Protective effect of erythropoietin on type II pneumocyte cells after traumatic brain injury in rats

BACKGROUND: The main objective was to evaluate the protective effect of erythropoietin on lung ultrastructure against damage in rats after traumatic brain injury. METHODS: We used forty Wistar-Albino female rats weighing 170-200 gr. The rats were allocated into five groups. The first group was the control and the second was the craniotomy without trauma. The third group was the trauma group. The fourth and fifth groups were erythropoietin (1000 IU/kg) and vehicle (0.4 mL/rat) groups, respectively. A weight-drop method was used for achieving head trauma. Samples were obtained from pulmonary lobes 24-hour post injury. Lipid peroxidation levels were determined and electron microscopic scoring model was used to reveal the ultrastructural changes. RESULTS: Ultrastructural evaluation revealed pathologic changes in the trauma group compared with the control group (p < 0.05). Lipid peroxidation levels were found to be higher in the trauma group (p < 0.05). Erythropoietin significantly reduced both the ultrastructural pathologic changes and the lipid peroxidation levels in the treatment group (p < 0.05). CONCLUSIONS: Erythropoietin protects the ultrastructure of pneumocyte type II cells against damage after traumatic brain injury.     

Ultrastructural changes in tracheobronchial epithelia following experimental traumatic brain injury in rats: Protective effect of erythropoietin

BACKGROUND: We aimed to demonstrate the time dependent ultrastructural changes in tracheobronchial epithelia after traumatic brain injury. And also, protective effect of erythropoietin was demonstrated. METHODS: We used 56 Wistar-Albino female rats weighing 170 to 200 g. The rats were allocated into 7 groups. First group was the control. The second underwent craniotomy without trauma. The third, fourth, and fifth groups were respectively 2-, 8-, and 24-hour trauma groups. The sixth and seventh groups were respectively treatment (erythropoietin, 1,000 IU/kg) and vehicle (0, 4 ml/rat) groups. Weight-drop method was used for achieving head trauma. Samples were obtained from both trachea and main bronchi. Modified electron microscopic scoring model was used to reveal the ultrastructural changes in both trauma and treatment groups. RESULTS: There was no statistical difference between control and sham groups (p >0.05). Scores of all trauma groups were significantly different from the controls (p <0.05). Trauma produced obvious gradual damage on ultrastructure of the tracheobronchial epithelia. Erythropoietin decreased tracheobronchial scores after traumatic brain injury in significant levels. Erythropoietin attenuated ultrastructural scores for each organelle in significant levels (p <0.05 for each organelle). CONCLUSIONS: The data suggested that ultrastructural damage is obvious at 2 hours deteriorating with time. Erythropoietin protects epithelia against damage after traumatic brain injury. Pharmaceutical lung preservation may help gaining efficacious donor lungs in brain death. But, further time dependent experiments are needed to determine the liability of the donor lung after traumatic brain injury. This fact is to be known for achieving higher graft survival rates.     

Mitochondrial metabolism following traumatic brain injury in rats

Although a number of studies of traumatic brain injury have implicated mitochondrial dysfunction as a cause of altered posttraumatic energy metabolism, no studies to date have isolated mitochondria and measured their respiratory capacity following trauma. The present study sought to determine whether mitochondrial capacity for oxidative phosphorylation is adversely affected by fluid-percussion-induced traumatic brain injury in rats. Prior to brain injury, the mitochondrial respiratory control ratio was 4.3 +/- 0.2 and the ratio of nmoles of ADP phosphorylated per natom oxygen consumed (ADP/O ratio) was 2.66 +/- 0.09. After injury (2.8 atm; t = 4 h), there were slight but not significant alterations in ADP/O ratio (2.41 +/- 0.07) and state 3 respiratory rate (ADP stimulated); however, there were no changes in the respiratory control ratio. These data suggest that traumatic brain injury, unlike ischemia, does not cause uncoupling of ATP synthesis from respiration, and that brain mitochondria are quite resistant to trauma-induced injury.     

Local mitochondrial function following traumatic brain injury in rats

The effect of lateral fluid percussion injury on mitochondrial function in the rat brain was investigated by quantitative imaging of changes in the regional activity of succinate dehydrogenase (SDH), a mitochondrial enzyme of the tricarboxylic acid cycle for adenosine triphosphate production. Regional SDH was measured in the frontal, parietal, temporal, and occipital cortices, CA1 and CA2-3 of the hippocampus, thalamus, corpus callosum, caudate/putamen, and cerebellum 1 hour and 72 hours after low, medium, and high pressure injury. No regional difference between the hemispheres in the activity of SDH was observed in the sham group. The hippocampus showed high SDH activity. The CA2-3 regions showed the highest activity among the regions examined. The corpus callosum, which is white matter, showed the lowest. One hour after low pressure fluid percussion injury, only the frontal lobe showed significantly lower SDH activity than the sham control in the ipsilateral hemisphere, whereas after 72 hours SDH activity was significantly lower in the frontal, parietal, and temporal lobes. SDH activity was significantly lower in the frontal, parietal, and temporal lobes in the medium and high pressure injury groups than in the sham control 1 hour after injury, and SDH activity in the CA1 and CA2-3 of the hippocampus was significantly decreased 72 hours after injury. No decrease in SDH activity was observed in any region of the contralateral hemisphere either 1 hour or 72 hours after injury. Mitochondrial dysfunction of the ipsilateral cortex and hippocampus following fluid percussion injury is correlated with the severity of injury and advances with time after injury. The results suggest that progression of mitochondrial dysfunction is associated with secondary bioenergetic deterioration.     

Kinematic changes following botulinum toxin injection after traumatic brain injury

The objectives of this study were to: (1) demonstrate the use of computerized, three-dimensional gait analysis as a functional assessment instrument following clinical intervention and (2) objectively quantify the effects of focal muscle denervation via botulinum toxin type A (BTXA) injection in a hemiparetic patient with lower extremity spasticity following traumatic brain injury (TBI). A desired outcome of this intervention was to realize kinematics more closely resembling those reported for normal patients. The design was a single-subject case study. Ten trials of walking gait were analysed pre-injection (PI), 1 week post-injection (1PO) and 4 weeks post-injection (4PO). The PI and 1PO sessions were found to be appreciably different from the 4PO on the joint angles of the ankle and knee at each phase of the gait cycle. These differences resulted in a reduced asymmetry of ambulation. Stride time, stance time, percentage stance time, percentage swing time and walking speed improved, showing progress towards a more efficient gait pattern. Decreased stride time and increased walking speed supported improved functional ability. The inter-trial variability of the gait parameters showed the analysis to be a consistently reproducible protocol. Conclusions based on the results included encouraging findings for the efficacy of botulinum toxin A as a therapy for the reduction of spasticity.     

Lubeluzole following traumatic brain injury in the rat.

Lubeluzole, a novel nitric oxide synthase (NOS) pathway modulator, was shown to be neuroprotective in cerebral ischemia as studied in animal models and clinical trials. The present study investigated the effect of lubeluzole on contusion volume and brain edema following traumatic brain injury. Sprague-Dawley rats (n = 36) were subjected to cortical impact injury. Lubeluzole (0.8 mg/kg i.v.; n = 18) or a corresponding volume of vehicle (n = 18) was injected 15 and 75 minutes following trauma. Animals were sacrificed 24 hours following trauma. Contusion volume was measured planimetrically from coronal slices stained with hematoxylin and eosin. In this group, T2-weighted magnetic resonance imaging (MRI) was also performed 90 minutes and 6 and 24 hours after trauma. Hemispheric swelling and water content were determined gravimetrically 24 hours after trauma. In this group, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were monitored for 30 minutes before sacrifice. Lubeluzole did not reduce contusion volume, hemispheric swelling, or water content. ICP, MABP, and the resulting CPP did not differ between treated and untreated rats 24 hours after injury. T2-weighted MRI revealed a higher volume of edema at 90 minutes after trauma in treated rats. However, at 6 and 24 hours after trauma, no significant difference was discernible. Under these experimental conditions, lubeluzole fails to exert beneficial effects following experimental traumatic brain injury (TBI).     

Psychiatric comorbidity following traumatic brain injury

Primary objective: Survivors of traumatic brain injury (TBI) are at increased risk for development of severe, long-term psychiatric disorders. However, the aetiology of these disorders remains unclear. This article systematically reviews the most current prevalence rates and evidence for causality, in terms of established criteria.

Main outcome and results: Psychiatric syndromes are consistently present at an elevated rate following TBI. Survivors of TBI are particularly susceptible to major depression, generalized anxiety disorder and post-traumatic stress disorder. Evidence for a biological gradient is generally lacking, although this criterion may not be appropriate in the case of TBI. The temporal pattern of onset is variable and reliable critical periods for the post-injury development of a psychiatric disorder remain to be identified; however, individuals appear to remain at risk for years following injury.

Conclusions: Non-organic factors, including pre-morbid personality traits and post-injury psychological reactions to disability and trauma, are implicated in the generation and maintenance of post-TBI psychiatric disorder. There remains insufficient evidence to conclude what role the neuropathological consequences of TBI play in the development of post-TBI psychiatric disorder.     

Service utilization following traumatic brain injury

OBJECTIVES: To document service utilization by people with a traumatic brain injury at different times postinjury and to identify factors that predict service use. DESIGN: Cross-sectional study design. Four groups of subjects were randomly selected from a regional database, according to their time postinjury: 6-18 months; 2-4 years; 6-9 years; and 10-17 years. SUBJECTS: A total of 119 adults with a traumatic brain injury (TBI). SETTING: Hospital and community-based clients in Sydney, Australia. OUTCOME MEASURES: Glasgow Outcome Scale, Disability Rating Scale; Functional Independence Measure; Lidcombe Psychosocial Disability Scale; number, type, and frequency of services used in the previous 12 months. RESULTS: Subjects in all four groups used a variety of services. The mean number of services used was 4.2, and there was only a moderate decline in service use over time. The use of medical and allied health services remained high in all four groups. Severity of injury, physical and cognitive disability, and psychosocial disability were all predictors of service utilization. Psychosocial disability was strongly associated with ongoing service utilization. CONCLUSION: In this study, people with TBI used services well beyond the early stage of recovery. Psychosocial disability may be a better predictor of service use than physical and cognitive disability alone.     

Sleep disturbances following traumatic brain injury

Opinion statement  

The effect of age on outcome following traumatic brain injury in rats

Age of the patient is one of the most important predictors of outcome following human traumatic brain injury. This study employs the fluid-percussion model to investigate the effects of aging on outcome following traumatic brain injury in rats. The results revealed that there was an age-associated increase in mortality rate following both low (1.7 to 1.8 atm) and moderate (2.00 to 2.25 atm) levels of traumatic brain injury. Age-related changes in systemic physiological, neurological, and histopathological indexes of brain injury were also examined following a low level of traumatic brain injury. Traumatic brain injury produced equivalent acute hypertension and increased plasma glucose levels in both young adult and aging rats. Injury produced an acute increase in heart rate in the young adult rat group, while the heart rate decreased in the aged rats. At low levels of brain injury, no significant gross histopathological alterations were produced in either age group. Neurological outcome was assessed by measuring the duration of suppression of a number of nonpostural and postural reflexes and more complex somatomotor functions (righting, escape, head support). Except for head support, there was a significant age-related increase in the duration of the suppression of these reflexes following brain injury. These data demonstrate that aging is associated with an increased mortality rate and greater acute neurological deficits following traumatic brain injury. These data also demonstrate the usefulness of the fluid-percussion model for studying the mechanisms responsible for the age-related increase in vulnerability to brain injury.     

Everyday memory following traumatic brain injury

Residual memory deficits may represent a problem to the everyday functioning of a large number of people, including those who have sustained traumatic brain injury (TBI). The present exploratory study sought to investigate the interrelationships between subjective memory reports, performance on traditional memory tests, and performance on tests of prospective memory. These interrelationships were contrasted between a group of 24 adults who had sustained TBI and a group of 24 matched control subjects. Prospective memory was hypothesized to be indicative of everyday memory functioning. The results provided preliminary evidence that prospective memory tests are sensitive to TBIrelated neurological impairment and, in comparison to traditional tests, may be better indicators of functional memory capacity. This pattern was particularly true for control subjects, possibly because TBI subjects had difficulties in evaluating their memory functioning.     

Neuroplasticity following non-penetrating traumatic brain injury

The primary objective of this review is to examine the methodology and evidence for neuroplasticity operating in recovery from traumatic brain injury (TBI), as compared with previous findings in patients sustaining perinatal and infantile focal vascular lesions. The evidence to date indicates that the traditional view of enhanced reorganization of function after early focal brain lesions might apply to early focal brain lesions, but does not conform with studies of early severe diffuse brain injury. In contrast to early focal vascular lesions, young age confers no advantage in the outcome of severe diffuse brain injury. Disruption of myelination could potentially alter connectivity, a suggestion which could be confirmed through diffusion tensor imaging (DTI). Initial reports of DTI in TBI patients support the possibility that this technique can demonstrate alterations in white matter connections which are not seen on conventional magnetic resonance imaging (MRI) and might change over time or with interventions. Preliminary functional MRI studies of TBI patients indicate alterations in the pattern of brain activation, suggesting recruitment of more extensive cortical regions to perform tasks which stress computational resources. Functional MRI, coupled with DTI and possibly other imaging modalities holds the promise of elucidating mechanisms of neuroplasticity and repair following TBI.     

Perceived needs following traumatic brain injury

OBJECTIVES: (1) Provide population-based estimates of perceived needs following traumatic brain injury (TBI) and the prevalence of unmet needs 1 year postinjury; (2) identify relations among needs that define unique clusters of individuals; and (3) identify risk factors for experiencing selected needs. DESIGN: Telephone survey 1 year after injury of a prospective cohort of all people hospitalized with TBI in the state of Colorado during 2000. MEASURES: Self-reported need for assistance in 13 areas of functioning. RESULTS: A total of 58.8% of persons hospitalized with TBI experienced at least 1 need during the year following injury; 40.2% will experience at least 1 unmet need 1 year after injury. Most frequently experienced needs were "improving your memory, solving problems better" (34.1%), "managing stress, emotional upsets" (27.9%), and "managing your money, paying bills" (23.3%). Cluster analysis revealed 8 distinctive groupings of subjects. If a need existed, those least likely to be met involved cognitive abilities, employment, and alcohol and/or drug use. CONCLUSIONS: Results were consistent with findings from previous assessments of need for services based on surveys of convenience samples; however, the prevalence of unmet needs 1 year after injury may be higher than previously suspected. More post-hospital services addressing cognitive and emotional problems appear needed. Risk factors for experiencing needs suggest potential avenues for clinical intervention.     

Sexual functioning following traumatic brain injury

In this study we investigated sexual functioning in 52 outpatients with a history of traumatic brain injury to determine: (1) the prevalence of reported sexual dysfunction; and (2) the relationship between sexual functioning and age, severity and locus of injury, time since injury, and physical and cognitive function. Reports of sexual functioning indicated a reduction below levels within non-injured populations, but only to statistically significant levels on two scales of the Derogatis Interview of Sexual Function (DISF): Orgasm and Drive/Desire. Location of injury was related to sexuality in that patients with frontal lobe lesions reported an overall higher level of sexual satisfaction and functioning than those individuals without frontal lobe lesions. Time since injury was inversely related to reports of levels of sexual arousal; that is, patients with more recent injuries reported greater levels of arousal than those not recently injured. Right hemisphere injuries also correlated with higher scores on reports of sexual arousal and sexual experiences.     

Psychiatric comorbidity following traumatic brain injury

PRIMARY OBJECTIVE: Survivors of traumatic brain injury (TBI) are at increased risk for development of severe, long-term psychiatric disorders. However, the aetiology of these disorders remains unclear. This article systematically reviews the most current prevalence rates and evidence for causality, in terms of established criteria. MAIN OUTCOME AND RESULTS: Psychiatric syndromes are consistently present at an elevated rate following TBI. Survivors of TBI are particularly susceptible to major depression, generalized anxiety disorder and post-traumatic stress disorder. Evidence for a biological gradient is generally lacking, although this criterion may not be appropriate in the case of TBI. The temporal pattern of onset is variable and reliable critical periods for the post-injury development of a psychiatric disorder remain to be identified; however, individuals appear to remain at risk for years following injury. CONCLUSIONS: Non-organic factors, including pre-morbid personality traits and post-injury psychological reactions to disability and trauma, are implicated in the generation and maintenance of post-TBI psychiatric disorder. There remains insufficient evidence to conclude what role the neuropathological consequences of TBI play in the development of post-TBI psychiatric disorder.     

Effect of N-acetylcysteine on mitochondrial function following traumatic brain injury in rats

Efficacy of N-acetylcysteine (NAC) in traumatic brain injury (TBI)-induced mitochondrial dysfunction was evaluated following controlled cortical impact injury in rats. Respiratory function and calcium transport of rat forebrain mitochondria from injured and uninjured hemispheres were examined. NAC significantly restored mitochondrial electron transfer, energy coupling capacity, calcium uptake activity and reduced calcium content absorbed to brain mitochondrial membranes when examined 12 h post-TBI if NAC was administered i.p. 5 min before injury or 30 min or 1 h postinjury. Glutathione (reduced form, GSH) levels in brain tissues were decreased at all time points examined over a 14-day observation period, while mitochondrial GSH levels significantly decreased only at 3 days and 14 days following TBI. NAC treatment given within 1 h greatly restored brain GSH levels from 1 h to 14 days and mitochondrial GSH levels from 12 h to 14 days post-TBI. NAC did not show protective effects when given 2 h postinjury. Our data indicate that NAC administered postinjury at an early stage can effectively restore TBI-induced mitochondrial dysfunction and the protective effect of NAC may be related to its restoration of GSH levels in the brain.