大鼠神经干细胞经枕大池移植对脑损伤的影响

目的探讨神经干细胞(NSCs)经枕大池移植到创伤性脑损伤模型大鼠蛛网膜下腔中,观察其向损伤脑组织迁移及治疗效果。方法体外培养的NSCs取自子鼠皮层,并用5-溴脱氧尿嘧啶(BrdU)标记。采用Feeney’s自由落体脑创伤模型制成大鼠脑损伤模型,伤后24 h将NSCs经枕大池移植到蛛网膜下腔,伤前24 h、伤后24 h及1、2周行动物运动神经功能评分,分别于第1、2周处死取脑,行免疫组织化学染色检测BrdU、微管相关蛋白2(MAP2)、胶质纤维酸性蛋白(GFAP)。结果免疫组织化学染色表明,有BrdU( )NSCs迁移到脑内损伤灶并分化成MAP2 ( )神经元或GFAP( )胶质细胞。接受NSCs移植组大鼠与损伤组大鼠比较运动功能明显改善。结论NSCs具有从蛛网膜下腔迁移入脑内损伤组织、分化为神经元及神经胶质细胞并促进或改善神经功能恢复的能力。     

Attenuation of working memory and spatial acquisition deficits after a delayed and chronic bromocriptine treatment regimen in rats subjected to traumatic brain injury by controlled cortical impact

Cognitive impairments are pervasive and persistent sequelae of human traumatic brain injury (TBI). In vivo models of TBI, such as the controlled cortical impact (CCI) and fluid percussion (FP), are utilized extensively to produce deficits reminiscent of those seen clinically with the hope that empirical study will lead to viable therapeutic interventions. Both CCI and FP produce spatial learning acquisition deficits, but only the latter has been reported to impair working memory in rats tested in the Morris water maze (MWM). We hypothesized that a CCI injury would impair working memory similarly to that produced by FP, and that delayed and chronic treatment with the D2 receptor agonist bromocriptine would attenuate both working memory and spatial learning acquisition deficits. To test these hypotheses, isoflurane-anesthetized adult male rats received either a CCI (2.7 mm deformation, 4 m/sec) or sham injury, and 24 h later were administered bromocriptine (5 mg/kg, i.p.) or vehicle, with continued daily injections until all behavioral assessments were completed. Motor function was assessed on beam balance and beam walking tasks on postoperative days 1-5 and cognitive function was evaluated in the MWM on days 11-15 for working memory (experiment 1) and on days 14-18 for spatial learning acquisition (experiment 2). Histological examination (hippocampal CA1 and CA3 cell loss/survival and cortical lesion volume) was conducted 4 weeks after surgery. All injured groups exhibited initial impairments in motor function, working memory, and spatial learning acquisition. Bromocriptine did not affect motor function, but did ameliorate working memory and significantly attenuated spatial acquisition deficits relative to the injured vehicle-treated controls. Additionally, the injured bromocriptine-treated group exhibited significantly more morphologically intact CA3 neurons than the injured vehicle-treated group (55.60 +/- 3.10% vs. 38.34 +/- 7.78% [p = 0.03]). No significant differences were observed among TBI groups in CA1 cell survival (bromocriptine, 40.26 +/- 4.74% vs. vehicle, 29.13 +/- 6.63% [p = 0.14]) or cortical lesion volume (bromocriptine, 17.78 +/- 0.62 mm3 vs. vehicle, 19.01 +/- 1.49 mm3 [p > 0.05]). These data reveal that CCI produces working memory deficits in rats that are similar to those observed following FP, and that the delayed and chronic bromocriptine treatment regimen conferred cognitive and neural protection after TBI.     

Thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury

Objective: To investigate the clinical characteristics and significance of thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury (TBI). Methods:Ninety-six inpatients with severe brain injury were randomized into three groups: SBC (selective brain cooling) group (n=24), MSH (mild systemic hypothermia ) group (n=30), and control (normothermia) group (n=42). The platelet counts and prognosis were retrospectively analyzed. Results: Thrombocytopenia was present in 18 (75%), 23 (77%) and 15 (36%) patients in SBC group, MSH group and control group, respectively (P<0. 01). Thrombocytopenia, in which the minimum platelet count was seen 3 days after hypothermia, showed no significant difference between SBC and MSH group (P>0.05). Most platelet counts (37 cases, 90 %) in hypothermia group were returned to normal level after 1 to 2 days of natural rewarming. The platelet count in SBC group reduced by 16%, 27% and 29% at day 1, 3 and 5 respectively compared with the baseline value. Good recovery ( GOS score 4-5) rate of thrombocytopenia 1 year after injury for hypothermia group (17 cases, 37%) was significantly lower than that of control group (P < 0.01). Conclusions: Therapeutic hypothermia increases the incidence of thrombocytopenia in severe TBI, and patients with thrombocytopenia after therapeutic hypothermia are associated with unfavorable neurological prognosis.     

Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells

OBJECTIVE: To study the effect of bone marrow stromal cells administered intravenously to female rats subjected to traumatic brain injury. METHODS: We injected marrow stromal cells harvested from male rat bone marrow (n = 24) into the tail vein of the female rat (n = 8) 24 hours after traumatic brain injury; the rats were killed at Day 7 or 14 after treatment. The neurological function of the rats was evaluated using the rotarod test and the neurological severity score. The distribution of the male donor cells in brain, heart, lung, kidney, liver, muscle, spleen, and bone marrow of the female recipient rats was measured by identifying Y chromosome-positive cells using fluorescent in situ hybridization. RESULTS: We found that marrow stromal cells injected intravenously significantly reduced motor and neurological deficits compared with control groups by Day 15 after traumatic brain injury (P < 0.05, analysis of covariance for repeated measures). The transplanted cells preferentially engrafted into the parenchyma of the injured brain and expressed the neuronal marker NeuN and the astrocytic marker glial fibrillary acidic protein. Marrow stromal cells were also found in other organs in female rats subjected to traumatic brain injury without any obvious adverse effects. CONCLUSION: These data suggest that the intravenous administration of marrow stromal cells may be a promising therapeutic strategy that warrants further investigation for patients with traumatic brain injury.     

Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia

Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head-injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 +/- 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p less than 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF less than or equal to 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful.     

Sequential pharmacotherapy with magnesium chloride and basic fibroblast growth factor after fluid percussion brain injury results in less neuromotor efficacy than that achieved with magnesium alone

Combinational pharmacotherapy with individually efficacious agents is a potential strategy for the treatment of traumatic central nervous system (CNS) injury. Basic fibroblast growth factor (bFGF) has been shown to be neuroprotective against excitotoxic, ischemic, and traumatic injury to the CNS, while acute posttraumatic treatment with magnesium (Mg2+) has been shown to decrease the motor and cognitive deficits following experimental brain injury. In this study, bFGF and Mg2+ were evaluated separately and in combination to assess their potential additive effects on posttraumatic neurological recovery and histological cell loss (lesion volume). Twenty minutes after fluid percussion (FP) brain injury of moderate severity (2.2-2.4 atm), anesthetized rats received a 15-min intravenous infusion of either 125 mumol of MgCl2 or vehicle, followed 5 min later by a 24-h constant intravenous infusion of either bFGF (16 micrograms/h) or vehicle. Injured animals had a significant motor deficit when compared to sham (uninjured) animals at both 48 h and 7 days postinjury. At 48 h postinjury, there were no significant differences among injured animals when compared by treatment. By 7 days postinjury, injured animals treated with MgCl2 alone displayed significantly improved motor function when compared to brain-injured, vehicle-treated animals (p < 0.05). Animals treated with either bFGF alone or a combination of MgCl2 and bFGF displayed no significant neurological improvement relative to vehicle-treated injured animals at 7 days. No effect of any drug treatment of combination was observed on the extent of the postinjury lesion volume in the injured cortex. These results suggest that caution must be exercised when combining "cocktails" of potentially neuroprotective compounds in the setting of traumatic brain injury.     

Improved motor outcome in response to magnesium therapy received up to 24 hours after traumatic diffuse axonal brain injury in rats

OBJECT: The goal of this study was to establish the therapeutic window during which delayed therapy with MgSO4 improves neurological motor outcome in rats that have suffered severe traumatic axonal brain injury. METHODS: Severe brain injury was induced in male Sprague-Dawley rats by using the impact-acceleration model of severe traumatic diffuse axonal brain injury. Injured animals were subsequently treated with MgSO4 (750 micromol/kg) infused intramuscularly at 30 minutes or at 8, 12, or 24 hours after trauma and were tested for neurological motor outcome during the following week by using the rotarod test. Injured untreated (control) animals demonstrated highly significant (p < 0.001) neurological motor deficits that were sustained over the 1-week assessment period. Animals treated with MgSO4 at 30 minutes or at 8 or 12 hours postinjury demonstrated significantly improved motor outcomes compared with untreated control animals at all time points (0.001 < p < 0.05). Animals treated with MgSO4 at 24 hours had motor scores that were similar to those of untreated control animals early in the week, but demonstrated a significantly more rapid recovery in function and, by the end of the assessment period, they demonstrated significantly improved motor scores (p < 0.01). Repeated administration of MgSO4 over the 1-week observation period did not further improve outcome. CONCLUSIONS: The present results demonstrate that Mg++ plays a neuroprotective role following severe diffuse traumatic axonal brain injury. Moreover, Mg++ therapy significantly improved motor outcome when administered up to 24 hours after injury, with early treatments providing the most significant benefit. Repeated administration beyond 24 hours postinjury did not provide additional neuroprotection.     

Neural and marrow-derived stromal cell sphere transplantation in a rat model of traumatic brain injury

OBJECT: This study was designed to investigate the effect of treatment with a novel composite material consisting of embryonic neurospheres and bone marrow-derived stromal cell spheres (NMSCSs) in a rat model of traumatic brain injury (TBI). METHODS: The NMSCS composite was injected into the TBI contusion site 24 hours after injury, and all rats were killed on Day 14 after the transplantation. The Rotarod test and the neurological severity score were used to evaluate neurological function. The transplanted NMSCS was analyzed in recipient rat brains by using histological staining and laser scanning confocal microscopy. The lesion volumes in the brains were also calculated using computer image analysis. CONCLUSIONS: Rats that received NMSCS transplants had reduced lesion volume and showed improved motor and neurological function when compared with control groups 14 days after the treatment. These results suggest that transplantation of this novel biological material (NMSCS) may be useful in the treatment of TBI.     

Determinants of hospital costs associated with traumatic brain injury in England and Wales

Using data from the Trauma Audit Research Network, we investigated the costs of acute care in patients > or = 18 years of age hospitalised for traumatic brain injury between January 2000 and December 2005 in England and Wales. Traumatic brain injury patients were defined and stratified using the Abbreviated Injury Scale. A total of 6484 traumatic brain injury patients were identified; 22.3% had an Abbreviated Injury Scale score of three, 38.0% of four and 39.7% of five. Median age (IQR) was 42 years (28-59) and 76.7% were men. Primary cause of injury was motor vehicle collisions (42.4%) followed by falls (38.0%). In total 23.7% of the patients died before discharge. Hospitalisation costs averaged 15,462 pounds sterling (SD 16,844 pounds sterling). Costs varied significantly by age, Glasgow Coma Score, Injury Severity Score, coexisting injuries of the thorax, spine and lower limb, hospital mortality, availability of neurosurgical services, and specialty of attendants seen in the Accident and Emergency department.     

Traumatic atlantooccipital dislocation with survival: case report and review of the literature

Summary We present the case of a patient with traumatic atlantooccipital dislocation. The initial neurological examination showed no abnormalities. Dislocation was the result of rapid deceleration in a motor vehicle accident. The mechanism of injury was hyperextension/rotation, probably combined with a distraction force. Only a few cases of atlantooccipital dislocation without neurological involvement have been reported. Every report pointed out difficulties of initial diagnosis. Special attention should be directed toward the atlanto-odontoid-basion relationships as seen on lateral radiographs. Prompt recognition and surgical stabilization are essential to avoid further neurological injury.     

单唾液酸四己糖神经节苷脂钠注射液治疗重型颅脑损伤的疗效观察

目的观察单唾液酸四己糖神经节苷脂钠注射液对重型颅脑损伤患者血浆肌酸激酶同工酶BB（CreatinekinaseBB,CK-BB）的动态变化以及临床疗效。方法将60例重型颅脑损伤患者（GCS≤8分）分成两组,观察组30例在常规治疗的基础上加用单唾液酸四己糖神经节苷脂钠注射液治疗,对照组30例采用常规治疗。观察患者血浆CK-BB变化,并两组于伤后6个月按GOS预后评分评定预后,同时比较两组患者的意识好转率。结果观察组患者血浆CK-BB明显低于对照组。观察组恢复良好率（17/30）与对照组（8/30）比较,差异有统计学意义（P〈0.05）。观察组治疗后1个月清醒23例,而对照组l3例,两组清醒率比较,差异有统计学意义（P〈0.01）。两组清醒时间比较,观察组为（14.56±6.56）天,对照组为（20.85±10.92）天。结论单唾液酸四己糖神经节苷脂钠注射液能有效降低重型颅脑损伤患者血浆CK-BB的水平,并且不仅能加速重型颅脑损伤患者清醒,还能促进预后,提高生活质量。单唾液酸四己糖神经节苷脂钠注射液是治疗重型颅脑损伤安全有效的药物,可以广泛地应用于临床。     

Traumatic intracerebral hematoma--which patients should undergo surgical evacuation? CT scan features and ICP monitoring as a basis for decision making

When a patient presents to the neurosurgeon with a traumatic intracerebral hematoma and has not deteriorated or developed new neurological deficit since the injury, the decision to remove the hematoma may be difficult. Of 244 patients with traumatic intracerebral hematomas, 85 were selected for intracranial pressure monitoring to assist in deciding whether surgical evacuation was indicated. None had deteriorated in conscious level or developed new neurological deficit since injury. Fifty-five patients (65%) demonstrated high intracranial pressure and underwent craniotomy. In 30 patients, intracranial pressure remained under 30 mm Hg, and their hematomas were not initially removed. Five of these 30 patients suddenly deteriorated or died 6 to 11 days after injury, with features of high intracranial pressure clinically or at postmortem. Intracranial pressure monitoring therefore failed to predict a late rise in intracranial pressure in 16.6% of those with low intracranial pressure initially. An analysis of computed tomography scanning and clinical features was therefore carried out to search for better predictors of the need for surgery. Our data suggest that basal cistern status, coma score, and the severity of edema surrounding the intracerebral hematoma should be used, in addition to intracranial pressure monitoring, to improve management of patients with traumatic intracerebral hematoma.     

Neurosurgical trauma in People's Republic of China

An epidemiological investigation for neurological disorders was conducted in the People's Republic of China in 1983 and 1985. The incidence of traumatic neurological injury was 55.4 patients per 100,000 population in the six big cities and 64.1 patients in the 21 rural areas. The mortality rates were 6.3 per 100,000 population (male:female = 1.7:1.0) in the six cities and 9.7 (m:f = 2.5:1) in the rural areas. In the cities, the causes of brain injury were vehicle accidents (31.7%), followed by assaults (23.8%), falls (21.8%), stumbles (15.4%), and others. Brain concussion was 68.4%, contusion was 26.0%, and intracranial hematoma was 5.6%. The incidence of spinal cord injury was 0.67 per 100,000 population in Beijing and 1.37 in Shanghai. Male versus female ratio was 7 to 1 and the peak incidence was found in ages from 20 to 30 years old. In the past decade, vehicle accidents increased along with the increasing number of cars and motor bicycles. As a result of a series of administrative measures, such as improvement of traffic control and safe-driving education, mean mortality decreased from 33.4 per 10,000 motor vehicles in 1990 to 22.0 in 1995. It has been estimated that approximately 50,000 to 60,000 people die from vehicle accidents per year. Among these cases, brain injury accounts for 39% to 57% and spinal cord injury about 10%. Since vehicle accidents are the most common cause for neurotraumatic death, an effort is needed to prevent and to decrease the incidence of these accidental traumatic injuries.     

Bilateral hemicraniectomy in non-penetrating traumatic brain injury

Traumatic brain injury is a heterogeneous entity that encompasses both surgical and non-surgical conditions. Surgery may be indicated with traumatic lesions such as hemorrhage, fractures, or malignant cerebral edema. However, the neurological exam may be clouded by the effects of medications administered in the field, systemic injuries, and inaccuracies in hyperacute prognostication. Typically, neurological injury is considered irreversible if diffuse loss of grey/white matter differentiation or if brainstem hemorrhage (Duret hemorrhage) exists. We aim to characterize a cohort of patients undergoing bilateral hemicraniectomy for severe traumatic brain injury. A retrospective consecutive cohort of adult patients undergoing craniectomy for trauma was established between the dates of January 2008 and November 2011. The primary outcome of the study was in-hospital mortality. Secondary outcomes were ICU length of stay, surgical complications, and Glasgow Outcome Score at most recent follow-up. During the study period, 210 patients undergoing craniectomy for traumatic mass-occupying lesion (epidural hematoma, subdural hematoma, or parenchymal contusion) were analyzed. Of those, 9 met study criteria. In-hospital mortality was 67% (6 of 9 patients). The average ICU length of stay was 12 days. The GOS score was 3 in surviving patients. Bilateral hemicraniectomy is a heroic intervention for patients with severe TBI, but can be a life-saving procedure.     

等热量不同糖成分营养制剂对重型颅脑损伤患者血糖影响的随机对照研究

目的探讨持续泵人等热量不同糖成分营养制剂对重型颅脑损伤患者血糖的影响。方法60例重型颅脑损伤患者随机分为普通肠内营养制剂组（30例）和糖尿病专用型肠内营养制剂组（30例）,在相等非蛋白热量（104．6kJ／Kg·d）摄入条件下,进行14天不同糖成分的肠内营养制剂对重型颅脑损伤患者血糖影响的前瞻性随机对照研究。结果两组患者2周内每日平均血糖水平及每日平均胰岛素剂量比较差异无显著性（P〉0．05）。28天生存率和改良Rankin评分两组比较差异均无显著性（P〉0．05）。结论持续肠内泵入普通肠内营养制剂和糖尿病专用型肠内营养制剂对血糖影响差异不明显,重型颅脑损伤并发高血糖患者可选择该制剂。     

Bromocriptine in traumatic brain injury

The authors report the case of a 63-year-old patient with severe traumatic brain injury (TBI) associated with Parkinson's syndrome, whose performances were dramatically improved by bromocriptine therapy, with an improvement of the scores, not only on tests evaluating motor functions but also on tests evaluating the patient's cognitive functions. However, no improvement was observed with levodopa.     

Mild head injury increasing the brain's vulnerability to a second concussive impact.

OBJECT: Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI. METHODS: Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury. observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta-amyloid or tau were observed in any brain-injured animal. CONCLUSIONS: On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.     

low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits

Low-level laser therapy (LLLT) has been evaluated in this study as a potential therapy for traumatic brain injury (TBI). LLLT has been found to modulate various biological processes. Following TBI in mice, we assessed the hypothesis that LLLT might have a beneficial effect on their neurobehavioral and histological outcome. TBI was induced by a weight-drop device, and motor function was assessed 1 h post-trauma using a neurological severity score (NSS). Mice were then divided into three groups of eight mice each: one control group that received a sham LLLT procedure and was not irradiated; and two groups that received LLLT at two different doses (10 and 20 mW/cm(2) ) transcranially. An 808-nm Ga-As diode laser was employed transcranially 4 h post-trauma to illuminate the entire cortex of the brain. Motor function was assessed up to 4 weeks, and lesion volume was measured. There were no significant changes in NSS at 24 and 48 h between the laser-treated and non-treated mice. Yet, from 5 days and up to 28 days, the NSS of the laser-treated mice were significantly lower (p < 0.05) than the traumatized control mice that were not treated with the laser. The lesion volume of the laser treated mice was significantly lower (1.4%) than the non-treated group (12.1%). Our data suggest that a non-invasive transcranial application of LLLT given 4 h following TBI provides a significant long-term functional neurological benefit. Further confirmatory trials are warranted.     

脑外伤后进展性出血性损伤的发生率及其危险因素分析

目的调查脑外伤后进展性出血性损伤的发生率,分析其发生的危险因素。方法回顾性分析2009年6月至2011年6月本院收治的168例脑外伤患者。收集年龄、性别、入院时间、入院时GCS评分、蛛网膜下腔出血、中线移位、环池形态、瞳孔散大、急诊手术、首次CT时间、创伤严重程度评分和APACHEⅡ评分等资料。计算脑外伤后进展性出血性损伤的发生率,采用非条件多因素Logistic回归分析确定脑外伤后进展性出血性损伤发生的危险因素。结果 63例(37.5%)脑外伤患者发生进展性出血性损伤。多因素Logistic回归分析显示,蛛网膜下腔出血(OR=12.421,95%CI=1.263～42.715,P=0.001)和首次CT时间(OR=0.421,95%CI=0.263～0.715,P=0.002)是脑外伤后进展性出血性损伤发生的独立危险因素。结论脑外伤后进展性出血性损伤发生率较高,外伤性蛛网膜下腔出血和短时间内完成首次CT检查是脑外伤后进展性出血性损伤的独立危险因素。