Comparison of labeling methods and time course of traumatic brain injury-induced cell death in mice

BACKGROUND:Various molecular mechanisms of cell death following traumatic brain injury have been previously described.However,the time course of cell death remains unclear.TUNEL and Fluoro-Jade B labeling have been widely used to label apoptotic cells and neuronal degeneration.Propidium iodide (PI) functions as a biomarker of cell death in vivo.OBJECTIVE:To explore the role of PI labeling compared to TUNEL and Fluoro-Jade B staining for detecting neural cell death,and to observe time course of traumatic brain injury-induced cell death in mice.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Laboratory of Aging and Nervous Diseases,Soochow University from September 2007 to December 2008.MATERIALS:PI (B1221) was purchased from Sigma,USA.TUNEL kit was purchased from Roche Molecular Biochemicals,USA.Fluoro-Jade B was purchased from Chemicon,USA.METHODS:A total of 70 healthy,male,Kunming mice were randomly assigned to sham-surgery (n = 5) and model (n = 65) groups.Traumatic brain injury was established using the controlled cortical impact method.PI was intraperitoneally injected at 1 hour prior to animal sacrifice.MAIN OUTCOME MEASURES:TUNEL,Fluoro-Jade B,and Pl-positive cells were quantified using a double-labeling method to determine the time course of traumatic brain injury-induced cell death.RESULTS:PI labeled cells in an earlier phase of cell death than TUNEL and Fluoro-Jade B labeling.Pl-positive cells were observed immediately following injury,and the numbers rapidly increased in injured brain areas at 1 hour,peaked at 24-48 hours,and subsequently decreased at 3-21 days post-injury.TUNEL-labeled cells were significantly increased at 12 hours,while Fluoro-Jade B-labeled cells were increased at 6 hours after injury,with cells still visible at 6-48 hours post-injury.Moreover,a greater number of Pl-positive cells were observed compared to TUNEL- and Fluoro-Jade B-labeled cells.CONCLUSION:PI labeling is more sensitive and reliable than TUNEL and Fluoro-Jade B staining for detecting cell death following traumatic brain injury.Moreover,PI labeling can function as a reliable marker to estimate the entire time course of cell death.     

颅脑外伤后脑梗死危险因素分析

目的分析探讨颅脑外伤后脑梗死的发生机制以及危险因素。方法采用回顾性研究方法,调查110例颅脑外伤病例,分析颅脑外伤后脑梗死的相关因素。结果颅脑损伤后并发脑梗死与GCS评分、年龄、有无蛛网膜下腔出血、有无脑疝、是否有高血压病史有关,差异有统计学意义(P<0.05),与患者性别、受伤原因以及类型无关,差异无统计学意义(P>0.05)。结论中、重型颅脑外伤患者有脑疝、蛛网膜下腔出血及高龄、合并高血压病史易发生外伤性脑梗死。对脑外伤的及早综合治疗,积极预防脑梗有助于改善患者预后,降低致残及死亡率,提高患者的生存质量。     

Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury

OBJECTIVE: Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission. PATIENTS AND METHODS: Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study. RESULTS: Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization. CONCLUSION: There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate, there was 26% fall (P = 0.05) only in ICU length of stay.     

Sequential expression of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor in rat hippocampal neurons after fluid percussion injury

Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott’s method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury.     

Endogenous adult neurogenesis and cognitive function recovery following traumatic brain injury in the rat hippocampus

BACKGROUND:Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE:To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS:Mouse anti-rat 5-bromodeoxyuridine (BrdU) and neuronal nuclei (NeuN) monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS:A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to (182 ± 2) kPa and (284 ± 4) kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES:Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS:At 7 days post-injury,the number of BrdU+ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group (P<0.01).At 61 days post-injury,the number of BrdU7NeuN+ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups (P< 0.01).In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups (P< 0.01).Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits (P< 0.01).CONCLUSION:Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.     

Implications of Psychometric Measurement for Neuropsychological Interpretation

The present study sought to determine whether cognitive outcome and course of recovery in civilian penetrating brain injury due to gunshot can be distinguished from that of non-penetrating brain injury due to motor vehicle accident. Matched survivors of penetrating and non-penetrating brain injury were assessed with a brief neuropsychological test battery at inpatient rehabilitation, 1 year post-injury, and 2 years post-injury. The traumatic brain injury groups were found to have patterns of performance marked by reliably distinct differences in isolated areas, with different cognitive predictors of brain injury type present in early versus later recovery. The degree of recovery over the first 2 years appeared to be quite similar for penetrating and non-penetrating injuries.      

Early and late outcome in head injury patients with radiological evidence of brain damage

This study examined the early and late outcome in head injury patients with focal or multifocal (unilateral or bilateral) brain contusions revealed by computerized tomography (CT) scanning. The outcome was also evaluated in patients hospitalized due to brain concussion. Three months after the injury (the early outcome) 43% of the 86 cases with multifocal contusions on the CT scan were dead. As evaluated by the Glasgow Outcome Scale, all the 57 patients with a focal brain contusion, as well as the 117 cases with brain concussion, made a good recovery or were moderately disabled. The late outcome (1 to 5 years after injury) was evaluated in 78 cases with brain contusion and in 85 cases with brain concussion, and revealed that complaints and impaired adaptive functioning were frequent in both the contusion and concussion group. The occurrence of headache, dizziness and sleep problems did not significantly differ among the various head injury groups. However, focal or multifocal brain contusions on the CT scan increased the frequency of impaired memory, impaired concentration, speech problems, weakness in arms or legs and seizures with loss of consciousness. Cognitive deficits and speech problems were particularly common in patients with a focal contusion in the temporal lobe. The late adaptive and social functioning were most markedly impaired in cases with multifocal bilateral contusions.     

Patterns of Increased Intracranial Pressure After Severe Traumatic Brain Injury

Introduction  Secondary brain injury due to increased intracranial pressure (ICP) contributes to post-traumatic morbidity and mortality. Although it is often taught that increased ICP begins early after traumatic brain injury, some patients develop increased ICP after the first 3 days post-injury. We examined our data to describe temporal patterns of increased ICP. Methods  This is a retrospective review of prospectively collected physiologic and demographic data. Results  Seventy-seven patients were included. We identified four patterns of increased ICP: beginning within 72 h (early), beginning after 72 h (late), early increases with resolution, and then a second rise after 72 h (bimodal), and continuously increased ICP. Late increases in ICP occur in 17% of this cohort. Peak day of swelling was day 7 for the “late” rise group and day 4 for the other patients with increased ICP. Forty-four percent of patients showed enlargement of cerebral contusions on follow-up imaging at 24 h post-injury. Conclusions  Late rises in ICP were not rare in this cohort. This is clinically relevant as it may impact decisions about ICP monitor removal. Differences between groups in age, CT patterns of injury, fluid therapy, osmotic use, and fever were not statistically significant. Portions of this work were presented in poster form at the 5th Annual Neurocritical Care Society Meeting in Las Vegas, NV, on November 2, 2007.     

Microstructural basis of contusion expansion in traumatic brain injury: insights from diffusion tensor imaging

Traumatic brain injury (TBI) is often exacerbated by events that lead to secondary brain injury, and represent potentially modifiable causes of mortality and morbidity. Diffusion tensor imaging was used to characterize tissue at-risk in a group of 35 patients scanned at a median of 50 hours after injury. Injury progression was assessed in a subset of 16 patients with two scans. All contusions within the first few days of injury showed a core of restricted diffusion, surrounded by an area of raised apparent diffusion coefficient (ADC). In addition to these two well-defined regions, a thinner rim of reduced ADC was observed surrounding the region of increased ADC in 91% of patients scanned within the first 3 days after injury. In patients who underwent serial imaging, the rim of ADC hypointensity was subsumed into the high ADC region as the contusion enlarged. Overall contusion enlargement tended to be more frequent with early lesions, but its extent was unrelated to the time of initial imaging, initial contusion size, or the presence of hemostatic abnormalities. This rim of hypointensity may characterize a region of microvascular failure resulting in cytotoxic edema, and may represent a ‘traumatic penumbra'' which may be rescued by effective therapy.     

Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study

OBJECTIVE: Patients who had suffered traumatic brain injury were evaluated to determine the occurrence of psychiatric disorders during a 30-year follow-up. METHOD: Sixty patients were assessed on average 30 years after traumatic brain injury. DSM-IV axis I disorders were diagnosed on a clinical basis with the aid of the Schedules for Clinical Assessment in Neuropsychiatry (version 2.1), and axis II disorders were diagnosed with the Structured Clinical Interview for DSM-III-R Personality Disorders. Cognitive impairment was measured with a neuropsychological test battery and the Mini-Mental State Examination. RESULTS: Of the 60 patients, 29 (48.3%) had had an axis I disorder that began after traumatic brain injury, and 37 (61.7%) had had an axis I disorder during their lifetimes. The most common novel disorders after traumatic brain injury were major depression (26.7%), alcohol abuse or dependence (11.7%), panic disorder (8.3%), specific phobia (8.3%), and psychotic disorders (6.7%). Fourteen patients (23.3%) had at least one personality disorder. The most prevalent individual disorders were avoidant (15.0%), paranoid (8.3%), and schizoid (6.7%) personality disorders. Nine patients (15.0%) had DSM-III-R organic personality syndrome. CONCLUSIONS: The results suggest that traumatic brain injury may cause decades-lasting vulnerability to psychiatric illness in some individuals. Traumatic brain injury seems to make patients particularly susceptible to depressive episodes, delusional disorder, and personality disturbances. The high rate of psychiatric disorders found in this study emphasizes the importance of psychiatric follow-up after traumatic brain injury.     

外伤性胼胝体损伤的MRI诊断

[目的] 观察颅脑创伤致胼胝体损伤的MRI表现,为临床提供有价值的诊断信息,提高颅脑创伤的救治水平. 方法 回顾分析临沂市人民医院神经外科自2007年至2009年收治疗的20例MRI证实为胼胝体损伤患者的临床、影像资料,观察其临床表现及MRI各序列特征. 结果 外伤性胼胝体损伤在临床较为少见,以非出血性损伤为主,损伤部位常见于体部及压部,少数位于膝部,嘴部损伤罕见.对于早期非出血性损伤,MRI常表现为稍长T1稍长T2信号,且常伴弥漫性轴索损伤的表现.在胼胝体损伤的中后期,胼胝体局部往往萎缩,病灶区易出现液化坏死,可有胶质瘢痕及软化灶形成,在MR/表现为长T1长T2信号,且信号强度近似于脑脊液,还可见相应部位的脑室扩大.在弥散加权成像(DWI)可见非出血性损伤在急性期和亚急性期呈高信号,随着时间延长,信号逐渐减低至正常脑组织信号,如形成软化灶,则表现为脑脊液信号. 结论 外伤性胼胝体损伤可引起严重后果,在重型颅脑损伤中并不罕见,应当引起临床医生重视.MRI是显示胼胝体损伤病灶最好的影像学检查手段,不仅对其微小病变敏感显示,且能够多方位地显示病变.     

颅脑创伤后凝血功能障碍的研究进展

颅脑创伤作为一种常见的创伤类型,给社会以及家庭造成了沉重的负担。凝血功能障碍在颅脑创伤后十分常见,尤其多见于服用了抗凝或抗血小板聚集药物的患者。颅脑创伤后凝血功能障碍的发生机制复杂,并且没有统一的诊断标准,但是其出现往往导致进展性颅内出血的发生,严重影响患者预后。成分输血以及相关血液制品和止血药物的应用是目前纠正颅脑创伤后凝血功能障碍的主要治疗手段。本文将对颅脑创伤后凝血功能障碍的发生机制、诊断和治疗的研究现状做一综述。     

Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies

It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury.     

Neural correlates of self-evaluative accuracy after traumatic brain injury

Individuals who have sustained a traumatic brain injury (TBI) often exhibit an array of cognitive deficits, yet perhaps most maladaptive of these sequelae is the frequent occurrence of reduced insight into one's own condition. In such cases, TBI individuals may overestimate their post-injury level of socio-cognitive functioning, leading to disparities between how they perceive themselves and what others observe. This functional MRI (fMRI) investigation examined the relationship between level of insight into one's post-injury condition (i.e. trait/ability status) and neural activation evoked during an fMRI task involving self-appraisal of one's traits and abilities. Twenty TBI patients (8-12 weeks post-injury, ER Glasgow Coma Scale Average = 10.9+/-2.8) were selected on the criterion that they overestimate their current trait/abilities (as detected on the patient competency rating scale, PCRS). fMRI activation on the self-appraisal task was compared between the TBI patients and 20 matched controls. For both groups, the fMRI task evoked activation at mid-line prefrontal and retrosplenial cortices. TBI patients exhibited greater signal change in the anterior cingulate, precuneus and right temporal pole. Subsequently, a linear regression analysis was conducted for the TBI group, with the PCRS and a measure of cognitive speed entered as predictor variables to determine the selective effect of insight on self-evaluative brain activation. A more accurate level of trait/ability-based insight was related to increased signal change in the right anterior dorsal prefrontal cortex (PFC). The results suggest that one's post-injury level of self-referential insight is related to a network inclusive of the medial and right dorsal PFC.     

外伤后颅内进展性出血性损伤106例分析

目的探讨颅脑损伤后进展性出血性损伤（PHI）的发生及影响预后的相关因素。方法对2007年颅脑损伤后出现PHI的106例患者的临床资料进行回顾性分析,并与同期无PHI患者进行对照研究。结果颅脑损伤后是否出现PHI与患者的年龄是否超过50岁（P〈0．05）、血浆纤维蛋白原水平是否低于2g／L（P〈0．01）及有无蛛网膜下腔出血（SAH）（P〈0．05）密切相关。PHI患者的预后与年龄是否超过50岁（P〈0．01）、血浆纤维蛋白原水平是否低于2g／L（P〈0．01）、有无SAH（P〈0．01）及入院时的GCS评分（P〈0．01）密切相关。结论PHI最常出现于颅脑伤后12h内,好发于着力点的对冲部位,以额颞部为主,与患者的年龄、血浆纤维蛋白原水平及是否伴有SAH等因素密切相关;其预后与患者的年龄是否超过50岁、入院时GCS评分、血浆纤维蛋白原水平是否低于正常及是否伴有SAH密切相关。     

Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury

Stem/progenitor cells reside throughout the adult CNS and are actively dividing in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. This neurogenic capacity of the SVZ and DG is enhanced following traumatic brain injury (TBI) suggesting that the adult brain has the inherent potential to restore populations lost to injury. This raises the possibility of developing strategies aimed at harnessing the neurogenic capacity of these regions to repair the damaged brain. One strategy is to enhance neurogenesis with mitogenic factors. As basic fibroblast growth factor (bFGF) is a potent stem cell mitogen, we set out to determine if an intraventricular administration of bFGF following TBI could affect the levels of injury-induced neurogenesis in the SVZ and DG, and the degree to which this is associated with cognitive recovery. Specifically, adult rats received a bFGF intraventricular infusion for 7 days immediately following TBI. BrdU was administered to animals daily at 2-7 days post-injury to label cell proliferation. At 1 or 4 weeks post-injury, brain sections were immunostained for BrdU and neuronal or astrocytic markers. We found that injured animals infused with bFGF exhibited significantly enhanced cell proliferation in the SVZ and the DG at 1 week post-TBI as compared to vehicle-infused animals. Moreover, following bFGF infusion, a greater number of the newly generated cells survived to 4 weeks post-injury, with the majority being neurons. Additionally, animals infused with bFGF showed significant cognitive improvement. Collectively, the current findings suggest that bFGF-enhanced neurogenesis contributes to cognitive recovery following TBI.     

Deleterious poly(ADP-ribose)polymerase-1 pathway activation in traumatic brain injury in rat

Traumatic brain injury produces nitric oxide and reactive oxygen species. Peroxynitrite, resulting from the combination of nitric oxide and superoxide anions, triggers DNA strand breaks, leading to the activation of poly(ADP-ribose)polymerase-1. As excessive activation of this enzyme induces cell death, we examined the production of nitrosative stress, the activation of poly(ADP-ribose)polymerase-1, and the role of this enzyme in the outcomes of traumatic brain injury produced by fluid percussion in rats. Immunohistochemistry showed that 3-nitrotyrosine, an indicator of nitrosative stress, and poly(ADP-ribose), a marker of poly(ADP-ribose)polymerase-1 activation, were present as early as 30 min post-injury, and that persisted for 72 h. The poly(ADP-ribose)polymerase inhibitor, 3-aminobenzamide, at 10 and 30 mg/kg, significantly improved the neurological deficit, with a 60% reduction in the brain lesion volume and inhibition of poly(ADP-ribose)polymerase-1 activation. Thus, poly(ADP-ribose)polymerase-1 is involved in the neurological consequences of traumatic brain injury and may be a promising therapeutic target in clinical treatment of acute brain trauma.     

颅脑外伤对患者智能状况的影响及相关因素研究

目的：研究颅脑外伤对患者智能状况的影响，探讨与之相关的生物、心理、社会因素。方法：本研究对63例急性期颅脑外伤患者，采用标准化测评工具，包括《格拉斯哥昏迷评分（GCS）》、《简易智力状态检查》、《数字划消测验》、《社会支持评定量表》、《日常生活能力量表》及自制颅脑外伤患者人口学与相关因素调查表等，逐例进行现场临床测评，将拟分析的因素进行量化，最后将汇总的资料进行整理，分析、总结。所有统计分析均使用SAS软件包完成。结果：颅脑外伤患者智能缺陷的发生率为71．43％，其显著性差异表现在文化程度、治疗措施及手术类型三个方面，主要影响因素有外伤程度、外伤部位、社会支持、文化程度及治疗措施。结论：不同外伤类型的颅脑外伤对患者的智能状 况产生不同程度的影响，其相关因素包括生物、心理、社会学三个方面，基础的生物学病因虽然对智能起决定作用，而社会心理因素的影响仍不可忽视。     

Persistent alterations in cerebrovascular reactivity in response to hypercapnia following pediatric mild traumatic brain injury

Much attention has been paid to the effects of mild traumatic brain injury (mTBI) on cerebrovascular reactivity in adult populations, yet it remains understudied in pediatric injury. In this study, 30 adolescents (12–18 years old) with pediatric mTBI (pmTBI) and 35 age- and sex-matched healthy controls (HC) underwent clinical and neuroimaging assessments during sub-acute (6.9 ± 2.2 days) and early chronic (120.4 ± 11.7 days) phases of injury. Relative to controls, pmTBI reported greater initial post-concussion symptoms, headache, pain, and anxiety, resolving by four months post-injury. Patients reported increased sleep issues and exhibited deficits in processing speed and attention across both visits. In grey-white matter interface areas throughout the brain, pmTBI displayed increased maximal fit/amplitude of a time-shifted end-tidal CO₂ regressor to blood oxygen-level dependent response relative to HC, as well as increased latency to maximal fit. The alterations persisted through the early chronic phase of injury, with maximal fit being associated with complaints of ongoing sleep disturbances during post hoc analyses but not cognitive measures of processing speed or attention. Collectively, these findings suggest that deficits in the speed and degree of cerebrovascular reactivity may persist longer than current conceptualizations about clinical recovery within 30 days.     

Expression of nitric oxide synthase in the cerebral microvasculature after traumatic brain injury in the rat

Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) histochemistry and nitric oxide synthase (NOS) immunocytochemistry were performed on sections of brain after moderate traumatic brain injury. There was a pronounced increase in NADPHd reactivity and an induction of the endothelial NOS (eNOS) isoform in microvessels surrounding the cortical contusion by 24 h post-injury. This altered microvascular state may contribute to barrier breakdown and hyperemia which characterize traumatic brain injury.