A single mild fluid percussion injury induces short-term behavioral and neuropathological changes in the Long-Evans rat: support for an animal model of concussion

Brain concussion is a serious public health concern and is associated with short-term cognitive impairments and behavioral disturbances that typically occur in the absence of significant brain damage. The current study addresses the need to better understand the effects of a mild lateral fluid percussion injury on rat behavior and neuropathology in an animal model of concussion. Male Long-Evans rats received either a single mild fluid percussion injury or a sham-injury, and either a short (24 h) or long (4 weeks) post-injury recovery period. After recovery, rats underwent a detailed behavioral analysis consisting of tests for rodent anxiety, cognition, social behavior, sensorimotor function, and depression-like behavior. After testing all rats were sacrificed and brains were examined immunohistochemically with markers for microglia/macrophage activation, reactive astrocytosis, and axonal injury. Injured rats (mean injury force: 1.20 ± .03 atm) displayed significant short-term cognitive impairments in the water maze and significantly more anxiolytic-like behavior in the elevated-plus maze compared to sham controls. Neuropathological analysis of the brains of injured rats showed an acute increase in reactive astrogliosis and activated microglia in cortex and evidence of axonal injury in the corpus callosum. There were no significant long-term effects on any behavioral or neuropathological measure 4 weeks after injury. These short-term behavioral and neuropathological changes are consistent with findings in human patients suffering a brain concussion, and provide further evidence for the use of a single mild lateral fluid percussion injury to study concussion in the rat.     

Extracellular proteases in epilepsy

During the last decade, multiple data have been obtained, pointing to an involvement of extracellular, including extrasynaptic, proteolysis in epilepsy pathogenesis. The most productive avenues of investigations have been analyses of seizure-evoked gene and protein expression patterns, both hypothesis-driven and unbiased (e.g., DNA microarrays), complemented by functional analyses in animal models, as well as expression and gene polymorphism studies carried out on human tissue In result, serine proteases (e.g., tPA, thrombin, trypsin-like proteases, etc.), metalloproteinases, natural protease inhibitors, as well as complement components, and reelin have been identified as a novel molecular system, emerging as a key factor in the development of epilepsy, in addition to well known contribution of ion channels and signal transduction pathways. The extracellular location of the enzymes makes them particularly attractive potential targets for future pharmacological therapeutic interventions.     

Effects of enoxaparin in the rat hippocampus following traumatic brain injury

Purpose of this study was to investigate the effects of low molecular weight heparin, enoxaparin, on different parameters of the hippocampal damage following traumatic brain injury (TBI) in the rat. TBI of moderate severity was performed over the left parietal cortex using the lateral fluid percussion brain injury model. Animals were s.c. injected with either enoxaparin (1 mg/kg) or vehicle 1, 7, 13, 19, 25, 31, 37, and 43 h after the TBI induction. Sham-operated, vehicle-treated animals were used as the control group. Rats were sacrificed 48 h after the induction of TBI. Hippocampi were processed for spectrophotometric measurements of the products of oxidative lipid damage, thiobarbituric acid-reactive substances (TBARS) levels, as well as the activities of antioxidant enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Moreover, the Western blotting analyses of the oxidized protein levels, expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro- and mature-interleukin-1β (pro-, and mature-IL-1β), and active caspase-3 were performed. COX-2 expressions were also explored by using immunohistochemistry. Glial fibrillary acidic protein immunochistochemistry was performed with the aim to assess the level of astrocytic activity. Fluoro-Jade B staining was used to identify the level and extent of hippocampal neuronal injury. TBI caused statistically significant increases of the hippocampal TBARS and oxidized protein levels as well as COX-2, pro-IL-1β, and active caspase-3 overexpressions, but it did not significantly affect the SOD and GSH-Px activities, the iNOS, and mature-IL-1β expression levels. TBI also induced hippocampal reactive astrocytosis and neurodegeneration. Enoxaparin significantly decreased the hippocampal TBARS and oxidized protein levels, COX-2 overexpression and reactive gliosis, but it did not influence the SOD and GSH-Px activities, pro-IL-1β and active caspase-3 overexpressions as well as neurodegeneration following TBI. These findings demonstrate that enoxaparin may reduce oxidative damage, inflammation and astrocytosis following TBI in the rat and could be a candidate drug for neuroprotective treatment of this injury.     

Chronic caloric restriction reduces tissue damage and improves spatial memory in a rat model of traumatic brain injury

Although it has been known for some time that chronic caloric or dietary restriction reduces the risk of neurodegenerative disorders and injury following ischemia, the possible role of chronic restriction in improving outcomes after traumatic brain injury (TBI) has not been previously studied. Therefore, 2‐month‐old male Sprague‐Dawley rats were divided into two dietary groups, an ad libitum fed group (AL) and a caloric‐restriction group (CR) that was provided with 70% of the food intake of AL rats (n = 10/group). After 4 months, a weight‐drop device (300 g) was used to produce a 2‐mm bilateral medial frontal cortex contusion following craniotomy. Additional animals in each dietary group (n = 10) were used as sham‐operated controls. The CR diet resulted in body weights that were reduced by 30% compared with AL controls. Not only did CR decrease the size of the cortical lesion after injury, there were marked improvements in spatial memory as measured by Morris water maze that included an increase in the number of animals successfully finding the platform as well as significantly reduced time to finding the hidden platform. Western analysis, used to examine the expression of proteins that play a role in neuronal survival, revealed significant increases in brain‐derived neurotrophic factor (BDNF) in the cortical region around the site of injury and in the hippocampus in CR rats after injury. These findings suggest that molecular mechanisms involved in cell survival may play a role in reducing tissue damage and improving cognition after TBI and that these mechanisms can be regulated by dietary interventions. © 2010 Wiley‐Liss, Inc.     

重型颅脑损伤36例临床分析

目的：总结重型颅脑损伤患者的救治方法及经验。方法：对我科收治的36例GCS评分在3～8分的重度颅脑损伤患者的资料进行回顾性分析。结果：36例患者手术治疗23例,非手术治疗13例;共存活26例,死亡10例。结论：重型颅脑损伤患者病情重,变化快而且并发症多,选择有效的治疗方法,保持内坏境稳定,可改善患者的预后,减少并发症及后遗症的发生,促进患者临床康复。     

Changes in concentration of cerebrospinal fluid components in patients with traumatic brain injury

Brain injury, like other central nervous system pathologies, causes changes in the composition of the cerebrospinal fluid (CSF). In this study, changes in the concentration of small molecules of the CSF, which are in the minimal micromolar concentration, were observed and monitored using high-resolution proton (NMR) spectroscopy. Twenty-two patients with isolated traumatic brain injuries (TBI) and 15 patients making up the control group were recruited for the study. CSF samples were collected by lumbar puncture from the lumbar subarachnoid space in the patients just before commencement of therapy and on the first, third, seventh and fourteenth days of therapy at the ICU. Forty-four signals of the NMR spectra and NO concentration of the CSF samples were analyzed. The analysis shows that the amino acid and organic acid concentrations change during the therapy and mostly are higher than in the control group. Significant differences in concentration of the analyzed CSF components between the TBI patients and the control group have been noted. The rate of the lactate to pyruvate conversion increased because the L/P ratio showed no significant differences between the TBI group and the control group, while the concentrations of both components were significantly higher in the TBI patients than in the control group. Citrulline, arginine and nitric oxide concentrations were the focus of the analysis. Citrulline concentration changes overlapped NO changes from 0 until 3rd day of therapy, while for the remaining days of observation the NO concentration stabilized at the control level, whereas citrulline concentration significantly decreased.     

Can diffusion tensor imaging predict motor power affection after moderate traumatic brain injury?

Objective

To determine whether commissural and projection fibers fractional anisotropy (FA) abnormalities can help in the prediction of long-term outcome of motor power affection after moderately severe traumatic brain injury (TBI).

Methods

MRI protocol included diffusion tensor imaging (DTI) and was performed for 32 patients with moderate TBI and 32 matched control subjects. Regions of interests were applied in the FA maps in the corpus callosum, internal capsules posterior limb, and cerebral peduncles. Results were compared in patients with motor power affection and patients without motor power affection to the control group.

Results

All patients had FA values lower than the control group with significance differences in the corpus callosum. Patient group with weakness had FA values lower than the control groups with significance differences in the posterior limb of the left internal capsules (p = 0.001) and left cerebral peduncles (p < 0.001). Significant differences were found when comparing the posterior limb of the left internal capsule (p = 0.002) and left cerebral peduncle (p = 0.022) to the right side in the weakness group.

Conclusion

FA values measured in the acute stage provided information about associated and projectional fibers disruptions, which have a prognostic value about motor power affection.