摘要:

ABSTRACTQuantitative analyses were performed on magnetic resonance images (MRIs) obtained from the brains of 31 traumatic brain-injured (TBI) patients and 25 normal control subjects. The quantitative analyses involved comparisons of the shapes of proton density gray scale pixel histograms obtained from both 3-mm and 5-mm slice thickness. Image segmentation was accomplished by a multispectral fuzzy C-means and/or k-nearest-neighbor (kNN) algorithms and manual classification was used to label segmented classes into CSF, white matter, gray matter, and other. Shape descriptors were derived from the pixel intensity histograms of the combined gray matter and white matter classes for each MRI slice. Statistical analyses revealed significant differences in pixel intensity distributions between TBI and control subjects. Normal control subjects tended to exhibit bimodal gray matter–white matter histograms, whereas, TBI patients tended to exhibit unimodal gray matter–white matter histograms. In the control subjects the pixels intermediate in intensity between gray and white matter were located primarily at the border between the gray and white matter, whereas TBI patients exhibited a thickening of the number of intermediate pixels at the border as well as an increase in intermediate pixels in the middle of the gray and white matter. The greater the severity of TBI, then the larger the number of intermediate intensity pixels within and between gray and white matter. Further analyses demonstrated shifts in magnetic resonance relaxation times in gray and white matter in TBI patients, which suggested that the tendency toward unimodality in TBI patients represents a pathological reduction in brain differentiation due to measurable biophysical change.Key words:quantitative MRI; pixel intensity change; traumatic brain in

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.1

年代:1997

数据来源: MAL

摘要:

ABSTRACTA reliable and rapid method for quantifying lesion volume following traumatic brain injury (TBI) has vast potential in brain injury research. Staining with 2,3,5-triphenyltetrazolium chloride (TTC) provides for demarcation of damaged or infarcted tissue from normal, viable cerebral tissue, in which a red formazan product is formed by reduction during cellular respiration of mitochondrial dehydrogenase enzymes. The present study evaluated the use of TTC staining to quantify the cortical lesion volume in rats undergoing fluid-percussion (FP) brain injury. Male Sprague–Dawley rats (350–450 g,n= 27) were anesthetized (sodium pentobarbital, 60 mg/kg, ip) and subjected to lateral FP brain injury of mild (1.1–1.3 atm,n= 5), moderate (2.0–2.3 atm,n= 9), or high (2.4–2.6 atm,n= 8) severity, while sham (noninjured) animals (n= 5) were anesthetized and surgically prepared without injury. Forty-eight hours after injury animals were sacrificed, brains were stained with TTC, and lesion volumes were calculated. A highly significant correlation was found between cerebral cortical lesion volume (mm3) and severity of brain injury (r= 0.85;p<0.0001). The mean (± SD) lesion volumes were 12.1 (± 4.5) mm3following mild injury, 33.8 (± 8.6) mm3following moderate injury, and 45.1 (± 14.0) mm3following severe injury. A significant difference was observed between all injury groups using attest with Bonferroni correction (p<0.05). These results suggest that the TTC staining technique is a useful, rapid, and reproducible method for quantification of lesion volume following lateral FP brain injury.Key words:brain injury, histopathology, lateral fluid-percussion, lesion volume, m

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.15

年代:1997

数据来源: MAL

摘要:

ABSTRACTTraumatic brain injury (TBI) is associated with primary and secondary injury. A thorough understanding of secondary injury will help to develop effective treatments and improve patient outcome. In this study, the GM model of controlled cortical impact injury (CCII) of Lighthall (1988) was used with modification to induce lateral TBI in rats. Forebrain mitochondria isolated from ipsilateral (IH) and contralateral (CH) hemispheres to impact showed a distinct difference. With glutamate + malate as substrates, mitochondria from the IH showed a significant decrease in State 3 respiratory rates, respiratory control indices (RCI), and P/O ratios. This decrease occurred as early as 1 h and persisted for at least 14 days following TBI. The State 3 respiratory rates, RCI, and P/O ratios could be restored to sham values by the addition of EGTA to the assay mixture. A significant amount of Ca2+was found to be adsorbed to the mitochondria of both the IH and the CH with higher values seen in the IH. The rate of energy-linked Ca2+transport in the IH was significantly decreased at 6 and 12 h. These data indicate that CCII-induced TBI perturbs cellular Ca2+homeostasis and results in excessive Ca2+adsorption to the mitochondrial membrane, which subsequently inhibits the respiratory chain-linked electron transfer and energy transduction.Key words:brain mitochondria, Ca2+, oxidative phosphorylation, rat, traumatic brain injury

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.23

年代:1997

数据来源: MAL

摘要:

ABSTRACTSerotonin has been implicated in the pathobiology of central nervous system trauma. Using micro-dialysis techniques, we performed measurements of extracellular serotonin release within the traumatized cerebral cortex of rats subjected to moderate fluid-percussion (F-P) brain injury. Twenty-four hours prior to TBI, a F-P interface was positioned parasagitally over the right cerebral cortex. On the second day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37–37.5°C), rats were injured (n= 6) with a F-P pulse ranging from 1.8 to 2.0 atm. Following trauma, brain temperature was maintained for 4 h at 37°C. Sham trauma animals (n= 7) were treated in an identical manner. Brain trauma induced acute elevations in the extracellular levels of serotonin (p<0.01, ANOVA) compared to sham-operated controls. For example, serotonin levels increased from 18.85 ± 7.12 pm/mL (mean ± SD) in baseline samples to 65.78 ± 11.36 in the first 10 min after trauma. The levels of serotonin remained significantly higher than control for the first 90-min sampling period. In parallel to the increase in serotonin levels after TBI, a significant 71.1% decrease (i.e., 182.29 ± 30.08 vs 52.75 ± 16.92) in extracellular 5-hydroxyindoleacetic acid (5-HIAA) levels was observed during the first 10 min after TBI. These data indicate that TBI is followed by a prompt increase in the extracellular levels of serotonin in cortical regions adjacent to the impact site. These neurochemical findings indicate that serotonin may play a significant role in the patho-physiology of TBI.Key words:traumatic brain injury, serotonin, micr

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.35

年代:1997

数据来源: MAL

摘要:

ABSTRACTExperimental enhancement of noradrenergic activity following traumatic brain injury (TBI) accelerates behavioral recovery if performed at a time when brain norepinephrine (NE) turnover is decreased. But, since NE turnover is markedly increased immediately after TBI, the present study was undertaken to evaluate the effect of modulating these early changes in NE metabolism on recovery of function. Rats were pretrained on a modified beam walking task. Thirty minutes prior to unilateral somatosensory cortex contusion they were treated with a NE reuptake blocker [desmethylimipramine (DMI); 10 mg/kg, ip,n= 6] or an α1-adrenoreceptor antagonist [prazosin (PRZ); 3 mg/kg, ip,n= 6]. PRZ pretreatment markedly worsened beam walking performance throughout the 3 weeks following injury, whilst DMI pretreatment did not affect performance compared to injured controls (n= 4). Despite the marked behavioral deficits, PRZ-treated animals showed no apparent worsening of histological damage (n= 11 per group) and lesion size was the same in all groups. In separate experiments (n= 4 per group), PRZ lowered basal blood pressure and prevented the rise in pressure immediately following TBI. However, blood pressures in the three groups came to the same level within 20 sec following TBI. This suggests that the action of PRZ was not simply due to hypotension-induced ischemia. It is possible that blockade of α1-adrenoreceptors in the immediate posttrauma period leads to enhancement of excitatory neurotransmission, which exacerbates behavioral deficits.Key words:contusion, desmethylimipramine, head trauma, norepinephrine, pharmacology, prazosin, somatosensory cort

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.43

年代:1997

数据来源: MAL

摘要:

ABSTRACTWe have investigated the effect of memantine, a clinically used NMDA receptor antagonist, in two experimental animal models of spinal cord injury. The lesions were laser-induced photothrombosis to induce focal spinal cord ischemia and clip compression to mimic traumatic spinal cord injury. Pre- or posttreatment of rats with a dose of memantine (20 mg/kg ip) previously shown to be neuroprotective in cerebral ischemia, failed to affect both the neurological and morphological outcome of ischemic spinal cord injury. Likewise, memantine had no effects on neurological and morphological outcome after experimental traumatic injury. In view of the regional heterogeneity of NMDA receptors, the affinity of memantine for spinal cord NMDA receptors was also determined by studying displacement of [3H](+)-5-methyI-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imine (MK-801) to rat and human spinal cord homogenates. We found that memantine had an affinity for NMDA receptors in the spinal cord (Ki= 0.58 μM) that was significantly lower compared to that of the cerebral cortex (Ki= 0.23 μM) and that the affinity for NMDA receptors in human spinal cord was even lower. We conclude that in view of available data, memantine should not be chosen for clinical studies on neuroprotection in spinal cord injuries and that the lack of protective effect is most likely due to insufficient affinity of memantine for spinal cord NMDA receptors.Key words:memantine, neuroprotection,N-methyl-d-aspartate receptor, spinal cord inju

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.53

年代:1997

数据来源: MAL

摘要:

ABSTRACTWe evaluated in rats, the effect of moderate hypothermia (30–31°C) on extracellular levels of amino acids, with special emphasis on the excitatory amino acids (EAAs) glutamate and aspartate, lactate and pyruvate, after severe spinal cord compression. A laminectomy of Th7and Th8was made. A probe was inserted in a dorsal horn and microdialysis was performed for 1.5 h before and 4 h after applying severe compression for 5 min. Dialysate samples were collected at intervals of 10 min and analyzed by high-performance liquid chromatography. In normothermic (37.5°C) animals there was a several-fold rise of glutamate that peaked in the first 10 min fraction after trauma. Hypothermic animals showed a similar increase after trauma, which was statistically significant until 20 min after injury. The level of glutamate was significantly higher in hypothermie animals from 20 to 70 min after injury, compared with normothermic animals. Aspartate also showed a marked increase following injury. The peak concentration was similar for both groups, whereas recovery was delayed in hypothermic animals. There was no significant difference between the normothermic and hypothermic animals for arginine, taurine, alanine, glutamine, histadine, glycine, threonine, tyrosine, and asparagine. No significant effect of hypothermia on lactate or lactate/pyruvate was noted. However, the mean level of lactate tended to be lower and recovery was quicker in hypothermie animals. The results of the present study suggest that moderate hypothermia does not attenuate extracellular accumulation of EAAs or markedly improve energy metabolism in our model. Instead, our findings raise the possibility that moderate hypothermia prolongs the duration of glutamate receptor overactivation. Since hypothermia effectively attenuates glutamate release in CNS and spinal cord ischemia models our results suggest different mechanisms of extracellular accumulation of EAAs in ischemia and trauma.Key words:excitatory amino acids, glutamate, hypothermia, lactate, microdialysis, rat, spinal cord, tr

ISSN:0897-7151    

DOI:10.1089/neu.1997.14.63

年代:1997

数据来源: MAL