大鼠轻型颅脑损伤后星形胶质细胞与神经元的病理改变

目的 探讨轻型颅脑损伤（TBI）后神经元及星形胶质细胞改变的病理生理过程。方法 将24只成年SD大鼠随机分为轻型TBI组（n=18）和假手术组（n=6）,轻型TBI组又分为伤后3 h（n=6）、伤后24 h（n=6）、伤后72 h（n=6）三亚组。采用液压冲击法制作轻型TBI模型。采用胶质纤维酸性蛋白（GFAP）染色检测星形胶质细胞,采用Fluoro-Jade B（FJ-B）荧光染色检测变性神经元。结果 与假手术组相比,轻型TBI后3 h、24 h、72 h邻近顶叶皮质、海马CA2/3区GFAP阳性细胞数量均明显减少（P<0.05）;缺失区周围星形胶质细胞肿胀增生明显。FJ-B阳性神经元在损伤后3 h无明显增加（P>0.05）,伤后24 h皮层区FJ-B阳性神经元显著增加（P<0.05）,伤后72 h海马区FJ-B阳性神经元显著增加（P<0.05）。伤后72 h伤侧皮层区与海马区GFAP阳性细胞数和FJ-B阳性细胞数呈显著负相关（r=-0.8285,P<0.05）。结论 轻型TBI后星形胶质细胞超急性期（3 h）即出现损害和胶质反应,神经元则在急性期（24 h）至亚急性期（72 h）出现明显损害,星形胶质细胞缺失程度可以反应神经元损伤程度。     

Regional and temporal characterization of neuronal, glial, and axonal response after traumatic brain injury in the mouse

Fluid percussion injury (FPI) is a commonly used and clinically relevant model of traumatic brain injury (TBI) in the rat. Recently, our lab successfully adapted FPI to mice. To account for differences in response to injury between mice and rats and provide a foundation for further use of FPI in gene-targeting studies, we sought to characterize the temporal and regional response to FPI in male C57BL/6 mice. Animals were killed at 10 min, 24 h, and 4, 7, 14, and 35 days (n = 3 for each group) after a very severe parasagittal FPI (> 4.0 atm) or sham injury (n = 3). Extensive numbers of damaged neurons were consistently found in the ipsilateral cortex, thalamus, and hippocampus by 10 min. This damage was nearly identical at 24 h, but quickly declined at subsequent time points. Activated microglia were found only in regions of neuronal injury at the earliest time points. Glial fibrillary acidic protein immunoreactivity reached significantly higher levels compared with controls at 7 days (P < 0.05) in the cortex, thalamus, and hippocampus and remained elevated for 35 days. White matter degeneration was present in all regions examined. This damage did not appear until at least day 4, but progressed up to day 35. The spatial pattern of damage we observed in mice after FPI is similar to that seen in rats. However, the temporal progression of neuronal injury in mice is comparatively abbreviated in the hippocampus and thalamus. In conclusion, these results suggest that FPI in mice may be a particularly useful tool for studying mechanisms of TBI in gene-targeting studies. Received: 13 October 1998 / Revised: 22 February 1999 / Accepted: 24 March 1999     

大鼠脑外伤后自噬被激活并在早期对受损神经元起保护作用

目的研究大鼠脑外伤后自噬是否被激活并探讨其在脑外伤后神经细胞损伤和修复中的作用。方法建立大鼠定量脑外伤模型,于脑外伤后不同时间点处死动物并取脑;应用透射电镜检测脑组织自噬双层膜结构以及次级溶酶体的形成情况;应用白噬标记抗体LC3B和DBeclin-1对脑外伤后不同时间点的脑组织进行免疫荧光和Western blot检测;LC3和caspase-3或Beclin1和Fluoro—Jade双标记检测。结果脑外伤后1h在损伤区周围即检测到双层膜结构,并且一直持续到脑外伤后32天。脑外伤后1h,脑组织中LC3和Beclin-1表达增加,损伤后3天内阳性细胞以神经元为主,之后阳性胶质细胞增加,第8天达到高峰,并可持续至脑外伤后32天仍维持高表达。大多数阳性细胞分布在损伤区周围（包括海马）而不是损伤区。此外,脑外伤后24小时以前,在损伤区周围不是所有的LC3阳性细胞都与caspase-3阳性细胞重叠。同样脑外伤后6h至48h,Beclin1阳性海马神经元与Fluoro—Jade染色不重叠。结论脑外伤后自噬被激活,在损伤后早期保护损伤区周围神经细胞免于凋亡和退行性变,并对神经细胞损伤与修复发挥长期作用。     

Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats

Amyloid precursor protein (APP) has previously been shown to increase following traumatic brain injury (TBI). Whereas a number of investigators assume that increased APP may lead to the production of neurotoxic Abeta and be deleterious to outcome, the soluble alpha form of APP (sAPPalpha) is a product of the non-amyloidogenic cleavage of amyloid precursor protein that has previously been shown in vitro to have many neuroprotective and neurotrophic functions. However, no study to date has addressed whether sAPPalpha may be neuroprotective in vivo. The present study examined the effects of in vivo, posttraumatic sAPPalpha administration on functional motor outcome, cellular apoptosis, and axonal injury following severe impact-acceleration TBI in rats. Intracerebroventricular administration of sAPPalpha at 30 min posttrauma significantly improved motor outcome compared to vehicle-treated controls as assessed using the rotarod task. Immunohistochemical analysis using antibodies directed toward caspase-3 showed that posttraumatic treatment with sAPPalpha significantly reduced the number of apoptotic neuronal perikarya within the hippocampal CA3 region and within the cortex 3 days after injury compared to vehicle-treated animals. Similarly, sAPPalpha-treated animals demonstrated a reduction in axonal injury within the corpus callosum at all time points, with the reduction being significant at both 3 and 7 days postinjury. Our results demonstrate that in vivo administration of sAPPalpha improves functional outcome and reduces neuronal cell loss and axonal injury following severe diffuse TBI in rats. Promotion of APP processing toward sAPPalpha may thus be a novel therapeutic strategy in the treatment of TBI.     

Hippocampal neuronal degeneration in the traumatic brain injury mouse: non-trivial effect of scalp incision

Objectives: In experimental models of traumatic brain injury (TBI), posttraumatic hippocampal neuronal degeneration in the cornu ammonis 1 (CA1), and/or the cornu ammonis 3 (CA3) regions are regarded as the most notable phenotypic appearances relating to the pathophysiology of human post-concussion syndrome. However, these morphological changes are often also seen in subjects without TBI, namely ‘sham’ groups. The frequencies and reasons of appearance of hippocampal neuronal degeneration in mice with TBI and/or sham are not clear.

Methods: We compared the frequencies of hippocampal neuronal degeneration among three groups: TBI (mice with external force impact performed by Marmarou’s weight drop model after scalp incision), sham (mice with scalp incision alone), and control (mice with neither external force impact nor scalp incision), using hematoxylin and eosin stain in day 6 (n = 5 in each group.) Isoflurane was used for anesthesia in all mice.

Results: The frequencies were 80, 100, and 20% in CA1, and 20, 40, and 60% in CA3, for TBI, sham, and control, respectively. In CA1, a significant difference of the frequency was observed between sham and control (p = 0.048), but not, between TBI and sham (p = 1.000) in Fisher’s exact test. In CA3, no significant difference in the frequency was observed between the three groups.

Conclusion: Scalp incision, rather than external impact force, might affect the CA1 hippocampal neuronal degeneration in mice with TBI. In addition, factor(s) other than external impact force or scalp incision may also cause hippocampal neuronal degeneration in both CA1 and CA3. Careful interpretation is needed concerning hippocampal neuronal degeneration induced by a weight drop device observed in mice with TBI.     

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 h and 24 h post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters - axial diffusivity and relative anisotropy - were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose.     

Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury

Traumatic axonal injury (TAI) following traumatic brain injury (TBI) remains a clinical problem for which no effective treatment exists. TAI was thought to involve intraaxonal changes that universally led to impaired axonal transport (IAT), disconnection and axonal bulb formation. However, recent, immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and antibodies to neurofilament compaction (NFC), RM014, demonstrated that NFC typically occurs independent of IAT, indicating the existence of different populations of damaged axons. FK506 administration has been shown to attenuate IAT. However, in light of the above, the ability of FK506 to attenuate axonal damage demonstrating NFC requires evaluation. The current study explored the potential of FK506 to attenuate both populations of damaged axons. Rats were administered FK506 (3 mg/kg) or vehicle 30 min preinjury. Three hours post-TBI, tissue was prepared for the visualization of TAI using antibodies targeting IAT (APP) or NFC (RMO14) or a combined labeling strategy. Confirming previous reports, FK506 treatment reduced the number of axons demonstrating IAT in the CSpT, from 411 +/- 54.70 to 91.00 +/- 33.87 (P 相似文献   

Axonal degeneration promotes abnormal accumulation of amyloid β-protein in ascending gracile tract of gracile axonal dystrophy (GAD) mouse

The GAD mouse is a spontaneous neurological mutant with axonal dystrophy in the gracile tract of the medulla oblongata and spinal cord. The immunoreactivity of amyloid precursor protein (APP-IR) and amyloid β-protein (AβP-IR) was examined in the gracile tract and the dorsal root ganglia of normal and GAD mice. The mice were studied at 4, 9, 18, and 32 weeks of age. These periods correspond clinically to the initial, progressive, critical, and terminal stages of the disease, respectively. The APR-IR in both axons and glial cells was already accentuated to a higher level as early as 4 weeks of age in the gracile nucleus of GAD mouse. Similarly there was increase in APR-IR of GAD mouse in the dorsal root ganglia. Almost all of the primary neurons in the dorsal root ganglia at the lumbar cord level of GAD mouse revealed stronger APP-IR than those of normal mouse throughout all stages. The cells showing immunoreactivity for amyloid β-protein became positive in axons and glial cells in the gracile nucleus by approximately the 9th week, and followed by an increase of AβP-IR in order of the cervical, thoracic and lumbar spinal cords. These results suggest that the initial feature in GAD mouse is an accumulation of amyloid precursor protein induced by axonal dystrophy which then leads to a deposition of amyloid β-protein within the cytoplasm of both axons and glial cells in the gracile tract.     

Cathepsin B contributes to traumatic brain injury‐induced cell death through a mitochondria‐mediated apoptotic pathway

It has been reported that lysosomal proteases play important roles in ischemic and excitotoxic neuronal cell death. We have previously reported that cathepsin B expression increased remarkably after traumatic brain injury (TBI). The present study sought to investigate the effects of a selective cathepsin B inhibitor (CBI) [N‐L‐3‐trans‐prolcarbamoyloxirane‐2‐carbonyl)‐L‐isoleucyl‐L‐proline] on cell death and behavioral deficits in our model. We examined the levels of cathepsin B enzymatic activity and its expression by double labelling damaged cells in the brain slice with propidium iodide (PI) and anticathepsin B. The results showed an elevated enzymatic activity associated with TBI‐induced increase in a mature form of cathepsin B, suggesting that cathepsin B may play a role in TBI‐induced cell injury. PI was found to label cells positive for the neuronal‐specific nuclear marker NeuN, whereas fewer GFAP‐positive cells were labelled by PI, suggesting that neurons are more sensitive to cell death induced by TBI. Additionally, we found that pretreatment with CBI remarkably attenuated TBI‐induced cell death, lesion volume, and motor and cognitive dysfunction. To analyze the mechanism of action of cathepsin B in the cell death signaling pathway, we assessed DNA fragmentation by electrophoresis, Bcl‐2/Bax protein expression levels, Bid cleavage, cytochrome c release, and caspase‐3 activation. The results imply that cathepsin B contributes to TBI‐induced cell death through the present programmed cell necrosis and mitochondria‐mediated apoptotic pathways. © 2010 Wiley‐Liss, Inc.     

Antibodies to the C-terminus of the β-amyloid precursor protein (APP): a site specific marker for the detection of traumatic axonal injury

Antibodies to the amyloid precursor protein (APP) are commonly used to detect traumatic axonal injury (TAI). Carried by fast anterograde axoplasmic transport, APP will pool at regions of impaired transport associated with TAI. Based primarily upon commercial antibody availability, previous studies have targeted the N-terminus of APP, which, with respect to antigen detection, is suboptimally located within anterogradely transported vesicles. Recently, antibodies to the APP C-terminus, located on the external surface of anterogradely transported vesicles, have become available, allowing for the exploration of their utility in detecting TAI. To this end, rats were subjected to an impact acceleration injury, surviving 30 min to 24 h post-injury. They were then perfused, their brains sectioned and prepared for dual label immunofluorescent microscopy, single label bright field microscopy, and electron microscopy (EM). Antibodies to the APP C-terminus yielded the ready detection of intensely labeled TAI with significantly reduced diffuse background staining in comparison to antibodies to the APP N-terminus in both dual label immunofluorescent and single label bright-field approaches. EM examination of antibodies to the APP C-terminus in TAI revealed intense labeling of pooled intra-axonal vesicular profiles, confirming the anterogradely transported vesicular source of the APP seen in TAI. Interestingly, in addition to providing a technically superior approach and new detailed information on the subcellular localization of APP, antibodies to the APP C-terminus also proved more cost effective. Immunofluorescent studies of APP C-terminus immunoreactivity involved 1/3 the cost of targeting the N-terminus, while bright field APP C-terminus studies were performed for 1/20 the cost.     

磁敏感加权成像对轻型颅脑损伤的临床应用及意义

目的探讨MR磁敏感加权成像(SWI)在检测轻型颅脑损伤(MTBI)患者脑内微小出血灶(MBLS)中的应用及其意义。方法应用SWI检测MTBI患者63例,其中有意识障碍者33例,无意识障碍者30例,分析比较两组患者MBLS的分布及患者颅脑损伤后综合征(PTBS)发生率及意义。结果有意识障碍者33例中MBLS者21例(63.6%),其中PTBS13例;而无MBLS者12例,其中PTBS4例。无意识障碍30例中MBLS者9例(30.0%),其中PTBS5例;无MBLS者21例,其中PTBS5例。有意识障碍者中MBLS的发生率均明显高于无意识障碍者(P<0.05)。有MBLS者中PTBS的发生率(60.0%,18/30)明显高于无MBLS者(27.3%,9/33)(P<0.05)。皮层脑组织中MBLS发生率明显高于深部脑组织(P<0.01)。结论 MTBI患者脑组织中存在MBLS,且提示其存在与PTBS密切相关;MBLS主要发生在MTBI患者的脑皮层中;MRSWI能为MTBI患者的诊断提供影像学上的证据。     

Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non‐TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter‐specific registration followed by whole‐brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with “feeling dazed or confused,” but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast‐ and impact‐related mild TBI that involves a cascade of inflammatory and neurochemical events. Hum Brain Mapp 34:2986–2999, 2013. © 2012 Wiley Periodicals, Inc.     

重型颅脑损伤血清Caspase-3的水平变化及其意义

目的 探讨重型颅脑损伤（TBI）病人入院血清天冬氨酸半胱氨酸特异性蛋白酶-3 （Caspase-3）水平变化及临床意义。方法 选取2016年6月~2019年6月收治的重型TBI病人120例,另选取性别、年龄相匹配的健康体检者120例为对照。根据伤后30 d内存活情况将TBI病人分为存活组（n=91）和死亡组（n=29）。采用酶联免疫吸附试验法检测入院血清Caspase-3水平。结果 重型TBI组血清Caspase-3水平明显高于对照组（P<0.05）。死亡组血清Caspase-3水平明显高于存活组（P<0.05）。重型TBI病人入院血清Caspase-3浓度与入院GCS评分呈负相关,与入院Marshall CT分级和血清C-反应蛋白（CRP）呈正关（P<0.05）。多因素logistic回归分析显示入院GCS评分3~5分、入院Marshall CT分级Ⅴ~Ⅵ级、入院血清CRP >20 mg/L、入院血清Caspase-3>548 ng/ml是重型TBI病人伤后30d内死亡的独立危险因素（P<0.05）。ROC曲线分析结果显示入院血清Caspase-3预测重型TBI病人伤后30 d内死亡的最佳临界值为423 ng/ml,曲线下面积为0.862,灵敏度为85.69%、特异度为64.50%。结论 重型TBI病人入院血清Caspase-3水平显著升高,对预测病人伤后30 d内死亡有一定价值。     

人性化手术室护理对轻度脑外伤手术患者焦虑与抑郁情绪的影响

目的探讨人性化手术室护理对轻度脑外伤手术患者焦虑、抑郁情绪的影响。方法临床纳入轻度脑外伤手术患者70例,根据围手术期护理方案分为研究组与对照组。研究组实施人性化手术室护理,对照组实施常规护理。采用焦虑自评量表(self-rating anxiety scale,SAS)、抑郁自评量表(self-rating depression scale,SDS)、自尊量表(self-esteem scale,SES)评定2组干预前后的心理状况,对比2组患者及家属对护理的满意度。结果 2组干预前SAS、SDS、SES评分差异均无统计学意义(P0.05)。干预后研究组SAS、SDS、SES评分分别为36.27±3.89、32.47±2.94、43.96±3.83,对照组分别为41.98±3.96、39.12±3.55、38.22±3.01,差异均有统计学意义(P0.05);研究组患者及家属对护理满意度97.14%,对照组为71.43%,差异有统计学意义(P0.05)。结论围手术期对轻度脑外伤手术患者进行人性化手术室护理,能够显著降低术前患者的焦虑、抑郁等不良情绪,且可以提高患者及家属对护理工作的满意度。     

A fixel‐based analysis of micro‐ and macro‐structural changes to white matter following adult traumatic brain injury

Diffusion tensor imaging is often used to assess white matter (WM) changes following traumatic brain injury (TBI), but is limited in voxels that contain multiple fibre tracts. Fixel‐based analysis (FBA) addresses this limitation by using a novel method of analysing high angular resolution diffusion‐weighted imaging (HARDI) data. FBA examines three aspects of each fibre tract within a voxel: tissue micro‐structure (fibre density [FD]), tissue macro‐structure (fibre‐bundle cross section [FC]) and a combined measure of both (FD and fibre‐bundle cross section [FDC]). This study used FBA to identify the location and extent of micro‐ and macro‐structural changes in WM following TBI. A large TBI sample (N_mild = 133, N_{moderate–severe} = 29) and control group (healthy and orthopaedic; N = 107) underwent magnetic resonance imaging with HARDI and completed reaction time tasks approximately 7 months after their injury (range: 98–338 days). The TBI group showed micro‐structural differences (lower FD) in the corpus callosum and forceps minor, compared to controls. Subgroup analyses revealed that the mild TBI group did not differ from controls on any fixel metric, but the moderate to severe TBI group had significantly lower FD, FC and FDC in multiple WM tracts, including the corpus callosum, cerebral peduncle, internal and external capsule. The moderate to severe TBI group also had significantly slower reaction times than controls, but the mild TBI group did not. Reaction time was not related to fixel findings. Thus, the WM damage caused by moderate to severe TBI manifested as fewer axons and a reduction in the cross‐sectional area of key WM tracts.     

Temporal and egional profiles of cytoskeletal protein accumulation in the rat brain following traumatic brain injury

Abstract To characterize the cytoskeletal aberration due to traumatic injury, temporal and regional profiles of changes in immunoreactivity of microtubule-associated protein 2 (MAP2), neurofilament heavy subunit protein (NFH) and heat shock protein 72 (HSP72) were investigated after different magnitudes of traumatic brain injury by fluid percussion. The experimental rat brain was perfusion-fixed at 1, 6 and 24 hours after traumatic brain injury. Conventional histological staining has demonstrated that the mildest traumatic brain injury (1.0 atm) induced no neuronal loss at the impact site and that neuron loss was apparent when traumatic brain injury was increased to 4.3 atm. The mildest traumatic brain injury, however, caused a significant increase in HSP72 immunoreactivity in the superficial cortical layers at the impact site as early as 1 hour after the injury. In the case of severe traumatic brain injury (4.3 atm), neuron loss was apparent in the area at the impact site, but the increase in HSP72 immunoreactivity was moderate, and it was observed only after 6 hours in the deep cortical layers under the necrotic area. The increased immunostaining of MAP2 was demonstrated in damaged axons and neuronal perikarya in the wider area surrounding the impact site at 6 and 24 hours after the injury. Six and 24 hours after the injury, perikaryal accumulation of neurofilament was observed, and the accumulated neurofilament was mostly phosphorylated. These results indicate that the severe traumatic brain injury of 4.3 atm triggers the abnormal accumulation of cytoskeletal proteins in neuronal perikarya, most probably due to an impairment of axonal transport. It is implied that the increased expression of HSP72 may be involved in the protective process of neurons after traumatic brain injury.     

Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury

Infants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs). OPCs, in turn, develop into premyelinating OLs and finally mature into myelinating OLs. Recent studies revealed that OPCs develop in multiple waves and form potentially heterogeneous populations. Furthermore, it has been shown that myelination is a dynamic and plastic process with an excess of OPCs being generated and then abolished if not integrated into neural circuits. Myelination patterns between rodents and humans show high spatial and temporal similarity. Therefore, experimental studies on OL biology may provide novel insights into the pathophysiology of WMI in the preterm infant and offers new perspectives on potential treatments for these patients.     

Diagnostic terminology,athlete status,and history of concussion affect return to play expectations and anticipated symptoms following mild traumatic brain injury

“Mild traumatic brain injury” (mTBI) and “concussion” are terms often used interchangeably. However, “mTBI” is frequently seen as representing a broader injury that encompasses the construct of “concussion,” which often conveys transience or decreased severity. The present study examined the influence of varying diagnostic terminology on acute injury expectations in an undergraduate population (N = 105). Participants were presented with an mTBI vignette and were randomly assigned to one of two conditions in which the term “mTBI” or “concussion” was used to describe the injury. There were no significant differences between the two conditions on anxiety, symptomatology, timeline, or consequence scales. However, participants in the “mTBI” group allocated more days to return to play than participants in the “concussion” group, suggesting that terminology has an effect on perceptions of the severity of the injury. Varsity athletes allocated fewer days to return to play than nonathletes. Individuals with a history of concussion, both athletes and nonathletes, indicated fewer days to return to play, but greater symptomatology than individuals with no history of concussion. Clinicians should consider the influence of diagnostic terminology, athletic background, and history of concussion on perceptions of the severity of an injury because expectations can influence injury outcomes and compliance in a recovery process.     

Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus

The molecular events responsible for impairments in cognition following mild traumatic brain injury are poorly understood. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), have been identified as having a role in learning and memory. We have previously demonstrated that following experimental brain trauma of moderate severity (2.0-2.1 atm), mRNA levels of BDNF and its high-affinity receptor, trkB, are increased bilaterally in the hippocampus for several hours, whereas NT-3 mRNA expression is decreased. In the present study, we used in situ hybridization to compare BDNF, trkB, NT-3, and trkC mRNA expression in rat hippocampus at 3 or 6 h after a lateral fluid percussion brain injury (FPI) of mild severity (1.0 atm) to sham-injured controls at equivalent time points. Mild FPI induced significant increases in hybridization levels for BDNF and trkB mRNAs, and a decrease in NT-3 mRNA in the hippocampus. However, in contrast to the bilateral effects of moderate experimental brain injury, the present changes with mild injury were restricted to the injured side. These findings demonstrate that even a mild traumatic brain injury differentially alters neurotrophin and neurotrophin receptor levels in the hippocampus. Such alterations may have important implications for neural plasticity and recovery of function in people who sustain a mild head injury.