Trauma In Animal Model Research Articles

Efficacy of epothilones in central nervous system trauma treatment: what has age got to do with it?

Central nervous system injury, specifically traumatic brain and spinal cord injury, can have significant long lasting effects. There are no comprehensive treatments to combat the injury and sequalae of events that occurring following a central nervous system trauma. Herein we discuss the potential for the epothilone family of microtubule stabilizing agents to improve outcomes following experimentally induced trauma. These drugs, which are able to cross the blood-brain barrier, may hold great promise for the treatment of central nervous system trauma and the current literature presents the extensive range of beneficial effects these drugs may have following trauma in animal models. Importantly, the effect of the epothilones can vary and our most recent contributions to this field indicate that the efficacy of epothilones following traumatic brain injury is dependent upon the age of the animals. Therefore, we present a case for a greater emphasis to be placed upon age when using an intervention aimed at neural regeneration and highlight the importance of tailoring the therapeutic regime in the clinic to the age of the patient to promote improved patient outcomes.

Abdominal Wall Reconstruction after Flap Surgery and the Effect on the Immune System.

Background The aim of our study was to investigate the impact of abdominal wall reconstruction surgery on tissue anatomy and to explore how flap surgery influences the patient's immune status. Methods Experimental abdominal wall defects were created in 8 Sus scrofa (swine) animal models. The animals were divided into two groups: 4 swine were euthanized one month after surgery for the biopsies retrieval purpose and the other 4 swine were kept alive and the collection of blood samples has been done 6 months after surgery. In order to evaluate the relative gene expression in operated-on animal cohorts we compared them with samples from 4 healthy swine used as controls. Results The inflammatory process was present in all types of repairs. Collagen I deposition was higher in the flap repairs. The expression level for the genes related to immune response after 6 months from surgery was relatively similar to the control group except minor alteration registered in the case of two swine models. Conclusion Our findings indicate a less pronounced proinflammatory response to surgical trauma in animal models after flap surgery. The postoperative levels of the inflammatory cytokines did not show significant differences after abdominal wall reconstruction using flap surgery.

Editorial: Auditory Efferent System: New Insights from Cortex to Cochlea.

Editorial: Auditory Efferent System: New Insights from Cortex to Cochlea.

Increased expression of ferritin in cerebral cortex after human traumatic brain injury

Despite numerous researches and improvements in the past few years, the precise mechanisms underlying secondary brain injury after trauma remain obscure. Iron is essential for almost all types of cells, including nerve cells. However, excess of iron has been proved to contribute to the brain injury following trauma in animal models. As a key iron-handling protein in the brain, ferritin might be involved in iron-induced pathophysiological process of various brain disorders. Therefore, the current study was aimed to investigate the expression of ferritin in the human contused brain. Nineteen contused brain samples were obtained from 19 patients undergoing surgery for brain contusions 3 h-17 d after trauma, and three normal temporal pole samples from 3 patients with petroclival meningioma were collected as controls. Expression of ferritin-H-chain was measured by quantitative real-time polymerase chain reaction (PCR), western blot and immunohistochemistry, respectively. Perl's reaction was taken for iron staining. The results showed that human traumatic brain injury (TBI) could up-regulate ferritin-H-chain in pericontusional cortex. A marked increase of ferritin was detected in the early group (≤12 h), and remained elevated for a long time till after 48 h post-injury. The location of ferritin-H-chain was found mainly at the neuron-like cells and seldom at glia-like cells. Perl's reaction showed that most of the iron-positive cells were glia-like cells. These findings suggested that iron and ferritin might be involved in the secondary brain injury and could be therapeutic targets for patients with TBI.

Increased CD133(+) cell infiltration in the rat brain following fluid percussion injury.

The prominin-1/CD133 epitope is expressed in undifferentiated cells. Studies have reported that craniocerebral trauma in animal models of fluid percussion injury induces production of a specific stem cell subgroup. It has been hypothesized that fluid percussion injury induces CD133+ cell infiltration in the brain tissue. The present study established a traumatic brain injury model through fluid percussion injury. Immunohistochemical staining showed significantly increased CD133 antigen expression in the rat brain following injury. CD133+ cells were mainly distributed in hippocampal CA1–3 regions, as well as the dentate gyrus and hilus, of the lesioned hemisphere. Occasional cells were also detected in the cortex. In addition, reverse transcription-PCR revealed that no change in CD133 mRNA expression in injured brain tissue. These results suggested that fluid percussion injury induced CD133 antigen expression in the brain tissues as a result of conformational epitope changes, but not transcriptional expression.

Sa1458 Clinical Impact of EUS-Guided Fine Needle Aspiration Biopsy in the Diagnosis of Lymphoma

Sa1458 Clinical Impact of EUS-Guided Fine Needle Aspiration Biopsy in the Diagnosis of Lymphoma

Intratympanic treatment of acute acoustic trauma with a cell-permeable JNK ligand: a prospective randomized phase I/II study

Objectives. Intratympanic administration of a cell-permeable JNK ligand has been shown to prevent hearing loss after acute acoustic trauma in animal models. Conclusions. Functional and morphological analysis of the treated ears revealed that AM-111 had an excellent otoprotective effect, even when administered hours after the noise exposure. Blocking the signal pathway with D-JNKI-1 is therefore a promising way to protect the morphological integrity and physiological function of the inner ear in various conditions involving acute sensorineural hearing loss. Subjects and methods. For the first application of AM-111 in humans, we organized a clinical phase I/II trial in patients with acute acoustic trauma after exposure to firecrackers in Berlin and Munich on New Year's Eve 2005/2006. We randomly selected 11 patients for intratympanic treatment with AM-111 at a concentration of 0.4 mg/ml or 2 mg/ml within 24 h after noise exposure. Pure tone audiometry and otoacoustic emissions were assessed before treatment and on days 3 and 30 thereafter. Results. Based on clinical experience and on a calculation using an empirically derived exponential hearing recovery function AM-111 seems to have had a therapeutic effect. A total of 13 adverse events were reported in 5 study participants. None of the adverse events were serious or severe.

Adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 inhibits the formation of heterotopic ossification in animal model

The heterotopic ossification of muscles, tendons, and ligaments is a common problem faced by orthopaedic surgeons. Runx2/Cbfa1 plays an essential role during the osteoblast differentiation and is considered as a molecular switch in osteoblast biology. RNA interference technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. In this study, we investigated the effect of Runx2/Cbfa1-specific siRNA on osteoblast differentiation and mineralization in osteoblastic cells, and then constructed adenovirus containing siRNA against Runx2/Cbfa1 (Ad-Runx2-siRNA) to inhibit the formation of heterotopic ossification induced by BMP4, demineralized bone matrix, and trauma in animal model. Our results showed that the Runx2/Cbfa1-specific siRNA could inhibit the expression of Runx2/Cbfa1 at the level of mRNA and protein. Analysis of the expression of osteoblast maturation genes including type I collagen, osteopontin, bone sialoprotein, and osteocalcin, alkaline phosphatase activity, and matrix mineralization (von kossa) revealed that osteoblast differentiation was inhibited in cultured primary mouse osteoblasts transduced with Ad-Runx2-siRNA. Furthermore, adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 could inhibit the formation of heterotopic ossification induced by BMP4, demineralized bone matrix, and trauma in animal model. It is likely that the inhibition of Runx2/Cbfa1 by RNAi could be developed as a powerful approach to prevent or treat heterotopic ossification.

Efficacy of the Antioxidant N-acetylcysteine (NAC) in Protecting Ears Exposed to Loud Music

Antioxidants have been reported to be effective in reducing acoustic trauma in animal models but have not been studied in humans. In this study, the antioxidant N-acetylcysteine (NAC) was evaluated to determine if it would reduce temporary changes in auditory function as a result of exposure to loud music in humans. Pure-tone thresholds and distortion product otoacoustic emissions (DPOAEs) were collected in 31 normal-hearing participants, using a randomized, double-blind, placebo-controlled design, before and after two hours of live music in a nightclub. Using repeated measures analysis of variance, no statistically significant differences were found between participants who received NAC versus a placebo for any of the outcome measures. Across all subjects, the largest pure-tone threshold shift occurred at 4 kHz. DPOAE measures were characterized by reductions in amplitude and a trend for shorter group delay values. When the 3 and 4 kHz data were examined by imposing specific criteria of greater than 2 dB DPOAE amplitude reductions and 10 dB or greater pure-tone threshold shifts, DPOAE reductions occurred more often at 3 kHz, and pure-tone shifts occurred more often at 4 kHz.

Influence of steroids on oxidant generation in activated human granulocytes and mononuclear leukocytes.

Steroids, in particular, 17beta-estradiol (E(2)), have been reported to improve the response to trauma in animal models. In these models, the leukocyte plays a critical role in the inflammatory cascade. We examined the affects of E(2), hydrocortisone (H), progesterone (P(4)), and E(2) with P(4) on oxidant production in human granulocytes (PMNs) and mononuclear leukocytes (MNCs). Each cell type was loaded with 2,7-dichlorodihydrofluorescein and then simultaneously activated with human cytokines (tumor necrosis factor alpha, interleukin-1beta, and interferon gamma) and hemoglobin and inhibited with and without equimolar concentrations of each steroid treatment or nitric oxide (NO) synthesis inhibitors. After incubations of 1 or 5 h, intracellular oxidants were quantified by flow cytometry. Activation by cytokines combined with hemoglobin, resulted in a 450-575% increase in oxidant production that was synergistically greater than the sum of either component alone. Pharmacological levels of E(2) decreased oxidants in MNCs at 1 h. In contrast at 5 h, H decreased oxidants more than E(2). The addition of P(4) to E(2) concentrations almost eliminated oxidants from 1 h-activated MNCs. None of the steroids significantly reduced oxidants in PMNs, suggesting that the E(2) effect on MNCs was not caused by its nonreceptor-mediated antioxidant properties. Because L-NMMA inhibited at least 55% of the total oxidants, part of E(2) dampening effects would be attributed to NO. These results suggest that steroid-attenuated MNC-derived NO may reduce autocrine and paracrine effects on inflammation if appropriate doses of steroids are given soon after injury.

Plasma fibronectin: relevance for anesthesiology and intensive care.

Plasma fibronectin has been postulated to be an essential mediator of normal reticuloendothelial system (RES) function. The acute depletion of fibronectin is thought to impair RES function, whereas its repletion in states of deficiency has been reported to improve RES function. In vitro studies have documented fibronectin's ability to bind to some nonbacterial microaggregates and to promote the phagocytosis of bound targets by the RES. These properties may, however, be influenced by the in vivo milieu. There is substantial evidence for a parallelism between RES function and plasma fibronectin levels following blunt trauma in animal models; however, this association is not seen in experimentally induced intravascular coagulation, acute inflammation, and sepsis. Clinically, subnormal fibronectin levels are clearly associated with the triad of intravascular coagulation, organ failure and sepsis. Fibronectin is, however, not the only plasma protein reduced in these patients, nor is it an outstanding predictor of such complications. The therapeutic efficacy of fibronectin administration remains controversial. Whereas initial reports suggested therapeutic benefits of fibronectin-enriched cryoprecipitates, subsequent studies have produced negative results. Prospective, randomized, controlled clinical trials with purified fibronectin are needed before fibronectin should be recommended as an adjunct to the established principles of intensive care.