Optimization of magnesium therapy after severe diffuse axonal brain injury in rats.
A number of studies have demonstrated that magnesium salts given after traumatic brain injury improve subsequent neurologic outcome. However, given that these earlier studies have used a number of different salts, dosages, and routes of administration, follow-up studies of the neuroprotective properties of magnesium are complicated, with comparisons to the earlier literature virtually impossible. The present study has therefore characterized the dose-response characteristics of the most commonly used sulfate and chloride salts of magnesium in a severe model of diffuse traumatic axonal injury in rats. Both magnesium salts improved neurologic outcome in rats when administered as a bolus at 30 min after injury. The i.v. and i.m. optima of each salt was 250 micromol/kg and 750 micromol/kg, respectively. The identical concentrations required for improved neurologic outcome suggest that improvement in outcome was dependent on the magnesium cation and not the associated anion. Subsequent magnetic resonance studies demonstrated that the administered magnesium penetrated the blood-brain barrier after injury and resulted in an increased brain intracellular free magnesium concentration and associated bioenergetic state as reflected in the cytosolic phosphorylation potential. Both of these metabolic parameters positively correlated with resultant neurologic outcome measured daily in the same animals immediately before the magnetic resonance determinations. (+info)
N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain.
Morbidity and mortality from head trauma is highest among children. No animal model mimicking traumatic brain injury in children has yet been established, and the mechanisms of neuronal degeneration after traumatic injury to the developing brain are not understood. In infant rats subjected to percussion head trauma, two types of brain damage could be characterized. The first type or primary damage evolved within 4 hr and occurred by an excitotoxic mechanism. The second type or secondary damage evolved within 6-24 hr and occurred by an apoptotic mechanism. Primary damage remained localized to the parietal cortex at the site of impact. Secondary damage affected distant sites such as the cingulate/retrosplenial cortex, subiculum, frontal cortex, thalamus and striatum. Secondary apoptotic damage was more severe than primary excitotoxic damage. Morphometric analysis demonstrated that the N-methyl-D-aspartate receptor antagonists 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonate and dizocilpine protected against primary excitotoxic damage but increased severity of secondary apoptotic damage. 2-Sulfo-alpha-phenyl-N-tert-butyl-nitrone, a free radical scavenger, did not affect primary excitotoxic damage but mitigated apoptotic damage. These observations demonstrate that apoptosis and not excitotoxicity determine neuropathologic outcome after traumatic injury to the developing brain. Whereas free radical scavengers may prove useful in therapy of head trauma in children, N-methyl-D-aspartate antagonists should be avoided because of their propensity to increase severity of apoptotic damage. (+info)
One year outcome in mild to moderate head injury: the predictive value of acute injury characteristics related to complaints and return to work.
OBJECTIVES: To determine the prognostic value of characteristics of acute injury and duration of post-traumatic amnesia (PTA) for long term outcome in patients with mild to moderate head injury in terms of complaints and return to work. METHODS: Patients with a Glasgow coma score (GCS) on admission of 9-14 were included. Post-traumatic amnesia was assessed prospectively. Follow up was performed at 1, 3, 6, and 12 months after injury. Outcome was determined by the Glasgow outcome scale (GOS) 1 year after injury and compared with a more detailed outcome scale (DOS) comprising cognitive and neurobehavioural aspects. RESULTS: Sixty seven patients were included, mean age 33.2 (SD 14.7) years and mean PTA 7.8 (SD 7.3) days. One year after injury, 73% of patients had resumed previous work although most (84%) still reported complaints. The most frequent complaints were headache (32%), irritability (34%), forgetfulness and poor concentration (42%), and fatigue (45%). According to the GOS good recovery (82%) or moderate disability (18%) was seen. Application of the DOS showed more cognitive (40%) and behavioural problems (48%), interfering with return to work. Correlation between the GOS and DOS was high (r=0.87, p<0.01). Outcome correlated with duration of PTA (r=-0.46) but not significantly with GCS on admission (r=0.19). In multiple regression analysis, PTA and the number of complaints 3 months after injury explained 49% of variance on outcome as assessed with the GOS, and 60% with the DOS. CONCLUSIONS: In mild to moderate head injury outcome is determined by duration of PTA and not by GCS on admission. Most patients return to work despite having complaints. The application of a more detailed outcome scale will increase accuracy in predicting outcome in this category of patients with head injury. (+info)
Parkinson's syndrome after closed head injury: a single case report.
A 36 year old man, who sustained a skull fracture in 1984, was unconscious for 24 hours, and developed signs of Parkinson's syndrome 6 weeks after the injury. When assessed in 1995, neuroimaging disclosed a cerebral infarction due to trauma involving the left caudate and lenticular nucleus. Parkinson's syndrome was predominantly right sided, slowly progressive, and unresponsive to levodopa therapy. Reaction time tests showed slowness of movement initiation and execution with both hands, particularly the right. Recording of movement related cortical potentials suggested bilateral deficits in movement preparation. Neuropsychological assessment disclosed no evidence of major deficits on tests assessing executive function or working memory, with the exception of selective impairments on the Stroop and on a test of self ordered random number sequences. There was evidence of abulia. The results are discussed in relation to previous literature on basal ganglia lesions and the effects of damage to different points of the frontostriatal circuits. (+info)
Cerebral blood flow in the monkey after focal cryogenic injury.
A focal cryogenic lesion was made in the left superior frontal gyrus of the anesthetized macaque brain. Cerebral blood flow (CBF) was determined by the hydrogen clearance technique before and during the 4 hours following trauma. Local CBF in tissue adjacent to the lesion increased in the first half hour after the lesion was made and then decreased during the ensuing 3 1/2 hours. Local CBF in the contralateral superior frontal gyrus, as well as total CBF and oxygen consumption, were unchanged by cryogenic trauma. The spread of vasogenic edema into uninjured tissue probably accounts for the observed decrease in local CBF. This experimental model may assist in discovering therapy to alter favorably the spatial and temporal profile of pathologic CBF changes in tissue surrounding an acute lesion of the brain. (+info)
An intrathecal bolus of cyclosporin A before injury preserves mitochondrial integrity and attenuates axonal disruption in traumatic brain injury.
Traumatic brain injury evokes multiple axonal pathologies that contribute to the ultimate disconnection of injured axons. In severe traumatic brain injury, the axolemma is perturbed focally, presumably allowing for the influx of Ca2+ and initiation of Ca2+ -sensitive, proaxotomy processes. Mitochondria in foci of axolemmal failure may act as Ca2+ sinks that sequester Ca2+ to preserve low cytoplasmic calcium concentrations. This Ca2+ load within mitochondria, however, may cause colloid osmotic swelling and loss of function by a Ca2+ -induced opening of the permeability transition pore. Local failure of mitochondria, in turn, can decrease production of high-energy phosphates necessary to maintain membrane pumps and restore ionic balance in foci of axolemmal permeability change. The authors evaluated the ability of the permeability transition pore inhibitor cyclosporin A (CsA) to prevent mitochondrial swelling in injured axonal segments demonstrating altered axolemmal permeability after impact acceleration injury in rat. At the electron microscopic level, statistically fewer abnormal mitochondria were seen in traumatically injured axons from CsA-pretreated injured animals. Further, this mitochondrial protection translated into axonal protection in a second group of injured rats, whose brains were reacted with antibodies against amyloid precursor protein, a known marker of injured axons. Pretreatment with CsA significantly reduced the number of axons undergoing delayed axotomy, as evidenced by a decrease in the density of amyloid precursor protein-immunoreactive axons. Collectively, these studies demonstrate that CsA protects both mitochondria and the related axonal shaft, suggesting that this agent may be of therapeutic use in traumatic brain injury. (+info)
Evaluating methods for estimating premorbid intellectual ability in closed head injury.
OBJECTIVES: The present study examines the utility of three measures of premorbid intellectual functioning in closed head injury, the National adult reading test (NART), the Cambridge contextual reading test (CCRT), and the spot the word test (STW). METHODS: In the first experiment, a group of 25 patients with closed head injury were compared with 50 healthy controls and 20 orthopaedic trauma controls. In the second experiment, the strength of correlation between the premorbid measures and current intellectual level were assessed in 114 healthy adults. RESULTS: The head injured group performed significantly more poorly than both control groups on measures of current intellectual ability. However, no significant differences emerged between the groups on any of the premorbid measures. In the large control sample, both the NART and the CCRT accounted for about 50% of the variance in current verbal intelligence. However, by contrast, the STW only accounted for 29% of the variability in verbal intelligence. Adding demographic variables to the prediction of current intellectual level increased the amount of variance explained to 60% for the NART, 62% for the CCRT, but only 41% for the STW. CONCLUSION: The results provide supportive evidence for the use of the CCRT and NART in estimating premorbid intellectual functioning in patients who have sustained closed head injuries, but suggest caution when employing the STW. (+info)
Frozen in time: life in the face of chronic care cutbacks.
Kathy Cook won the $750 first prize in CMAJ's 7th Annual Amy Chouinard Memorial Essay Contest. The deadline for entries to the contest, which is designed to stimulate interest in medical writing among journalism students, is June 1. Entries should be forwarded to the news and features editor. In her winning essay, Cook explores the frustrations and quality-of-life issues that arise in a chronic care institution that is trying to operate in the midst of serious funding cuts. (+info)