CD4 T cells mediate axonal damage and spinal cord motor neuron apoptosis in murine p0106-125-induced experimental autoimmune neuritis

The pathogenesis of inflammatory autoimmune diseases of the peripheral nervous system, leading to demyelination and/or axonal damage, remains incompletely understood. In particular, it is controversial regarding the extent to which (i) autoimmune-mediated destruction of peripheral nerves results in secondary damage of the central nervous system, and (ii) CD4 and CD8 T cells contribute to disease. To address these issues, we applied the murine model of P0(106-125)-induced experimental autoimmune neuritis. Immunization of C57BL/6 mice with P0(106-125) resulted in severe axonal damage and mild demyelination. Importantly, these mice developed a "dying-back" axonopathy with apoptosis of a large fraction of neurons in the anterior horn of the lumbar and thoracic spinal cord and a progressive neurogenic muscular atrophy. T cell-depletion experiments identified CD4, but not CD8, T cells as important mediators of experimental autoimmune neuritis. CD4 T cells represented the major cellular source of antigen-specific interferon-gamma and interleukin-17 production, regulated the number of tumor necrosis factor-positive and inducible nitric oxide synthase-positive macrophages in the diseased sciatic nerve, and mediated axonal damage and subsequent neuronal apoptosis and neurogenic muscular atrophy. In contrast, the demyelination of peripheral nerves was only slightly ameliorated in CD4 T cell-depleted mice. In conclusion, P0(106-125)-induced experimental autoimmune neuritis is a CD4 T cell-mediated autoimmune disease that affects both the peripheral and central nervous systems.     

Responses of rat nucleus submedius neurons to enkephalins applied with micropressure

The purpose of this study was to determine what effects leucine-enkephalin and d-Ala²-d-Leu⁵-enkephalin have on both the background and naturally evoked activity of thalamic nucleus submedius neurons responsive to mechanical cutaneous stimulation. Thirty-five neurons in the nucleus submedius were fully characterized during single-unit extracellular recordings as nociceptive, low-threshold mechanoreceptive (LTM) or unresponsive. Micropressure was used to apply the opioids. Eighteen neurons were inhibited; 13 of these were nociceptive and one was LTM. Six units were activated; two of these were nociceptive and three were LTM. The remaining 11 units were unaffected. Opioid responses were tested for antagonism by naloxone in 12 neurons; eight of these responses were antagonized by naloxone. Statistical analyses indicated that the effects of enkephalins on nociceptive neurons were selective for neuronal modality. The opioids also altered the response of some nociceptive neurons to receptive field stimulation. The presence of nociceptive neurons in the nucleus submedius that are selevtively inhibited by opioids provides additional support for the involvement of submedius neurons in nociception. The results of this study suggest that this involvement is more than merely transmission of nociceptive input, since the opioids may be selectively modulating the type of information that is transmitted to the cortex.     

The neural network for tool-related cognition: An activation likelihood estimation meta-analysis of 70 neuroimaging contrasts

ABSTRACT

The ability to recognize and use a variety of tools is an intriguing human cognitive function. Multiple neuroimaging studies have investigated neural activations with various types of tool-related tasks. In the present paper, we reviewed tool-related neural activations reported in 70 contrasts from 56 neuroimaging studies and performed a series of activation likelihood estimation (ALE) meta-analyses to identify tool-related cortical circuits dedicated either to general tool knowledge or to task-specific processes. The results indicate the following: (a) Common, task-general processing regions for tools are located in the left inferior parietal lobule (IPL) and ventral premotor cortex; and (b) task-specific regions are located in superior parietal lobule (SPL) and dorsal premotor area for imagining/executing actions with tools and in bilateral occipito-temporal cortex for recognizing/naming tools. The roles of these regions in task-general and task-specific activities are discussed with reference to evidence from neuropsychology, experimental psychology and other neuroimaging studies.     

Distally locked stems in revision hip arthroplasties: surgical technique and indications

In case of severe femoral bone loss, cementless revision hip arthroplasties require a stable initial distal fixation that does not compromise a subsequent bone reconstruction. The locking mechanism provides initially reliable fixation, especially if bone loss has spread to the distal femoral isthmus or when an extended trochanteric osteotomy (femorotomy) is indicated. Locking stems can be used in all types of femoral revision, but this type of implant can be especially useful in case of diaphysial damage (beyond the isthmus) which makes fixation of a long cemented or non-cemented stem uncertain; in case of septic revisions which need a careful femoral cleaning; in case of peri-prosthetic fractures or if surgical complications (false route, fracture, perforations) occur that impair fixation of a cemented stem or one that is not of standard length. All approaches may be used, but the need for access to the femur dictates choice of the antero-lateral and especially the postero-lateral route. The choice of diameter is guided by “press-fit” beyond the femorotomy, thus minimizing the stresses that will consequently be exerted on the locking system. The size will be chosen also to optimize the contact between residual bone and prosthetic surface treatment in the metaphysial proximal and diaphysial regions. The stem must be locked depending a few technical requirements. The position of the stem will be chosen regarding limb length (height) and joint stability (anteversion). The quality of femorotomy closure is evaluated by achieving broad contact between the flap and the proximal part of the stem. When the medial part of the femur relative to the flap remains distant from the stem, a “counter-femorotomy” of medial cortical bone made at a different level should be performed to optimize contact. These implants simplify femoral revisions by facilitating femorotomy in complex situations. This method offers constant bone reconstruction without significant bone grafting and durable fixation if locking mechanism is added to an adjusted implant in contact with native bone, limiting short-and long-term stresses on it.     

Depression with psychotic features in a child with SLE: successful therapy with psychotropic medications—case report

Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease of unknown etiology, which affects multiple organ systems, including the central nervous system (CNS). Neuropsychiatric manifestations are seen in 13–75 % of all SLE patients, with equal frequency in children and adults. Despite a high prevalence of psychiatric manifestations, there is no consensus on the proper treatment of such cases. We report here a case of an 11-year-old girl diagnosed with a severe depressive episode with psychotic features, treated successfully with risperidone and sertraline as an adjunct to immunosuppressive therapy.