Awareness and distress after traumatic brain injury: a relative's perspective

OBJECTIVE: To examine the relationship between relatives' distress level and their ratings of impaired awareness for persons with traumatic brain injury (TBI). DESIGN AND OUTCOME MEASURES: Participants were 25 patients with TBI, 16 with probably dementia, and 15 with memory complaints but no dementia. Participants completed the Barrow Neurological Institute Screen for Higher Cerebral Functions. Relatives of all patients completed the Patient Competency Rating Scale (Relative Form). Relatives also rated their distress level on a scale from 0 (no distress) to 10 (severe distress) and then rated the patient's level of awareness of their difficulties, also on a scale from 0 (not aware) to 10 (completely aware). SETTING: Clinical neuropsychology outpatient service of a neurological institute and medical center. RESULTS: For relatives of patients with TBI, a significant correlation of -0.52 (P = .006) was found. Correlations for the dementia and memory complaint groups were -0.62 (P = .03) and -0.39 (P = .20), respectively. CONCLUSIONS: The presence of brain dysfunction associated with neuropsychological disturbances appears to influence the magnitude of the relationship between the distress level of family members and their ratings of impaired awareness in persons with TBI.     

Isoflurane: a comparison of its metabolism by human and rat hepatic cytochrome P-450

Isoflurane is metabolized by both rat and human hepatic microsomal cytochrome P-450 in vitro to fluoride ion and organofluorine metabolites. The forms of rat liver microsomal cytochrome P-450 induced by phenobarbital and pregnenolone-16 alpha-carbonitrile appear to be involved in the metabolism of isoflurane, while the forms induced by beta-naphthoflavone do not. Different pathways are favored for the metabolism of isoflurane by rat and by human liver microsomes: trifluoroacetaldehyde appears to be produced from isoflurane by rat liver microsomal cytochrome P-450, while trifluoroacetate or other nonvolatile fluorinated metabolites were not. The trifluoroacetaldehyde so produced binds tightly to microsomal constituents. Human liver microsomes converted isoflurane extensively to nonvolatile fluorinated products, one of which appears to be trifluoroacetate. The proposed pathways for the metabolism of isoflurane are considered in view of the above results.     

Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.     

Alcohol and drug use following traumatic brain injury: a prospective study

PRIMARY OBJECTIVES: To establish pre-morbid alcohol and drug use in persons with TBI, relative to controls, investigate how patterns of substance use change over time following TBI and identify factors associated with heavy post-injury substance use. METHODS AND PROCEDURES: The Alcohol Use Disorders Identification test (AUDIT) and Drug Abuse Screening Test (DAST) was completed by 121 hospital inpatients with TBI, documenting pre-injury alcohol and drug use, and 133 demographically similar controls. Participants with TBI completed these measures and the Hospital Anxiety and Depression Scale (HADS) again 1 and 2 years post-injury and 76 also completed them at 3 years. RESULTS: Participants with TBI showed similar levels of drug and alcohol use to controls pre-injury, with 31.4% of the TBI group and 29.3% of controls drinking at hazardous levels. Alcohol and drug use declined in the first year post-injury, but increased by 2 years post-injury, with only 21.4% of participants with TBI reporting abstinence from alcohol and 25.4% drinking at hazardous levels. Only 9% showed a drug problem, but 24% had returned to some drug use. Those showing heavy alcohol use post-injury were young, male and heavy drinkers pre-injury. Drug and alcohol use was similar at 3 years post-injury. CONCLUSIONS: More active intervention is needed to reduce alcohol and drug use following TBI.     

Differential effects of the anticonvulsant topiramate on neurobehavioral and histological outcomes following traumatic brain injury in rats

The efficacy of topiramate, a novel therapeutic agent approved for the treatment of seizure disorders, was evaluated in a model of traumatic brain injury (TBI). Adult male rats were anesthetized (sodium pentobarbital, 60 mg/kg, i.p.), subjected to lateral fluid percussion brain injury (n = 60) or sham injury (n = 47) and randomized to receive either topiramate or vehicle at 30 min (30 mg/kg, i.p.), and 8, 20 and 32 h postinjury (30 mg/kg, p.o.). In Study A, memory was evaluated using a Morris water maze at 48 h postinjury, after which brain tissue was evaluated for regional cerebral edema. In Study B, animals were evaluated for motor function at 48 h and 1, 2, 3, and 4 weeks postinjury using a composite neuroscore and the rotating pole test and for learning ability at 4 weeks. Brains were analyzed for hemispheric tissue loss and hippocampal CA3 cell loss. Topiramate had no effect on posttraumatic cerebral edema or histologic damage when compared to vehicle. At 48 h, topiramate treatment improved memory function in sham but not brain-injured animals, while at one month postinjury it impaired learning performance in brain-injured but not sham animals. Topiramate significantly improved composite neuroscores at 4 weeks postinjury and rotating pole performance at 1 and 4 weeks postinjury, suggesting a potentially beneficial effect on motor function following TBI.     

The effect of chronic renal failure on hepatic drug metabolism and drug disposition

There is abundant evidence that chronic renal failure (CRF) and end-stage renal disease (ESRD) alter drug disposition by affecting protein and tissue binding and reducing systemic clearance of renally cleared drugs. What is not fully appreciated is that CRF can significantly reduce nonrenal clearance and alter the bioavailability of drugs predominantly metabolized by the liver. Animal studies in CRF have shown a major down-regulation (40-85%) of hepatic cytochrome P-450 metabolism involving specific isozymes. Phase II reactions such as acetylation and glucuronidation are also involved, with some isozymes showing induction and others inhibition. Hepatic enzymes exhibiting genetic polymorphisms such as N-acetyl-transferase-2 (NAT-2), which is responsible for the rapid and slow acetylator phenotypes, have been shown to be inhibited by ESRD and reversed by transplantation. There is some evidence pointing to the possibility of inhibitory factors circulating in the serum in ESRD patients which may be dialyzable. This review includes all significant animal and clinical studies using the search terms "chronic renal failure,"cytochrome P-450," and "liver metabolism" over the past 10 years obtained from the National Library of Medicine MEDLINE database, including relevant articles back to 1969.     

Cerebrovascular connexin expression: effects of traumatic brain injury

Traumatic brain injury (TBI) results in dysfunction of the cerebrovasculature. Gap junctions coordinate vasomotor responses and evidence suggests that they are involved in cerebrovascular dysfunction after TBI. Gap junctions are comprised of connexin proteins (Cxs), of which Cx37, Cx40, Cx43, and Cx45 are expressed in vascular tissue. This study tests the hypothesis that TBI alters Cx mRNA and protein expression in cerebral vascular smooth muscle and endothelial cells. Anesthetized (1.5% isoflurane) male Sprague-Dawley rats received sham or fluid-percussion TBI. Two, 6, and 24?h after, cerebral arteries were harvested, fresh-frozen for RNA isolation, or homogenized for Western blot analysis. Cerebral vascular endothelial and smooth muscle cells were selected from frozen sections using laser capture microdissection. RNA was quantified by ribonuclease protection assay. The mRNA for all four Cx genes showed greater expression in the smooth muscle layer compared to the endothelial layer. Smooth muscle Cx43 mRNA expression was reduced 2 h and endothelial Cx45 mRNA expression was reduced 24 h after injury. Western blot analysis revealed that Cx40 protein expression increased, while Cx45 protein expression decreased 24 h after injury. These studies revealed significant changes in the mRNA and protein expression of specific vascular Cxs after TBI. This is the first demonstration of cell type-related differential expression of Cx mRNA in cerebral arteries, and is a first step in evaluating the effects of TBI on gap junction communication in the cerebrovasculature.     

Behavioural and cognitive changes in traumatic brain injury: A spouse's perspective

A single case study is presented that reviews the behavioural and emotional changes in a traumatic brain injury patient from the perspective of the spouse.     

Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.     

酮体代谢在颅脑创伤中对脑组织的神经保护作用

【摘要】〓外伤性脑损伤后造成脑组织缺血缺氧,继发炎症、脑血肿、脑肿胀、脑水肿、颇内压升高等一系列病理生理学变化。在颅脑创伤中,继发性颅脑损伤是引起急性病情恶化和招致病人死亡、致残的主要原因。颅脑创伤后会出现葡萄糖代谢障碍,从而影响神经元的代谢和能量来源。生酮饮食是一种高脂肪、低碳水化合物、低蛋白的饮食治疗方案,机体主要依靠脂肪而不是碳水化合物来供应能量,已用于临床抗癫痫的治疗,其有效性和安全性已得到国际公认。近来有报道证实颅脑创伤后生酮饮食可以延缓细胞调亡,起到神经保护作用,并能减轻脑水肿。现就酮体代谢对颅脑创伤后的神经保护作用进行综述。     

Disturbances of self-awareness and rehabilitation of patients with traumatic brain injury: a 20-year perspective

Over the last 20 years, numerous papers that are relevant to understanding the problem of impaired self-awareness after moderately severe to severe traumatic brain injury have appeared. This article reviews many of these papers and summarizes salient findings relevant to rehabilitation and future research.     

Alcohol and drug use following traumatic brain injury: A prospective study

Primary objectives: To establish pre-morbid alcohol and drug use in persons with TBI, relative to controls, investigate how patterns of substance use change over time following TBI and identify factors associated with heavy post-injury substance use.

Methods and procedures: The Alcohol Use Disorders Identification test (AUDIT) and Drug Abuse Screening Test (DAST) was completed by 121 hospital inpatients with TBI, documenting pre-injury alcohol and drug use, and 133 demographically similar controls. Participants with TBI completed these measures and the Hospital Anxiety and Depression Scale (HADS) again 1 and 2 years post-injury and 76 also completed them at 3 years.

Results: Participants with TBI showed similar levels of drug and alcohol use to controls pre-injury, with 31.4% of the TBI group and 29.3% of controls drinking at hazardous levels. Alcohol and drug use declined in the first year post-injury, but increased by 2 years post-injury, with only 21.4% of participants with TBI reporting abstinence from alcohol and 25.4% drinking at hazardous levels. Only 9% showed a drug problem, but 24% had returned to some drug use. Those showing heavy alcohol use post-injury were young, male and heavy drinkers pre-injury. Drug and alcohol use was similar at 3 years post-injury.

Conclusions: More active intervention is needed to reduce alcohol and drug use following TBI.     

Changes in bone metabolism in a rat model of traumatic brain injury

PRIMARY OBJECTIVE: To evaluate the process of bone metabolism after traumatic brain injury. RESEARCH DESIGN: Randomized controlled trial. METHODS AND PROCEDURES: Rats were randomly assigned to either the brain injury group or to the sham-operation group using a fluid percussion device. The BMDs of lumbar vertebrae and proximal femur and bone turnover markers, osteocalcin and carboxy-terminal telopeptide, were measured at three points: the day before surgery and 1 and 3 weeks post-operatively. The biomechanics (maximum load of tibia and femoral neck) were measured 3 weeks post-operatively. MAIN OUTCOMES AND RESULTS: There was significant change in the BMDs of lumbar vertebrae 1 week post-operatively and of both distal femurs 3 weeks post-operatively (p < 0.05). A significant change in the maximum load of femoral neck was also observed 3 weeks post-operatively between the brain injury and the sham-operation groups (p = 0.044). CONCLUSIONS: This finding suggests that brain injury could induce osteoporosis by immobilization.     

Neurobehavioral effects of amantadine after pediatric traumatic brain injury: a preliminary report

OBJECTIVE: To investigate the safety and efficacy of a dopamine agonist, amantadine hydrochloride (AMH), in the treatment of neurobehavioral sequelae of pediatric TBI. PROCEDURES: Age- and severity-matched traumatic brain injury groups, randomized to AMH (n = 17) or usual care (n = 10), completed behavior scales and neuropsychological tests. Effect sizes measured the treatment effect within subjects and between groups. Side effects were tracked over the 12-week study course. RESULTS: Behavior improved in the AMH group, but only those 2 years or fewer postinjury showed a treatment effect on cognitive tests. CONCLUSIONS: After traumatic brain injury, a 12-week course of AMH was safe and, according to parent report, improved behavior. AMH may have the potential to improve cognition in more recently injured children.     

Mild traumatic brain injury: effects on naming in word retrieval and discourse

PRIMARY OBJECTIVE: To investigate differences between a group with mild traumatic brain injury (MTBI) and a control group relative to standard scores and error type during word retrieval in both naming and discourse tasks. METHODS AND PROCEDURES: Ten participants with MTBI were age-, gender- and education-matched with 10 participants without injury. Pre-experimental tasks for the participants with MTBI included the Scales of Cognitive Ability for Traumatic Brain Injury and the Raven's Coloured Progressive Matrices and both groups received the Peabody Picture Vocabulary Test-III. Experimental tasks included the Test of Adolescent/Adult Word Finding and the Test of Word Finding in Discourse. MAIN OUTCOMES AND RESULTS: Few participants (three on each experimental task) demonstrated psychometrically-based word retrieval deficits (standard score < 85); however, a significant difference in performance for the TAWF as compared to the TWFD was observed between groups. More word finding errors occurred with confrontational naming than with discourse tasks for both groups, with latency as the primary error type. CONCLUSIONS: Confrontational naming tasks may be more sensitive to subtle language difficulties occurring after MTBI. The study of adults with MTBI and their performance on semantically-based tasks offers important information for the advancement of therapeutic intervention and education.