摘要:

ABSTRACTRecent studies have demonstrated a neuroprotective effect of mild/moderate hypothermia in models of cerebral trauma and ischemia. In contrast, hypotension is known to exacerbate CNS injury. To better understand the mechanisms whereby hypothermia and hypotension influence secondary neural injury, the present study assessed the effects of these two variables upon blood–brain barrier (BBB) permeability following controlled cortical impact injury. Rats were subjected to either 0, 15, or 30 min of hypotension under normothermic or slightly hypothermic brain temperature conditions. Brain temperature was maintained within 0.5°C of baseline (normothermic) or allowed to float freely (e.g., become hypothermic) throughout the study. Hypotension was induced immediately after head injury by rapid hemorrhage down to a mean arterial pressure of 50 mm Hg and held there for 15 or 30 min. Blood–brain barrier permeability was measured by the extravasation of plasma protein-bound Evan's blue dye into the injured cortex at 60 min postinjury. The results revealed that mild hypothermia (<1.6 ± 0.2°C), right before and 15–30 min following head injury, significantly reduced BBB permeability 28.0, 21.8, and 26.2% in rats subjected to 0, 15, or 30 min hypotension, respectively (allpvalues ≤ 0.05). Hypotension did not increase BBB permeability nor did it significantly interact with the brain temperature effect. Previous results, using this same model, have shown that the progressive posttraumatic increase in BBB permeability is preceded by an increase in cortical.OH and lipid hydroperoxides at the site of injury and is attenuated by the lipid peroxidation inhibitor tirilazad mesylate. Thus, the present results are discussed in terms of the role of free radical-induced lipid peroxidation in the genesis of posttraumatic BBB damage and the possible effects of hypothermia upon this inju

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.1

年代:1996

数据来源: MAL

摘要:

ABSTRACTThis study investigates the effect of the NO synthase inhibitors, NG-nitro l-arginine methyl ester (l-NAME) and 7-nitro indazole (7-NI), on the neurological deficit 24 h after a moderate closed head injury in mice. Low doses ofl-NAME or 7-NI given soon after the injury significantly reduced the neurological deficit compared to the vehicle-treated group.l-Arginine (300 mg/kg) did not alter the neurological deficit, but reversed the protective effects of bothl-NAME and 7-NI when given at the same time. Bothl-NAME and 7-NI had dose-related effects. The neuroprotective effects ofl-NAME and 7-NI occurred when the drugs were given 5, 30, or 60 min after brain injury, but not when treatment was begun 2 h after brain injury, suggesting a short therapeutic window for both drugs. These results suggest that NO synthesis by neuronal NO synthase plays an important role in the early neurotoxic cascade leading to neurological deficit following traumatic brain injury.

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.11

年代:1996

数据来源: MAL

摘要:

ABSTRACTCerebral ischemic insults occur in at least 30% of severely head injured patients at a very early stage following trauma and are associated with early death. To date, the threshold for ischemia of 18 mL/100 g/min used in human head injury studies has been adopted from animal studies (by temporary occlusion of the middle cerebral artery). Since the traumatized brain becomes more susceptible to irreversible damage if accompanied by ischemia one may question whether the threshold for ischemic vulnerability is higher than 18 mL/100 g/min. Cerebral ischemia can cause atrophy. Therefore, the authors obtained computerized tomography (CT) scans in 33 comatose head-injured patients (Glasgow Coma Score of 8 or less) at least 3 months following injury and compared ventricle sizes (as a reflection of atrophy) with cerebral blood flow (CBF) obtained within 4 h (average 2.3 ± 0.8 h) after injury. Ventricular measurements were performed in three fashions: the third ventricular size (cm), the bicaudate cerebral ventricular index (BCVI), and the hemispheric ventricular index (HCVI). No significant correlation was found between early CBF and any of the ventricle sizes. Applying a multiple correlation analysis with four independent parameters [CBF, CBF/time postinjury, CBF/(time postinjury)2, age], only age emerged as a significant indicator for predicting ventricle size (p<0.001). We also compared CBF data, obtained within 4 h after trauma, from survivors at 3 months after injury (mean CBF of 32 mL/100 g/min) with CBF data from nonsurvivors (CBF 20 mL/100 g/min). The difference in CBF between survivors and nonsurvivors was significant atp<0.001 (Wilcoxon rank-sum test). The proportion of patients with CBF less than or equal to 20 mL/100 g/min was 56% in the nonsurvivors and only 5% in survivors. The difference in the proportions was significant atp<0.001 (chi-square test). We conclude that a measure of atrophy does not correlate with ultra-early CBF. However, based on the clear distinction between survivors and nonsurvivors, we suggest the threshold for ischemia after head injury be redefined as a CBF of 20 mL/100 g/min

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.17

年代:1996

数据来源: MAL

摘要:

ABSTRACTSixty-eight patients were entered into a randomized, prospective, double-blinded controlled trial of supplemental zinc versus standard zinc therapy to study the effects of zinc supplementation on neurologic recovery and nutritional/metabolic status after severe closed head injury. One month after injury, the mortality rates in the standard zinc group and the zinc-supplemented group were 26 and 12%, respectively. Glasgow Coma Scale (GCS) scores of the zinc-supplemented group exceeded the adjusted mean GCS score of the standard group at day 28 (p= 0.03). Mean motor GCS score levels of the zinc-supplemented group were significantly higher on days 15 and 21 than those of the control group (p= 0.005,p= 0.02). This trend continued on day 28 of the study (p= 0.09). The groups did not differ in serum zinc concentration, weight, energy expenditure, or total urinary nitrogen excretion after hospital admission. Mean 24-h urine zinc levels were significantly higher in the zinc-supplemented group at days 2 (p= 0.0001) and 10 (p= 0.01) after injury. Mean serum prealbumin concentrations were significantly higher in the zinc-supplemented group (p= 0.003) at 3 weeks after injury. A similar pattern was found for mean serum retinol binding protein level (p= 0.01). A significantly larger number of patients in the standard zinc group had craniotomies for evacuation of hematoma; thus a bias may have been present. The results of this study indicate that zinc supplementation during the immediate postinjury period is associated with improved rate of neurologic recovery and visceral protein concentrations for patients with severe closed head injury.

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.25

年代:1996

数据来源: MAL

摘要:

ABSTRACTMagnetic resonance scans of 63 TBI patients were analyzed to examine the relationship between injury severity, lesion volume (nonthalamic cortical/subcortical lesions), ventricle-to-brain ratio (VBR), and thalamic volume. For comparison, 33 normal control subjects were used. Patients with visible nonthalamic structural lesions showed significantly smaller thalamic volumes than patients without visible lesions or control subjects. Results also indicated that patients with visible lesions had significantly more severe injuries than patients without lesions. Patients with moderate–severe injuries had significantly smaller thalamic volumes and greater VBRs than patients with mild–moderate injuries. Although several variables related to thalamic volume, the presence of nonthalamic lesions was sufficient to result in smaller thalamic volume. Decreased thalamic volume following head injury suggests that subcortical brain structures may be susceptible to transneuronal degeneration following cortical lesions, and that this can be detected byin vivoMR-based volumetric analy

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.35

年代:1996

数据来源: MAL

摘要:

ABSTRACTThis study was designed to determine whether exposure to a complex environment after traumatic brain injury (TBI) would promote the recovery of cognitive function. Rats were injured at a moderate level of fluid percussion injury (2.1 atm) or were prepared for injury but were not injured (sham injury). Immediately after the injury or sham injury, the injured/complex (n= 8) and the sham/complex (n= 7) groups were placed into a complex environment. The complex environment was a 89 × 89-cm enclosure with different types of bedding and objects that provided motor, olfactory, tactile, and visual stimulation. The injured/standard (n= 8) and the sham/standard (n= 8) groups were returned to the animal vivarium where they were housed individually in standard wire mesh cages (24 × 20 × 18 cm). On days 11–15 (postinjury), performance in the Morris water maze was assessed. Analysis of the latency to reach the goal platform indicated that injured animals recuperating in the complex environment performed significantly better than injured animals recovering in the standard environment (p<0.01). In fact, injured animals in the complex environment performed as well as both sham-injured groups. The improved performance of injured rats recovering in the enriched environment occurred in the absence of environmentally induced alterations in brain weight. These results indicate that exposure to environmental complexity enhances recovery of cognitive function after

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.41

年代:1996

数据来源: MAL

摘要:

ABSTRACTHU-211 is a novel synthetic analog of tetrahydrocannabinol that was recently shown in animal models to be nonpsychotropic. In this study we show that HU-211 can potentially be used as a neuroprotective compound in the CNS. Using a calibrated crush injury of adult rat optic nerve, we show that HU-211 can reduce injury-induced metabolic and electrophysiological deficits. Energy metabolism was monitored by measuring the intramitochondrial nicotine-amine adenine dinucleotide redox state hourly for 6 h after injury and treatment. Electrophysiological activity was assessed by compound action potential and visual evoked potential response. Beneficial effects were dose-dependent, being optimal at 7 mg/kg, administered intraperitoneally. The time window during which treatment was effective was found to be from the time of injury for at least 5 h, with treatment most effective at the time of injury. These results strongly suggest that HU-211, given immediately after CNS injury at the optimal dosage, may possess neuroprotective activities.

ISSN:0897-7151    

DOI:10.1089/neu.1996.13.49

年代:1996

数据来源: MAL