Anesthesia for combined liver-thoracic transplantation

The combined transplantation of a thoracic organ and the liver is performed in patients with dual-organ failure in whom survival is not expected with single-organ transplantation alone. Although uncommonly performed, the number of combined liver-lung and liver-heart transplants is increasing. Anesthetic management of this complex procedure is challenging. Major blood loss, prolonged operation time, difficult weaning of cardiopulmonary bypass and coagulation disturbances are common. Despite the complexity of surgery, the outcome is comparable to single-organ transplant

Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities

Identifying patients at risk of traumatic brain injury (TBI) is important because research suggests prophylactic treatments to reduce risk of long-term sequelae. Blast pressure waves can cause TBI without penetrating wounds or blunt force trauma. Similarly, bullet impacts distant from the brain can produce pressure waves sufficient to cause mild to moderate TBI. The fluid percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the thigh produce pressure waves in the brain of 18-45 psi and measurable injury to neurons and neuroglia. Analyses of research in goats and epidemiological data from shooting events involving humans show high correlations (r > 0.9) between rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case study has documented epilepsy resulting from a pressure wave without the bullet directly hitting the brain. Taken together, these results support the hypothesis that bullet impacts distant from the brain produce pressure waves that travel to the brain and can retain sufficient magnitude to induce brain injury. The link to long-term sequelae could be investigated via epidemiological studies of patients who were gunshot in the chest to determine whether they experience elevated rates of epilepsy and other neurological sequelae

Mild concussive head injury results in increased brain substance P immunoreactivity

The document attached has been archived with permission from the Medimond International Proceedings Division. An external link to the publisher’s web site is included.The neuroinflammatory neuropeptide substance P (SP) has been implicated in oedema development following traumatic brain injury. Whether the neuropeptide plays a role in concussive head injury is unknown. Accordingly, we have used a newly developed model of mild head injury in rats to characterise the release of SP following concussive brain injury. Following brain trauma, there was no evidence of motor or cognitive deficits over the ensuing 3 weeks. Despite this, increased SP immunoreactivity was present in perivascular axons, some pyramidal neurones and astrocytes when compared to sham animals. Our findings suggest that concussive brain injury predisposes an individual to diffuse brain swelling, which may have implications in the management of sports related concussion.J.J. Donkin, I. Cernak, K.M. Rodgers and R. Vinkhttp://www.medimond.com/proceedings/moreinfo/20040912.ht

NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury

Exposure to repeated concussive traumatic brain injury (TBI) and to blast-induced TBI has been associated with the potential development of the neurodegenerative condition known as chronic traumatic encephalopathy (CTE). CTE is characterized by the accumulation of hyperphosphorylated tau protein, with the resultant tau tangles thought to initiate the cognitive and behavioral manifestations that appear as the condition progresses. However, the mechanisms linking concussive and blast TBI with tau hyperphosphorylation are unknown. Here we show that single moderate TBI, repeated concussive TBI and blast-induced mild TBI all result in hyperphosphorylation of tau via a substance P mediated mechanism. Post-injury administration of a substance P, NK1 receptor antagonist attenuated the injury-induced phosphorylation of tau by modulating the activity of several key kinases including Akt, ERK1/2 and JNK, and was associated with improvement in neurological outcome. We also demonstrate that inhibition of the TRPV1 mechanoreceptor, which is linked to substance P release, attenuated injury-associated tau hyperphosphorylation, but only when it was administered prior to injury. Our results demonstrate that TBI-mediated stimulation of brain mechanoreceptors is associated with substance P release and consequent tau hyperphosphorylation, with administration of an NK1 receptor antagonist attenuating tau phosphorylation and associated neurological deficits. NK1 antagonists may thus represent a pharmacological approach to attenuate the potential development of CTE following concussive and blast TBI.Frances Corrigan, Ibolja Cernak, Kelly McAteer, Sarah C. Hellewell, JefreyV. Rosenfeld ... et al

The next-generation ARC middleware

The Advanced Resource Connector (ARC) is a light-weight, non-intrusive, simple yet powerful Grid middleware capable of connecting highly heterogeneous computing and storage resources. ARC aims at providing general purpose, flexible, collaborative computing environments suitable for a range of uses, both in science and business. The server side offers the fundamental job execution management, information and data capabilities required for a Grid. Users are provided with an easy to install and use client which provides a basic toolbox for job- and data management. The KnowARC project developed the next-generation ARC middleware, implemented as Web Services with the aim of standard-compliant interoperability

Experimental traumatic brain injury

Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury

Shear Forces during Blast, Not Abrupt Changes in Pressure Alone, Generate Calcium Activity in Human Brain Cells

Blast-Induced Traumatic Brain Injury (bTBI) describes a spectrum of injuries caused by an explosive force that results in changes in brain function. The mechanism responsible for primary bTBI following a blast shockwave remains unknown. We have developed a pneumatic device that delivers shockwaves, similar to those known to induce bTBI, within a chamber optimal for fluorescence microscopy. Abrupt changes in pressure can be created with and without the presence of shear forces at the surface of cells. In primary cultures of human central nervous system cells, the cellular calcium response to shockwaves alone was negligible. Even when the applied pressure reached 15 atm, there was no damage or excitation, unless concomitant shear forces, peaking between 0.3 to 0.7 Pa, were present at the cell surface. The probability of cellular injury in response to a shockwave was low and cell survival was unaffected 20 hours after shockwave exposure

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI

Models of Traumatic Cerebellar Injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective