏障损害有一定的保护作用。     

创伤性脑损伤后小鼠肠道Toll样受体4的表达

目的:探讨Toll样受体4(TLR4)在创伤性脑损伤后肠道的表达变化。方法:将小鼠随机分为对照组和脑损伤后4 h、24 h和7 d组,每组5只。观察小鼠脑损伤后肠黏膜组织的改变,用免疫组化技术观察TLR4蛋白表达,实时RNA检测肠道TLR4mRNA表达。结果:小鼠创伤后4 h肠黏膜出现病理改变,并逐渐加重。TLR4蛋白阳性细胞伤后4 h升高,24 h达到高峰,7 d下降。TLR4mRNA水平伤后4 h升高,24 h达到高峰,7 d下降。结论:小鼠创伤性脑损伤后,可引起肠道TLR4表达增高。     

创伤性脑损伤后大鼠脑神经元凋亡和脑死亡相关蛋白激酶的表达变化

目的探讨大鼠创伤性脑损伤后死亡相关蛋白激酶（DAPK）的表达变化,寻找药物治疗的时间窗。方法选择自由落体法建立脑损伤模型,60只Wister大鼠随机分为正常对照组、假手术组和损伤组,损伤组于损伤后分别于2、8、24、48和72h取脑组织。HE染色观察组织病理变化;RT—PCR法检测DAPKmRNA的表达;TUNEL法检测神经细胞凋亡。结果脑损伤8h后DAPKmRNA的表达开始增高并出现明显的神经元凋亡;伤后24hDAPK的表达神经元凋亡二者都达到高峰,随后二者逐渐降低。结论创伤性脑损伤诱导DAPK表达和神经元凋亡,二者在伤后24h达到高峰,药物治疗时间窗为伤后24h。