大鼠创伤性脑损伤后认知行为的变化

目的 建立直接手术损伤大鼠部分脑皮质及海马CA1区的创伤性脑损伤模型,并观察损伤后动物认知行为的改变情况.方法 将大鼠进行脑损伤建模后,于术后11～15 d和26～30 d采用Morris水迷宫的方法评价动物的认知行为变化后,灌杀动物取脑切片,HE染色及尼氏染色观察损伤范围;胶质纤维酸性蛋白(GFAP)免疫组织化学染色观察星型胶质细胞(AST)的活化及胶质瘢痕形成情况;术后5 d行Nestin及GFAP双重免疫荧光染色显示海马内干细胞的激活,并观察损伤边缘的干细胞迁移情况.结果 直接手术损伤部分脑皮质及海马CA1区后,造成了动物认知功能障碍,并且1个月时有自发的认知功能恢复;5 d时星型胶质细胞活化,1个月时胶质瘢痕的形成.结论 本实验采用的模型可成功造成动物认知行为的改变,为组织工程材料的移植治疗脑损伤提供了比较适用的研究模型.     

Hypopituitarism after traumatic brain injury

Traumatic brain injury (TBI) is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. Post-traumatic hypopituitarism (PTHP) was recognized more than 80 years ago, but it was thought to be a rare occurrence. Recently, clinical evidence has demonstrated that TBI may frequently cause hypothalamic-pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. Changes in pituitary hormone secretion may be observed during the acute phase post-TBI, representing part of the acute adaptive response to the injury. Moreover, diminished pituitary hormone secretion, caused by damage to the pituitary and/or hypothalamus, may occur at any time after TBI. PTHP is observed in about 40% of patients with a history of TBI, presenting as an isolated deficiency in most cases, and more rarely as complete pituitary failure. The most common alterations appear to be gonadotropin and somatotropin deficiency, followed by corticotropin and thyrotropin deficiency. Hyper- or hypoprolactinemia may also be present. Diabetes insipidus may be frequent in the early, acute phase post-TBI, but it is rarely permanent. Severity of TBI seems to be an important risk factor for developing PTHP; however, PTHP can also manifest after mild TBI. Accurate evaluation and long-term follow-up of all TBI patients are necessary in order to detect the occurrence of PTHP, regardless of clinical evidence for pituitary dysfunction. In order to improve outcome and quality of life of TBI patients, an adequate replacement therapy is of paramount importance.     

Hormonal diseases after traumatic brain injury

Traumatic brain injury represents major medical and social problem in all developed countries. Its incidence is about 200 per 100,000 inhabitants per year. In the acute phase immediately after injury the posterior pituitary dysfunction is well-known. The incidence of severe grossly hypernatremic cases of diabetes insipidus (DI) is about 3%, less severe form of ADH insufficiency was recognized in 21-26%. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was described in about 14%. These changes are transient in most cases, persisting DI has an incidence of 5-7% and SIADH cases recover almost always. Since the beginning of this century several series evaluating prospectively all patients after moderate to severe TBI have been published. Permanent hypopituitarism was found in one quarter to one half of them. The most common turned out to be the growth hormone (17.6%) and gonadotropic (13.4%) deficiency. Less common is the corticotropic (8.4%) and thyrotropic (4.3%) insufficiency. In the majority of patients an isolated dysfunction was discovered. However, in 9%, a combined failure of two or more HPA axis was present. This paper describes the minimum investigation needed to diagnose hypopituitarism by patients after TBI, who may profit from substitution therapy.     

Recurrent hyponatremia after traumatic brain injury

Dysregulation of the neuroendocrine system is a frequent complication after traumatic brain injury (TBI). Symptoms of these hormonal abnormalities might be subtle and thus easily ignored. Hyponatremia usually indicates underlying disorders that disrupt fluid homeostasis. In most patients with TBI, hyponatremia is a feature of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion due to pituitary dysfunction after head injury. Usually TBI-associated hyponatremia is transient and reversible. We report the case of a 48-year-old man with TBI-associated hyponatremia with delayed recovery and recurrent hyponatremia precipitated by subsequent surgery. In this report, we emphasize the importance of identifying patients with slow recovery of the injured brain, which could complicate with SIADH and acute hyponatremia. Differentiating TBI-associated SIADH from other important causes of hyponatremia such as cerebral salt wasting, and hypocortisonism are also reviewed. Prevention of its recurrence by avoiding further risk is mandatory in managing patients with TBI.     

脑外伤与心电图异常关系的分析

目的:分析脑外伤患者脑伤情况与心电图异常率之间的关系.方法:选择同一时间段内住院治疗的161例脑外伤患者,比较、分析不同损伤程度、部位的脑伤患者心电图异常率,以及随着治疗心电图异常的恢复情况.结果:共出现心电图异常83例(51.55%),以各种心律失常、T波及ST段改变、左室高电压等最为常见.Glasgow评分越低、脑...     

重型颅脑损伤后颅内压变化对心电图的影响

目的 探讨重型颅脑损伤后不同颅内压水平对心电图的影响.方法 2010年3月至2014年3月122例重型颅脑损伤患者根据不同颅内压水平分为3组：颅内压维持20～30mmHg、颅内压维持在30～40mmHg、颅内压＞40mmHg,所有患者伤后24小时内经标准12导联心电图检查,应用SPSS 13.0统计学软件分析相关结果.结果 122例重型颅脑损伤患者心电图异常81例,占66.4％,3组之间异常心电图差异主要反映在异常Q波、QT间期延长、ST-T变化、窦性心动过缓及过速（p＜0.05）,并与颅内压水平成正相关,而在心律失常及传导阻滞方面的差异无统计学意义（p＞0.05）.结论 颅脑损伤后出现的异常心电图可作为初步评估损伤程度的参考指标,对患者病情的判断以及为医师提供诊疗参考具有一定的临床意义.     

Posterior pituitary dysfunction after traumatic brain injury

Disorders of water balance are well recognized after traumatic brain injury (TBI), but there are no reliable data on their true prevalence in post-TBI patients. We aimed to evaluate the prevalence of posterior pituitary dysfunction in a large cohort of survivors of TBI. One hundred two consecutive patients (85 males) who suffered severe or moderate TBI were evaluated for diabetes insipidus (DI) at a median of 17 months (range 6-36 months) after the event, using the 8-h water deprivation test (WDT). Their results were compared against normative data obtained from 27 matched, healthy controls. Patients' medical records were retrospectively reviewed for the presence of abnormalities of salt and water balance in the immediate post-TBI period. Twenty-two patients (21.6%) developed DI in the immediate post-TBI period (acute DI group), of whom five had abnormal WDT on later testing. In total, seven patients (6.9%) had abnormal WDT (permanent DI group), five of whom had partial DI. Patients in the acute and permanent DI groups were more likely to have more severe TBI, compared with the rest of the cohort (P < 0.05). In the immediate post-TBI period, 13 patients (12.9%) had syndrome of inappropriate secretion of antidiuretic hormone, which persisted in one patient, and one other patient developed cerebral salt wasting. Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone were common in the immediate post-TBI period. Permanent DI was present in 6.9% of patients who survived severe or moderate TBI, which is higher than traditionally thought. Identification of patients with partial posttraumatic DI is important because appropriate treatment may reduce morbidity and optimize the potential for recovery.     

Developmental traumatic brain injury decreased brain derived neurotrophic factor expression late after injury

Pediatric traumatic brain injury (TBI) is a major cause of acquired cognitive dysfunction in children. Hippocampal Brain Derived Neurotrophic Factor (BDNF) is important for normal cognition. Little is known about the effects of TBI on BDNF levels in the developing hippocampus. We used controlled cortical impact (CCI) in the 17 day old rat pup to test the hypothesis that CCI would first increase rat hippocampal BDNF mRNA/protein levels relative to SHAM and Na?ve rats by post injury day (PID) 2 and then decrease BDNF mRNA/protein by PID14. Relative to SHAM, CCI did not change BDNF mRNA/protein levels in the injured hippocampus in the first 2 days after injury but did decrease BDNF protein at PID14. Surprisingly, BDNF mRNA decreased at PID 1, 3, 7 and 14, and BDNF protein decreased at PID 2, in SHAM and CCI hippocampi relative to Na?ve. In conclusion, TBI decreased BDNF protein in the injured rat pup hippocampus 14 days after injury. BDNF mRNA levels decreased in both CCI and SHAM hippocampi relative to Na?ve, suggesting that certain aspects of the experimental paradigm (such as craniotomy, anesthesia, and/or maternal separation) may decrease the expression of BDNF in the developing hippocampus. While BDNF is important for normal cognition, no inferences can be made regarding the cognitive impact of any of these factors. Such findings, however, suggest that meticulous attention to the experimental paradigm, and possible inclusion of a Na?ve group, is warranted in studies of BDNF expression in the developing brain after TBI.     

大鼠创伤性脑损伤后肠黏膜屏障的应激性变化

目的探讨创伤性脑损伤后大鼠肠黏膜屏障的应激性变化及其发生的形态学基础。方法雄性Wistar大鼠64只,均分为创伤性脑损伤组和假手术对照组,再分别按术后6、12、24和48 h时相点分为4个亚组(n=8);偶氮显色法鲎实验定量测定门静脉血内毒素水平;荧光显微镜检测肠系膜淋巴结、肝、脾、胰、肺和肾组织匀浆中标记的大肠杆菌移位率;观察肠黏膜组织病理及扫描和透射电镜下超微结构的变化。数据采用t检验。结果损伤后6 h,脑损伤但大鼠内毒素水平即开始升高,为(0.382±0.014)Eu/ml,12 h为(0.466±0.018)Eu/ml,24 h达高峰,至(0.478±0.029)Eu/ml,此后回落, 48 h为(0.412±0.036)Eu/ml,仍未降至正常,与对照组各时相点内毒素水平(0.102±0.007、0.114±0.021、0.112±0.018、0.108±0.011)比较,差异有统计学意义(P值均<0.05);多脏器荧光标记检出大肠杆菌的大鼠数均比对照组明显升高(P<0.05);光学显微镜下脑损伤组大鼠肠黏膜上皮细胞受损;透射电镜下可见细胞间紧密连接较对照组增宽。结论大鼠创伤性脑损伤后早期肠黏膜屏障功能即受损,肠黏膜通透性增高,细胞间紧密连接增宽可能是其形态学基础。     

The history of pituitary dysfunction after traumatic brain injury

Pituitary - To estimate the total number of articles on traumatic brain injury (TBI)-related hypopituitarism and patients (including children and adolescents) with such disorder that were published...     

Predictors of anterior pituitary insufficiency after traumatic brain injury

Background Several studies have reported a high prevalence of hypopituitarism after traumatic brain injury (TBI). Risk stratification is a prerequisite for cost‐effective hormonal screening of these patients. However, it is still unclear which risk factors predispose patients to develop anterior hypopituitarism after TBI. Objective To assess clinical and radiological risk factors for post‐traumatic hypopituitarism. Patients and methods Seventy‐eight consecutive patients (52 men, 26 women; mean age 36·0 years, range 18–65 years) with mild, moderate or severe TBI were studied. Endocrine and clinical parameters were assessed 3 and 12 months after TBI. Results We found diffuse axonal injury, basal skull fracture and older age to be major risk factors of post‐traumatic hypopituitarism. Conclusions We have defined specific risk factors for the development of post‐traumatic hypopituitarism that are consistent with pathophysiological considerations. These findings might help to identify at‐risk patients.     

颅脑损伤患者下丘脑-垂体-性腺轴功能的变化及意义

目的观察急性颅脑损伤患者下丘脑—垂体—性腺轴功能的变化,探讨其临床意义。方法对75例急性颅脑损伤患者在伤后1 d采集静脉血,采用放射免疫法测定血清促黄体生成素（LH）、卵泡刺激素（FSH）、催乳素（PRL）、睾酮（T）、孕酮（P）及雌二醇（E2）水平。结果颅脑损伤后FSH、P水平下降,T、E2水平升高;与局限性脑损伤患者比较,弥漫性轴索伤患者FSH、P、T、及E2水平变化较大;颅脑损伤越严重,FSH、P、T及E2变化越大;与正常人及轻型损伤患者比较,重型损伤患者FSH、P、T及E2变化更大（P均〈0.05）。结论急性颅脑损伤可导致下丘脑—垂体—性腺轴功能改变,这一改变与损伤类型、损伤严重程度和性别等有关。     

Aerobic capacity and growth hormone deficiency after traumatic brain injury

CONTEXT: GH deficiency occurs in approximately 20% of all individuals who suffer from a moderate to severe traumatic brain injury. OBJECTIVE: This study determined whether GH deficiency secondary to traumatic brain injury had an effect on aerobic capacity. DESIGN: Subjects were screened for GH deficiency by the glucagon stimulation test and performed a maximal treadmill exercise test. SETTING: Patients were studied in the postacute recovery phase after traumatic brain injury. PARTICIPANTS: Thirty-five individuals were studied. Groups were formed as follows: normal GH axis, greater than 8 ng/ml response (n = 12); insufficient, GH 3-8 ng/ml response (n = 11); and deficient, less than 3 ng/ml response (n = 12). INTERVENTION: There was no intervention. MAIN OUTCOME MEASURE: Aerobic capacity was assessed by measuring expired gases during a graded treadmill exercise test. One-way and two-way ANOVAs were carried out on all peak and submaximal cardiorespiratory variables, respectively. Appropriate post hoc comparisons followed as necessary. RESULTS: Significantly higher peak oxygen consumption was found in traumatic brain injury subjects with GH normal vs. GH insufficient and deficient [26.4 +/- 6.9, 20.8 +/- 4.6, and 19.7 +/- 5.0, respectively (P < 0.05)]. Submaximal oxygen consumption was significantly higher in the GH normal group. All other variables were statistically similar. CONCLUSIONS: This study shows that individuals with traumatic brain injury with normal GH secretion have below normal aerobic capacity and those patients who have GH insufficiency/deficiency are further deconditioned. Studies of GH replacement in these subjects should be conducted to assess whether GH therapy can improve cardiorespiratory fitness and prevent secondary disability.     

Evaluation of pituitary function after traumatic brain injury in childhood

Objectives Post‐traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. Design Retrospective exploratory study. Patients: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4–21·7 years) and median (range) interval since injury 4·3 years (1·4–7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. Measurements Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records. Results No subject had short stature (mean height SD score +0·50, range −1·57 to +3·00). Suboptimal GH responses (<5 μg/l) occurred in six peri‐pubertal boys (one with slow growth on follow‐up) and one postpubertal adolescent (peak GH 3·2 μg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm . Nine of twenty‐five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH‐stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome. Conclusions No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.     

Endocrine changes in brain death and transplantation

Following brain death (BD) many hormonal changes occur. These include an increase and then a fall in the levels of circulating catecholamines, reduced levels of anti-diuretic hormone and cortisol as well as alterations in the hypothalamic-pituitary thyroid axis consistent with the non-thyroidal illness syndrome. In an era when the numbers of potential recipients listed for transplantation are greater than the number of donors, with an increasing donor age, a detailed knowledge of the endocrine changes and pathophysiological consequences of these is essential to optimise the management of the brain-stem dead organ donor. There still remains significant debate as to whether hormone replacement therapy to correct the observed changes is beneficial.     

Circadian blood pressure and heart rate changes in patients in a persistent vegetative state after traumatic brain injury

Alteration of autonomic nervous system regulation is known to be present in the persistent vegetative state after traumatic brain injury, termed the dysautonomic syndrome. This study assessed the circadian blood pressure and heart rate pattern and variability in the persistent vegetative state through noninvasive 24-hour ambulatory blood pressure monitoring. The study was performed in 20 subjects: 10 patients (six men and four women; mean age, 29.5+/-9.9 years; range, 19-39 years) in a vegetative state (mean, 27.3+/-5.6 days after trauma) and 10 healthy subjects as controls (six men and four women; mean age, 28+/-5.7 years; range, 29-37 years). The patients showed a blood pressure nondipper pattern; 24-hour, daytime, and nighttime values of blood pressure and heart rate were significantly higher in patients than in controls. The day-night difference in heart rate and blood pressure was also significantly lower in patients. Finally, SD and variation coefficients were significantly lower in patients. The results show changes in the variability and circadian blood pressure and heart rate patterns in persistent vegetative state patients with dysautonomic syndrome, as an expression of the sympathetic-parasympathetic activity imbalance in the control of vasomotor tone.