Changes in regional energy metabolism after cortical cold lesion in the rat brain

In the present investigation, regional ATP, glucose, and lactate contents were examined in the cortical and subcortical structures after cold lesion in rats. Bioluminescence imaging of ATP, glucose, and lactate was performed in serial tissue sections at 4 h (n=4), 12 h (n=4) and 24 h (n=4) after cold injury or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry, at the lesion site, in cortical areas, in the hippocampus, and in the thalamus. ATP and glucose content were significantly decreased at the lesion site as well as on the contralateral side after 4, 12, and 24 h postinjury. Lactate content increased significantly in the hippocampal area on the ipsilateral side at 12 h. Cortical lactate was bilaterally unchanged. The cold lesion injury led to a characteristic ischemic profile in the hippocampus signaled by low ATP and glucose content paralleled by high lactate levels. The otherwise global depletion of glucose and ATP suggests that other factors besides cerebral blood flow may contribute to the impairment of energy metabolism.     

Changes in cortical and subcortical energy metabolism after repetitive and single controlled cortical impact injury in the mouse

In the present investigation we examined regional ATP, glucose, and lactate content in the cortical and subcortical region, in a mouse model of controlled cortcal impact (CCI) injury. In serial tissue sections, bioluminescence imaging of ATP, glucose, and lactate was performed 1 h after a single CCI injury or sham surgery and 15 min, 1, 24, and 48 h after the induction of a second CCI injury 24 h later or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry at the lesion site, at the contralateral site, and in a subcortical region. After repetitive CCI injury, the cortical ATP content decreased bilaterally at 15 min and 1 h, and reached a significant minimum at 24 h, as compared with sham. At 48 h the ATP content bilaterally reached base level again. No significant changes in ATP were found in the subcortical region. After repetitive CCI injury, the lactate content increased bilaterally, reached a significant level at 15 min at the trauma site, and bilaterally reached a significant maximum at 1 h. Thereafter, lactate content decreased below base level without reaching significance and reached baseline again at 48 h. In the ipsilateral subcortical region, lactate content increased transiently above the baseline at 1 h and decreased to a significant minimum at 24 and 48 h. No significant changes were found in the contralateral subcortical area. No significant differences between glucose content in sham animals and the cortical and subcortical area could be measured over time; the subcortical glucose content was bilaterally lower than cortical content at all time points and reached a significant minimum bilaterally at 48 h after repetitive CCI injury compared with cortical glucose content. Single CCI injury did not affect ATP, glucose, and lactate contents at any time point. Repetitive CCI injury caused a more severe depression in cerebral metabolism at early time points after trauma compared with a single CCI injury and indicates that lactate might be an early indicator of post-traumatic metabolic disruption.     

Novel‐graded traumatic brain injury model in rats induced by closed head impacts

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Due to the heterogeneity of human TBI, none of the available animal models can reproduce the entire spectrum of TBI. This study was designed to develop a novel‐graded TBI rat model which is induced by closed head impacts (CHI) with reproducible brain damage and neurological dysfunction. A total of 75 male Sprague–Dawley rats (200 ± 20 g) were randomly equally divided into five groups: the Sham, 0.5, 0.6, 0.7 and 0.8 MPa groups. A custom‐made, air‐driven injury apparatus was used to induce CHIs (from 0.5 to 0.8 MPa). The kinematic parameters during the procedure were recorded by a force sensor and a high‐speed camera. Mortality rate, duration of unconsciousness (latency period of righting reflex), modified neurological severity score (mNSS) and whole brain water content (BWC) were examined. Pathological changes were evaluated by hematoxylin‐eosin (HE) stain and immunohistochemical stain for amyloid precursor protein (APP). The impact force and speed were 785.3 ± 14.12 N and 5.71 m/s in the 0.5 MPa group, 837.72 ± 10.41 N and 6.06 m/s in the 0.6 MPa group, 857.65 ± 11.11 N and 6.25 m/s in the 0.7 MPa group, and 955.6 ± 16.35 N and 6.67 m/s in the 0.8 MPa group. The periods of loss of righting reflex in 0.6–0.8 MPa groups were significantly higher than that in the Sham group. The mNSS score and BWC of the 0.8 MPa group remained higher 24 h after injury than other groups. Brain damage was indicated by increased APP expression in TBI rats. In conclusion, the newly developed CHI rat model was a highly controlled and reproducible graded TBI model, and provided a useful tool to investigate the underlying mechanism and therapeutic effects of TBI with various injury severities.     

Linguistic competence in paediatric closed head injury

The purpose of this investigation was to examine the effects of age at onset of traumatic brain injury on the linguistic competence of children and adolescents who sustained closed head injuries (CHI) that cause diffuse brain damage. The Test of Language Competence-Expanded Edition (TLC-E), a standardized test of subtle language abilities, was administered to 20 children who sustained severe CHI. The study determined whether 10 subjects who experienced CHI at a pre-adolescent age (4 to 11 years) and 10 subjects who experienced CHI at an adolescent age (13 to 18 years) showed quantitative differences in linguistic competence as measured by the TLC-E Test. The language abilities of children in both groups were compared to determine whether there were trends in performance relative to age of onset or type of subtest. In addition, experimental subjects' performance was compared to the normative population used to standardize the TLC-E. Hypotheses were constructed according to separate developmental and pathophysiological perspectives.     

大鼠头颅侧向旋转脑损伤模型脑干听觉诱发电位的变化

目的探讨头颅侧向旋转致脑损伤大鼠模型脑干听觉诱发电位（BAEP）的变化及机制。方法成年大鼠20只，制作头颅瞬间侧向旋转脑损伤模型，测量头颅旋转前及旋转后6h的BAEP，测量电极置于颅顶左侧c2点，左耳予短暂click声刺激，右耳持续予噪声掩蔽，经1000次叠加平均，记录BAEP各波形的潜伏期、波间期和波幅值。结果大鼠头颅旋转后6h和Ⅴ波潜伏期、Ⅰ～Ⅲ和Ⅲ～Ⅴ波波间期明显较旋转前延长，Ⅰ和Ⅴ波波幅较旋转前明显降低，而旋转前后Ⅰ波潜伏期、Ⅰ～Ⅴ波波间期以及Ⅰ波波幅无显著差异。结论头颅瞬间侧向旋转可引起BAEP异常，此与脑干内特殊传导通路的破坏有关，其结构基础为脑干广泛神经轴索损伤。     

Alcohol-dependent unilateral vestibular impairment persisting after a closed head injury

Summary A 20-year-old man suffered a closed head in-jury followed by symptoms of right-sided labyrinthine concussion with complete clinical recovery within 3 weeks. Episodic vertigo and ataxic gait occurred after the ingestion of small amounts of alcohol over the next 2 years. Electro-oculography revealed a right-sided peripheral type vestibular lesion, only after taking alcohol. This was interpreted as an alcohol-induced impairment of central compensation following an incomplete recovery from right-sided labyrinthine trauma.     

DNA fragmentation and nuclear endonuclease activity in rat brain after severe closed head injury

Previous studies have suggested that brain cells undergo apoptotic cell death during several neurodegenerative disorders such as Alzheimer's disease, Parkinsonism and ischemic stroke. In the present study, apoptotic DNA fragmentation and activation of nuclear endonuclease were evaluated in rat brain cells after head trauma. Severe closed head injury was induced in rats by the impact of a 450-g weight dropped from a height of 2 m. A 12% mortality was experienced after head trauma. Brain cell nuclei and DNA were isolated at intervals of 3, 10, 24 h, 3 and 10 days after head trauma. DNA fragmentation was measured by the random oligonucleotide-primed synthesis (ROPS) assay and was significantly increased with the maximum level of DNA fragmentation occurring at 10 h after trauma. The DNA and nuclei yields decreased 10 h after injury and remained at a reduced level at all subsequent sampling intervals. The DNA fragmentation induced after severe head trauma was accompanied by an increase in the activity of the Ca/Mg-dependent endonuclease associated with apoptosis. These data indicate that severe head injury is associated with significant brain cell death by apoptosis.     

大鼠急性脑损伤后脑局部代谢磁共振波谱分析

目的：本实验研究鼠急性颅脑损伤局部脑组织代谢的情况，以找出颅脑损伤与恢复过程中局部脑组织各种代谢成分变化的规律。方法：采用自由落体致鼠脑损伤模型，伤后３０分钟、３、２４、１６８小时取材，用核磁共振波谱法分析颅脑损伤局部脑组织代谢的变化。各组间采用ｔ检验。结果：颅脑损伤后伤区脑组织乳酸含量于伤后３小时已显著增高（Ｐ＜０．０１），伤后２４小时仍然明显高于正常。胆碱于伤后３小时已有明显升高，２４小时达高峰（Ｐ＜０．０１）。Ｎ－乙酰门冬氨酸含量自伤后３小时明显降低，伤后２４～１６８小时仍然显著低于正常（Ｐ＜０．０１）。谷氨酸自伤后３０分钟开始明显降低，３小时降到最低水平（Ｐ＜０．０１）。结论：实验表明颅脑损伤后３小时伤区脑组织已显著呈缺血性改变，伤后２４小时达高峰。     

Prospective memory in patients with closed head injury: a review

This paper aimed to review the limited, but growing literature on prospective memory (PM) following closed head injury (CHI). Search of two commonly used databases yielded studies that could be classified as: self- or other-report of PM deficits; behavioral PM measures in adults with CHI, behavioral PM measures in children and adolescents with CHI, and treatment of PM in adults with CHI. The methodology and findings of these studies were critically reviewed and discussed. Because of the small number of studies, meta-analysis was only conducted for studies that used behavioral PM measures in adults to integrate findings. PM deficits were found to be commonly reported by patients with CHI and their significant others and they could be identified using behavioral measures in adults, children and adolescents with CHI. However, more work is needed to clarify the nature and mechanisms of these deficits. Although some promising results have been reported by studies that evaluated PM treatment, most studies lack tight experimental control and used only a small number of participants. The paper concluded with some suggestions for future research.     

A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury

Although apolipoprotein E4 (APOE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, the presence of the APOE4 allele is also associated with poor outcome after acute brain injury. One mechanism by which apoE may influence neurological outcome is by downregulating the neuroinflammatory response. Because it does not readily cross the blood-brain barrier, the apoE holoprotein has limited therapeutic potential. We demonstrate that a single intravenous injection of a small peptide derived from the apoE receptor binding region crosses the blood-brain barrier and significantly improves histological and functional outcomes after traumatic brain injury (TBI). The development of an apoE-based intervention represents a novel therapeutic strategy in the management of acute brain injury.     

Heightened false memory: a long-term sequela of severe closed head injury

Declarative memory impairment is a common long-term sequela of severe closed head injury (CHI). Although veridical memory performance following severe CHI has received attention in the literature, little is known about false memory production in this population. Within the present study, both long-term survivors of severe CHI and matched control participants studied and were tested on six 12-items word lists from the Deese Roediger McDermott (DRM) paradigm. Word lists from the DRM are composed of words that are strongly semantically associated to a non-presented word (i.e., the critical lure). Prior studies have shown that healthy young adults show a high level of false recall and recognition memory for the critical lures, and it was hypothesized individuals with severe CHI would show heightened susceptibility to false memory compared to control participants due to difficulty with monitoring of memory. It was further hypothesized that severe CHI participants would show high confidence in their false memories. Consistent with hypotheses, results indicated that although severe CHI participants remembered fewer actual list items, they made more semantically related intrusion errors (recall) and false-positive responses (recognition) than the control participants. Severe CHI participants also showed greater confidence in their false memories than did control participants. The results are interpreted in the context of theoretical accounts of false memory, and possible structural and functional brain changes that might account for the Severe CHI group's memory performance are discussed.     

Hemispheric cerebrovascular venous thrombosis due to closed head injury

Case report We present the case of an 8-month-old infant who was admitted to our Neurosurgery Department with venous infarction related to sagittal sinus thrombosis. The infarction was radiologically detected 5 days after the baby had undergone surgery for acute subdural hematoma due to a closed head injury.Results and conclusions Cerebrovascular venous thrombosis is a rare clinical entity that has multiple causes and variable presenting symptoms. There is no consensus on overall strategy concerning surgical, radiosurgical, or medical therapy (anti-coagulation, thrombolytic, and anti-edema treatment), and exactly how, when, or in which cases these should be applied. The treatment planning should be based on clinical findings, and should be modified according to the clinical course. In this case, the clinical and radiological findings regressed with symptomatic treatment alone.     

Neuropathological investigation of cerebral white matter lesions caused by closed head injury

In order to ascertain whether there is widespread axonal disruption of cerebral white matter in the so‐called ‘diffuse axonal injury’ (DAI), a type of closed head injury, proposed by Adams et al. the author investigated his own cases clinicopathologically. Twenty‐six male autopsied cases of head injury, aged between 19 and 84, 15 of which had sustained road traffic accidents, were examined; the others were due to falling from heights and so on. The study group all belonged to non‐missile head injuries and included 12 cases of diffuse brain injury, as well as 14 cases of focal brain injury, according to the classification of Gennarelli et al. The survival time ranged from 2 h to 21 years. Formalin‐fixed brains were cut coronally so as to make paraffin‐embedded hemispheric sections. Then these sections were stained conventionally (HE, Bodian, Kluver‐Barrera and Holzer) and immunohistochemically (GFAP) to assess axonal decrease, myelin pallor and gliosis by the use of light microscopy. In the 13 chronic cases that died more than 1 month after the accidents, the intensities of gliosis, myelin pallor and axonal decrease tended to correlate with each other. In the 13 acute cases who died less than 1 month after their accident, the degree of axonal decrease in white matter seemed to correlate with the severity of myelin pallor. Regardless of types of trauma, however, axonal retraction balls, the so‐called hallmark of DAI, were found only with myelin pallor suggesting the presence of brain swelling after the injury. Therefore these findings indicate that it may be difficult to accept the notion of DAI, that is, the presence of axonal retraction balls without brain swelling. In addition, diffuse vascular injury (2 cases) as well as rarefaction of subcortical white matter (6 cases) were presented and their pathogenesis individually discussed based on a literature review.     

急进高原轻-中度闭合性颅脑损伤后在不同海拔下伤情变化的观察

目的观察急进高原地区轻-中度闭合性颅脑损伤(mmCHI)急性期转运至不同海拔高度下的伤情变化。 方法平原饲养的健康雄性SD大鼠称基础体质量,模拟海拔6.0 km持续低压、低氧处理24 h后再次称质量,采用气动式撞击装置制作mmCHI模型,观察大鼠致伤后生命体征变化并进行神经功能缺损评分（NSS）,随机分为不同海拔高度组（6.0、4.5、3.0 km）进行观察,并分别对相应海拔高度下大鼠在mmCHI后6、12、24 h的NSS评分、体质量、脑含水量、脑含水量与体质量的比值及颅脑MRI检查。 结果急进高原mmCHI大鼠在致伤后6 h各海拔高度组NSS评分减少值明显低于伤后12、24 h评分减少值（P<0.05）;伤后快速下降至3.0 km组大鼠体质量下降最少,与伤后滞留于6.0 km及下降至4.5 km组比较,差异具有显著统计学意义（P<0.05）;伤后脑含水量各组比较差异无统计学意义;伤后下降至4.5 km大鼠的脑含水量占体质量的百分比最低,与其他2组比较差异具有显著统计学意义（P<0.05）;动态MRI定量检测分析结果显示伤后下降至4.5 km大鼠的胼胝体水肿及脑室扩张程度明显低于其他海拔高度（P<0.05）。 结论极高海拔环境下mmCHI后早期、阶梯式转运至低海拔地区可减轻继发性颅脑损伤。高原颅脑损伤后早期MRI检查可对预后判断及临床诊治有指导意义。     

Acute transient cerebellar dysfunction and stuttering following mild closed head injury

Introduction A wide range of pathologies can cause cerebellar dysfunction but there have been few reports of transient dysfunction after mild head injury. There are none describing stuttering as an acute symptom after such injuries.Case report We report a 12-year-old boy who presented with headache, stuttering speech and truncal and bilateral peripheral cerebellar dysfunction after falling prone from his skateboard. Computed tomographic brain imaging showed normal results. All clinical symptoms and signs had resolved within 24 h obviating further investigation. A follow up clinical interview and examination 4 weeks later revealed no recurrence of cerebellar or speech dysfunction.Conclusion This is the first reported case of acute transient cerebellar dysfunction and stuttering after mild closed head injury. Neurogenic causes for stuttering are increasingly being recognised.     

鼠侧向液压脑损伤后脑血流量和葡萄糖利用率的改变

目的：探讨液压冲击脑损伤后脑血流量（ＣＢＦ），局部脑血流量（ｒＣＢＦ）与局部葡萄糖利用率（ｒＣＧＵ）的变化及其对神经元继发性损伤的影响。方法：应用激光多普勒流量计和定量放射自显影技术。结果：液压冲击脑损伤导致６０秒内ＣＢＦ短暂升高然后显著下降，且持续６０分钟低于正常，同侧和对侧大脑半球的ＣＢＦ相应降为正常值的７９％和９３％。外伤后１小时，损伤侧脑皮层，丘脑及海马的ｒＣＢＦ下降１２％～５９％，对侧大脑半球相应区域则下降１０％～４０％。相反，ｒＣＧＵ在冲击区周围脑皮质及同侧丘脑和海马区升高２７％～１０１％，在对侧大脑半球相应区域则升高２０％～９１％，海马区由液压冲击引起的ｒＣＢＦ和ｒＣＧＵ分离性变化十分显著，同侧海马ＣＡ１和ＣＡ２－３区存活的神经元数量在损伤后两星期时显著减少。结论：ｒＣＢＦ和ｒＣＧＵ的分离性变化是引起外伤后神经元尤其是海马区神经元继发损伤的主要因素。     

Changes of sympatho-adrenal and hypothalamo-pituitary-adrenocortical system in patients with head injury

To determine the role of the sympatho-adrenal (SAS) and hypothalamo-pituitary-adrenocortical system (HPAS) after head injury, the relationship between venous blood epinephrine (E), norepinephrine (NE), adrenocorticotropic hormone (ACTH), Cortisol levels, and clinical condition was examined in 55 patients. These observations suggest that head injury causes mainly activation of the above-mentioned systems depending on the severity of trauma. An inverse correlation between the levels of E, NE and Glasgow Coma Scale score, indicating the severity of head injury was revealed. ACTH and Cortisol were similarly related to the clinical condition, although the observed correlation was less expressed. The changes in hormonal levels were present during the whole research period (1 week), although a certain shift to normalization was observed. However, catecholamines and ACTH levels in plasma were relatively low in severely head-injured patients whose CT scans revealed serious alterations in the mesencephalic-diencephalic area. At the same time their Cortisol levels obtained maximal values and their chance to survive was diminutive. The results of this study indicate that investigation of hormones of SAS and HPAS might be useful as an additional method in the complex of ordinary examinations in establishing early prognosis in patients with brain injury.     

Cerebroprotective effect of stable nitroxide radicals in closed head injury in the rat

Nitroxide stable radicals are unreactive toward most diamagnetic molecules, but readily undergo one-electron redox reactions with paramagnetic species such as free radicals and transition metals, thus serving as cell permeable antioxidants. The involvement of reactive oxygen species in the pathophysiology of neurotrauma has been well established. The neuroprotective properties of three nitroxides: 2,2,6,6-tetramethylpiperidine-1-N-oxyl (TPO), the hydrophilic analog: TPL, and its reduced form: TPH, were tested in a rat model of closed head injury (CHI). CHI was induced in ether anesthetized rats by a weight drop device and recovery was followed for up to 24 h. The ‘clinical status’ was evaluated according to a ‘Neurological Severity Score’ (NSS), at 1 h and 24 h, the difference between these scores, ΔNSS, reflecting the extent of recovery. Edema was assessed by measurement of water content at 24 h. The integrity of the blood-brain barrier (BBB) was investigated using Evans Blue extravasation. TPL, TPH and TPO facilitated clinical recovery, the latter causing a more pronounced effect (ΔNSS = 7.63 ± 0.26 in treated rats vs 4.94 ± 0.48 in control rats, P < 0.001). TPL was found to significantly reduce edema formation (80.13% ± 0.26 vs 83.65% ± 0.49, P < 0.001) and to ameliorate BBB disruption (P < 0.001). The therapeutic window of TPL was found to be in the range of 4 h after CHI. The mechanisms underlying the nitroxide neuroprotective activity presumably involve: (a) reoxidation of reduced transition metal ions; (b) a selective radical-radical reaction; and (c) catalytic removal of intracellular and extracellular O₂⁻. The results indicate that nitroxides could be used in neuroprotective treatment of CHI.     

The glial reaction in closed head injuries

The development of the glial reaction in human closed head injury has been investigated using morphometry and statistical analysis. The brains of eight individuals that survived less than 48 h following closed head injury were analysed using immunoperoxidase for glial fibrillary acidic protein (GFAP). Controls were eight patients without neurological disease. The density of reactive astrocytes was estimated in 25 fields in each of 10 different areas sampled bilaterally avoiding the subpial and subependymal zones, and the perivascular white matter. There was great variation between the zones within and between groups, and considerable variation between individuals. The raw data were expressed as logarithms averaged and analysed using the median and non-parametric statistics. The corpus callosum in the head injury group showed the highest densities of reactive astrocytes, particularly in the splenium which achieved statistical significance using the non-parametric tests. This pattern was not reproduced in the control group. Although there was overlap between the head injured and control individuals, the head injury group had relatively higher densities in all zones, and showed an overall increase in the density of reactive astrocytes. This achieved statistical significance in the corpus callosum, the occipital subcortical white matter, and the cerebellum. This study has shown that the glial reaction is often prominent in the corpus callosum irrespective of the presence of a primary lesion although the pattern varies from case to case.     

Long-term sequelae of brain damage from closed head injury in children and adolescents

A study was made of the sequelae of brain damage in young patients. Seventy patients between 4 and 18 years, admitted under the diagnosis “diffuse brain contusion”, have been followed at least two years after head injury. The degree of function impairment in the fields of motor skills, cognition and behaviour was recorded. It was found that many patients with neurologically little or no function loss, nevertheless after the accident did suffer from psychosocial problems in the realm of family life, school or profession. Based on these findings, the authors recommend a consequent and systematic follow up of patients if they have been in coma for more than 1 hour, the objective being the early assessment of such dysfunctions, followed by adequate assistence.