Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury

Diffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and gray matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2 h) and the sub-acute (7 days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum. Post-hoc tests indicated acute changes in mean diffusivity (MD) in the bilateral cortex and hippocampus (p < 0.0005) and fractional anisotropy (FA) in ipsilateral cortex (p < 0.0005), hippocampus (p = 0.014), corpus callosum (p = 0.031) and contralateral external capsule (p = 0.011). These changes returned to baseline by the sub-acute stage. However, mean kurtosis (MK) was significantly elevated at the sub-acute stages in all ipsilateral regions and scaled inversely with the distance from the impacted site (cortex and corpus callosum: p < 0.0005; external capsule: p = 0.003; hippocampus: p = 0.011). Further, at the sub-acute stage increased MK was also observed in the contralateral regions compared to baseline (cortex: p = 0.032; hippocampus: p = 0.039) while no change was observed with MD and FA. An increase in mean kurtosis was associated with increased reactive astrogliosis from immunohistochemistry analysis. Our results suggest that DKI is sensitive to microstructural changes associated with reactive astrogliosis which may be missed by standard DTI parameters alone. Monitoring changes in MK allows the investigation of molecular and morphological changes in vivo due to reactive astrogliosis and may complement information available from standard DTI parameters. To date the use of diffusion tensor imaging has been limited to study changes in white matter integrity following traumatic insults. Given the sensitivity of DKI to detect microstructural changes even in the gray matter in vivo, allows the extension of the technique to understand patho-morphological changes in the whole brain following a traumatic insult.     

Common data elements in radiologic imaging of traumatic brain injury

Duhaime AC, Gean AD, Haacke EM, Hicks R, Wintermark M, Mukherjee P, Brody D, Latour L, Riedy G, Common Data Elements Neuroimaging Working Group Members, Pediatric Working Group Members. Common data elements in radiologic imaging of traumatic brain injury.Radiologic brain imaging is the most useful means of visualizing and categorizing the location, nature, and degree of damage to the central nervous system sustained by patients with traumatic brain injury (TBI). In addition to determining acute patient management and prognosis, imaging is crucial for the characterization and classification of injuries for natural history studies and clinical trials. This article is the initial result of a workshop convened by multiple national health care agencies in March 2009 to begin to make recommendations for potential data elements dealing with specific radiologic features and definitions needed to characterize injuries, as well as specific techniques and parameters needed to optimize radiologic data acquisition. The neuroimaging work group included professionals with expertise in basic imaging research and physics, clinical neuroradiology, neurosurgery, neurology, physiatry, psychiatry, TBI research, and research database formation. This article outlines the rationale and overview of their specific recommendations. In addition, we review the contributions of various imaging modalities to the understanding of TBI and the general principles needed for database flexibility and evolution over time to accommodate technical advances.     

轻度创伤性脑损伤后磁敏感加权成像脑内微出血与外伤后抑郁发生的相关性

目的:探讨轻度创伤性脑损伤后磁敏感加权成像(SWI)脑内微出血与创伤后新发抑郁症之间的关系。方法:常规CT和MRI检查无明显异常的轻度创伤性脑损伤(TBI)患者行MRI检查,包括常规MR序列和SWI序列。半自动勾勒和手动计数微出血病变的数量和体积。所有患者在TBI后1年内接受DSM-Ⅳ-TR轴Ⅰ障碍临床定式检查(SCID-Ⅳ)。结果:抑郁组SWI微出血病变发生率高于非抑郁组(P0.001)。在显示出微血管病变的患者中,抑郁组微出血病变数量和体积大于非抑郁组(P0.001)。这些病变的数量和体积的差异只存在于在额叶、顶叶和颞叶(P0.001)。在显示出微血管病变的患者中,其他区域的病变数量和体积在抑郁和非抑郁组之间差异无统计学意义。结论:SWI可用于诊断轻度TBI后的微出血病变,病灶的分布范围和位置与TBI后抑郁相关。     

急性脑创伤时血清抵抗素及内脂素含量变化的研究

目的 检测急性颅脑创伤后患者外周血抵抗素 （resistin）和内脂素（visfatin）水平的含量变化,探讨其临床意义.方法 选择120例不同病情的急性颅脑创伤患者作为研究对象,60例健康体检者作为对照组.采用酶联免疫法（ELISA）检测血清中抵抗素和内脂素的含量.应用SPSS11.0软件统计处理,组间比较采用One-way ANOVA.结果 急性颅脑创伤患者血清抵抗素和内脂素含量明显高于正常对照组（P〈0.01）,且均与病情呈正相关;抵抗素和内脂素含量在入院当天即达到较高水平,3d达到高峰,以后逐渐上升;患者抵抗素水平与内脂素呈正相关（r=0.72, P〈0.01）.结论 急性颅脑创伤患者外周血抵抗素和内脂素含量的变化与病情严重程度密切相关.     

Robust whole-brain segmentation: Application to traumatic brain injury

We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called “Multi-Atlas Label Propagation with Expectation–Maximisation based refinement” (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to differentiate subjects with the presence of a mass lesion or midline shift from those with diffuse brain injury with 76.0% accuracy. The thalamus, putamen, pallidum and hippocampus are particularly affected. Their involvement predicts TBI disease progression.     

颅脑创伤型下丘脑垂体功能不全的临床研究

目的 研究颅脑创伤(TBI)后垂体前叶激素(APHs)、甲状腺功能(TF)和生殖激素(GnH)的动态变化及其临床意义. 方法 随机对浙江省人民医院2006年3月至2007年6月经系列头颅CT扫描和/或MRI检查,明确无下丘脑、垂体等部位的原发损伤,且既往无中枢神经系统、内分泌和泌尿生殖系统肿瘤及免疫性疾患史的93例门急诊和住院TBI患者的APHs、TF和GnH进行测定,并按患者的GCS评分、TBI类型和损伤程度以及有无继发性脑损害等因素进行分组研究,以同期20例健康体检者作为对照组.采用SPSS 11.5软件进行分析,多变量采用成组Hotelling T2检验,两组均数间比较采用t检验,P<0.05为差异具有统计学意义. 结果 93例患者人院就诊时的促肾上腺皮质激素(ACTH)、黄体生成素(LH)和泌乳素(PRL)水平明显高于出院随访期和对照组(P<0.05),促甲状腺素(TSH)和甲状腺激素T3、T4和游离T3(FT3)水平则明显低于出院随访期和对照组(P<0.05).有继发性脑损害组的血清ACTH值和PRL值分别高达(33.33±6.86)和(31.74±5.51),GCS 9～12分组的血清LH值为(9.48±1.14);颅脑损伤组的血清TSH值(1.26±0.17)明显低于对照组和其他各组(P<0.05).除TSH、PRL、睾酮(T)和雌二醇(E2),患者出院随访期其他血清APHs值均明显低于正常对照组(P<0.05).单项APH水平低下的创伤型下丘脑垂体功能不全(THPI)的发生率为13.8%,同时累及3种以上APHs的THPI发生率仅为3.2%;正常甲状腺功能病态综合征(SETS)的发生率为14.0%. 结论 THPI以单项APH分泌障碍型多见.颅脑创伤所致的急性颅内高压以及脑水肿、脑缺血等继发性脑损害可能是导致删的主要原因;TBI后早期的高PRL血症是提示THPI的重要指标,TBI后激素水平的动态变化可作为激素疗法的重要依据.     

Prediction of memory rehabilitation outcomes in traumatic brain injury by using functional magnetic resonance imaging

Strangman GE, O'Neil-Pirozzi TM, Goldstein R, Kelkar K, Katz DI, Burke D, Rauch SL, Savage CR, Glenn MB. Prediction of memory rehabilitation outcomes in traumatic brain injury by using functional magnetic resonance imaging.

Objective

To evaluate the ability of functional magnetic resonance imaging (fMRI) measures collected from people with traumatic brain injury (TBI) to provide predictive value for rehabilitation outcomes over and above standard predictors.

Design

Prospective study.

Setting

Academic medical center.

Participants

Persons (N=54) with TBI greater than 1 year postinjury.

Intervention

A novel 12-session group rehabilitation program focusing on internal strategies to improve memory.

Main Outcome Measure

The Hopkins Verbal Learning Test−Revised (HVLT-R) delayed recall score.

Results

fMRI measures were collected while participants performed a strategically directed word memorization task. Prediction models were multiple linear regressions with the following primary predictors of outcome: age, education, injury severity, preintervention HVLT-R, and task-related fMRI activation of the left dorsolateral and left ventrolateral prefrontal cortex (VLPFC). Baseline HVLT-R was a significant predictor of outcome (P=.007), as was injury severity (for severe vs mild, P=.049). We also found a significant quadratic (inverted-U) effect of fMRI in the VLPFC (P=.007).

Conclusions

This study supports previous evidence that left prefrontal activity is related to strategic verbal learning, and the magnitude of this activation predicted success in response to cognitive memory rehabilitation strategies. Extreme under- or overactivation of VLPFC was associated with less successful learning after rehabilitation. Further study is necessary to clarify this relationship and to expand and optimize the possible uses of functional imaging to guide rehabilitation therapies.     

Long-term survival following traumatic brain injury

Purpose.?The study used a retrospective cohort design to establish long-term mortality rates and predictors of mortality for persons after moderate to severe traumatic brain injury (TBI).

Method.?Consecutive records of persons with moderate to severe TBI who were discharged from a large rehabilitation hospital in Pittsburgh, Pennsylvania in the years 1974?–?1984, 1988 and 1989 were reviewed.

Results.?Six hundred and forty-two eligible individuals were identified and mortality was ascertained up to 24 years post injury. One hundred and twenty-eight of these individuals were found to be deceased. Poisson regression analyses revealed at least a 2-fold increased risk for mortality compared to the general population. Pre-injury characteristics and levels of disability at discharge from in-patient rehabilitation were among the strongest predictors of mortality.

Conclusions.?These data constitute evidence for premature death in the post-acute TBI population following a moderate to severe head injury and are discussed in relation to other research in the area.     

Return to work following traumatic brain injury: trends and challenges

Purpose. The aim of this paper is to present the current knowledge regarding return to work (RTW) following traumatic brain injury (TBI).

Method. Based on a Medline search, the authors reviewed the current TBI rehabilitation literature regarding (a) predictive factors for successful RTW, and (b) current concepts in rehabilitative strategies for successful RTW.

Results. The functional consequences to the victim of traumatic brain injury (TBI) can be severe. Intensive rehabilitative efforts typically emphasize the early phase and address mainly the accompanying functional deficits in the realm of basic activities of daily living and mobility. An otherwise successful medical rehabilitation may end unsuccessfully because of the failure to return to work, with profound consequences to the individual and family, both economic and psychosocial. Even mild TBI may cause lasting problems in tasks calling for sustained attention. There appears to be a complex interaction between pre-morbid characteristics, injury factors, post injury impairments, personal and environmental factors in TBI patients, which influences RTW outcomes in ways that make prediction difficult. Injury severity and lack of self-awareness appear to be the most significant indicators of failure to RTW. Several medical, psychosocial and rehabilitative therapies are currently being implemented in rehabilitation settings which improve the chances of returning to work.

Conclusion. Accurate prediction of whether a particular TBI patient will successfully return to work is not feasible, with RTW rates in the 12 - 70% range. A significant proportion of TBI patients, including those who are severely injured, are able to return to productive employment if sufficient and appropriate effort is invested. A comprehensive approach - medical and psychosocial - eventually entailing adequate vocational rehabilitation with supported employment can improve outcomes.     

Return to work following traumatic brain injury: Trends and challenges

Purpose. The aim of this paper is to present the current knowledge regarding return to work (RTW) following traumatic brain injury (TBI).

Method. Based on a Medline search, the authors reviewed the current TBI rehabilitation literature regarding (a) predictive factors for successful RTW, and (b) current concepts in rehabilitative strategies for successful RTW.

Results. The functional consequences to the victim of traumatic brain injury (TBI) can be severe. Intensive rehabilitative efforts typically emphasize the early phase and address mainly the accompanying functional deficits in the realm of basic activities of daily living and mobility. An otherwise successful medical rehabilitation may end unsuccessfully because of the failure to return to work, with profound consequences to the individual and family, both economic and psychosocial. Even mild TBI may cause lasting problems in tasks calling for sustained attention. There appears to be a complex interaction between pre-morbid characteristics, injury factors, post injury impairments, personal and environmental factors in TBI patients, which influences RTW outcomes in ways that make prediction difficult. Injury severity and lack of self-awareness appear to be the most significant indicators of failure to RTW. Several medical, psychosocial and rehabilitative therapies are currently being implemented in rehabilitation settings which improve the chances of returning to work.

Conclusion. Accurate prediction of whether a particular TBI patient will successfully return to work is not feasible, with RTW rates in the 12 – 70% range. A significant proportion of TBI patients, including those who are severely injured, are able to return to productive employment if sufficient and appropriate effort is invested. A comprehensive approach – medical and psychosocial – eventually entailing adequate vocational rehabilitation with supported employment can improve outcomes.     

Contemporary view on neuromonitoring following severe traumatic brain injury

Evolving brain damage following traumatic brain injury (TBI) is strongly influenced by complex pathophysiologic cascades including local as well as systemic influences. To successfully prevent secondary progression of the primary damage we must actively search and identify secondary insults e.g. hypoxia, hypotension, uncontrolled hyperventilation, anemia, and hypoglycemia, which are known to aggravate existing brain damage. For this, we must rely on specific cerebral monitoring. Only then can we unmask changes which otherwise would remain hidden, and prevent adequate intensive care treatment. Apart from intracranial pressure (ICP) and calculated cerebral perfusion pressure (CPP), extended neuromonitoring (SjvO₂, ptiO₂, microdialysis, transcranial Doppler sonography, electrocorticography) also allows us to define individual pathologic ICP and CPP levels. This, in turn, will support our therapeutic decision-making and also allow a more individualized and flexible treatment concept for each patient. For this, however, we need to learn to integrate several dimensions with their own possible treatment options into a complete picture. The present review summarizes the current understanding of extended neuromonitoring to guide therapeutic interventions with the aim of improving intensive care treatment following severe TBI, which is the basis for ameliorated outcome.     

急性脑损伤时内脂素和超敏C-反应蛋白的变化

目的 检测急性颅脑损伤后患者外周血内脂素和超敏C-反应蛋白(hs-CRP)水平的动态变化,探讨其临床意义.方法 120例急性脑损伤患者均为滕州市中心人民医院神经外科及ICU科2009年8月至2010年6月收治住院的患者,其中男60例,女 60例,年龄(43.2±6.2)岁.所有患者均符合颅脑损伤诊断标准.根据入院时格拉斯哥评分(GCS)将患者分为轻度(13～15分)40例,中度(9～12分)40例,重度(3～8分)40例.60例健康体检人员作为对照,其中男30例,女30例,年龄(42.2±6.7)岁.患者于入院后12 h内(即0时间点)及1,3,7,15 d空腹抽取静脉血3 mL用于检测外周血hs-CRP和内脂素的含量变化.结果 急性颅脑损伤患者血清hs-CRP水平均显著高于正常人对照组(3.05±2.08)mg/L(P＜0.01),且患者hs-CRP水平与病情呈正相关;急性颅脑损伤患者血清内脂素含量明显高于正常对照组(17.61±2.45)μg/L(P＜0.01),与病情呈正相关;各组患者在入院当天hs-CRP水平有所升高,并在入院后继续升高,hs-CRP在1 d达高峰,3 d开始下降;内脂素含量在入院当天有所升高,3 d达到高峰,以后逐渐上升;患者内脂素水平与hs-CRP呈正相关(r=0.63,P＜0.01).结论 急性颅脑损伤患者外周血内脂素和hs-CRP水平的变化与病情严重程度密切相关.     

创伤性颅脑损伤后神经细胞凋亡的研究

目的：通过对创伤性颅脑损伤后神经细胞凋亡的研究，了解人脑创伤后脑组织中凋亡发生的情况及其所起的作用。方法：采用末端脱氧核苷酸转移酶介导的d-UTP生物素标记法(TUNEL法)检测细胞凋亡。同时显微镜观察病理切片。结果：66．7％出现TUNEL阳性，TUNEL阳性与阴性患者间的GCS评分(t=-2.88，P=O．01)、受伤时间(t=2．14，P=0．049)有显著差异。TUNEL阳性与阴性患者间性别、年龄、预后无显著差异。结论：人脑创伤后脑组织中存在凋亡，且与患者的病情严重程度及病程相关。其在颅脑创伤的病理过程中有一定作用，但只是颅脑损伤后复杂病理过程中的一种表现，即创伤后神经细胞死亡的一种方式。     

CT灌注成像对颅脑损伤术后脑微循环障碍的早期诊断价值

目的探讨重型颅脑损伤术后CT灌注成像在评价脑微循环方面的应用价值。方法选择12例颅脑损伤患者在术后6～20h内行常规CT和CT灌注成像检查。结果早期常规头颅CT平扫,除颅脑损伤征象和术后改变外,无缺血表现7例;脑实质低密度缺血灶5例,占41．67％。11例患者的灌注参数图像[局部脑血流量（rCBF）、局部脑血容量（rCBV）、平均通过时间（MTT）]都有明确的异常表现,占91．67％,1例无变化。结论灌注CT能够在重型颅脑损伤术后早期显示脑组织灌注部位、范围及缺血程度,确定脑梗死的存在及灌注情况,并可进行定量研究,对临床早期选择预防脑梗死治疗方案具有一定的指导价值。可以作为指导治疗的一个指标。但受到病人病情、扫描时间、影像技术人员技术水平的影响。     

大鼠创伤性脑损伤早期基因差异表达的研究

目的研究创伤性脑损伤早期基因表达谱与正常脑组织基因表达谱的差异,以期阐明脑损伤后早期基因表达的改变规律,阐明脑损伤发生发展的分子机制,从而为临床治疗提供帮助,同时为法医损伤时间推断研究寻找标志物提供帮助。方法以大鼠自由落体损伤模型为对象,从损伤区脑组织和假手术对照组脑组织分别提取mRNA,经反转录成cDNA后与含有4096个随机基因的基因表达谱芯片杂交,杂交后的芯片经扫描仪扫描,并用GenePix3.0软件分析结果。结果发现有124个差异表达基因或表达序列标签（expression sequencetags,ESTs）;其中有46个基因和26个EST表达下调;28个基因和24个EST表达上调;在这些表达有差异的基因中,有涉及细胞内信号传导、神经递质释放、参与炎症的蛋白、离子通道及其受体蛋白和参与炎症反应的蛋白等被发现。结论创伤性脑损伤的发生发展涉及多个基因的改变;研究一个或少数几个基因很难解释其损伤后分子变化机制;基因芯片是研究颅脑损伤这种多基因改变、多因素作用的理想工具。     

轻度创伤性脑损伤的扩散张量成像研究

目的探讨MR扩散张量成像（DTI）对轻度创伤性脑损伤（m TBI）的诊断价值。材料与方法对35例轻度m TBI患者（病例组）和15名健康对照者（对照组）分别行常规MR、DTI检查。选择双侧额叶白质、双侧内囊区、胼胝体膝部及压部中线位置各一个点（共6个）为感兴趣区,分别测定FA值、ADC值。将病例组与对照组各部位的FA值、ADC值进行统计学分析。结果病例组与对照组间各部位ADC值均无显著性差异。双侧额叶白质区、双侧内囊区及胼胝体压部FA值病例组与对照组均有统计学差异（P〈0.05）。结论 FA值能定量测定轻度创伤性脑损伤后脑组织水分子代谢的情况,DTI可以作为一项客观指标,定量评估轻度脑外伤患者的病情,并为对病情发展和预后的观察带来可能。     

自闭症儿童脑结构的MRI研究

目的通过MRI研究自闭症儿童的脑结构异常。方法对26例自闭症儿童和16例正常儿童进行脑部磁共振扫描,比较两组全脑各向异性分散(FA)的差异,分析自闭症儿童各被检测部位的FA值与儿童行为评估量表(CBQ-R)得分的相关性。结果 (1)自闭症组右侧额下回、左侧额中回、右侧颞下回邻近白质的FA值(0.32±0.12、0.28±0.03、0.17±0.09)低于对照组(0.76±0.08、0.57±0.01、0.61±0.36),P<0.05;自闭症组左顶小叶邻近白质的FA值(0.75±0.47)高于对照组(0.42±0.90),P<0.05。(2)自闭症组右侧胼胝体压部FA值与CBQ-R的语言评分值呈负相关(r=-0.419,P<0.05)。(3)自闭症组内囊后肢、胼胝体膝部FA值高于对照组,差异有统计学意义(P<0.05)。结论自闭症儿童的多个脑部位的白质纤维的完整性遭到破坏,胼胝体神经纤维连接存在异常。     

氢质子磁共振波谱对创伤性脑损伤的分析

目的探讨氢质子磁共振波谱(1Hmagneticresonancespectroscopy1HMRS)分析对创伤性脑损伤(traumaticbraininjuryTBI)受伤程度、预后预测的临床价值。方法对25例TBI患者和10例正常志愿者进行1HMRS检查,观察患者与正常对照组及患者患侧与正常侧间N-乙酰天门冬氨酸(NAA)、胆碱(Cho)肌酸(Cr)、乳酸(Lac)及NAA/Cr、NAA/Cho、Cho/Cr值的变化,分析这些指标与格拉斯哥昏迷评分(GCS)及格拉斯哥预后评分(GOS)的相关性;结果TBI患者较正常对照组及其患者患侧脑白质较对侧同一位置常规MRI检查表现正常脑白质(nomal-appearingwhitematterNAWM)的NAA/Cho、NAA/Cr值下降更明显,而Cho/Cr值上升更明显;出现Lac水平上升患者的GCS为重度,其预后不良,NAA/Cr、NAA/Cho、Cho/Cr值变化与TBI患者GCS、GOS存在相关性;结论1HMRS对脑外伤的程度及预后预测有重要价值。     

鼻咽癌放疗后脑损伤MR功能成像研究进展

放射治疗是鼻咽癌的首选治疗方法.尽管放疗技术不断提高,但鼻咽癌的放疗仍不可避免地会对正常组织造成不同程度的损害,放射性脑损伤是鼻咽癌放疗后最常见的并发症之一,严重影响了患者生活质量,所以对放射性脑损伤的早期诊断就显得尤为重要.多种功能MRI技术的快速发展,为鼻咽癌放疗后脑损伤的早期诊断提供了新方法.     

Early ventilation in traumatic brain injury

While airway and ventilatory compromise are significant concerns following traumatic brain injury (TBI), there is little data supporting an aggressive approach to airway management by prehospital personnel, and a growing number of reports suggesting an association between early intubation and increased mortality. Recent clinical and experimental data suggest that hyperventilation is an important contributor to these adverse outcomes in TBI patients. Various mechanisms appear to be responsible for the worsened outcomes, including hemodynamic, cerebrovascular, immunologic and cellular effects. Here, relevant experimental and clinical data regarding the impact of ventilation on TBI are reviewed. In addition, experimental data regarding potential mechanisms for the adverse effects of hyperventilation and hypocapnia on the injured brain are presented. Finally, the limited data regarding the impact of hypoventilation and hypercapnia on outcome from TBI are discussed.