Alterations of resting-state regional and network-level neural function after acute spinal cord injury.

OBJECT: The purpose of this study was to investigate functional alterations of the brain in the early stage of spinal cord injury (SCI) and further investigate how these functional alterations relate to SCI patients' sensorimotor functions. METHODS: Twenty-five patients with SCI and 25 matched healthy controls underwent imaging by using resting-state functional magnetic resonance imaging (fMRI). The amplitude of low-frequency fluctuations (ALFF) were used to characterize regional neural function, and the seed-based functional connectivity (FC) was used to evaluate the functional integration of the brain network. RESULTS: Compared to healthy controls, patients with SCI showed decreased ALFF in the bilateral primary sensorimotor cortex, and increased ALFF in the bilateral cerebellum and right orbitofrontal cortex (OFC). The ALFF value in the left cerebellum was negatively correlated with the clinical total motor score in patients with SCI. Furthermore, SCI patients mainly showed decreased inter-hemispheric FC between the bilateral primary sensorimotor cortex, as well as increased intra-hemispheric FC within the motor network, including the primary sensorimotor cortex, premotor cortex, supplementary motor area (SMA), thalamus and cerebellum. Subsequent correlation analyses revealed that increased FC within the primary sensorimotor cortex, SMA, and cerebellum negatively correlated with the total American Spinal Cord Injury Association (ASIA) motor score. CONCLUSIONS: Our findings provide evidence that SCI can induce significant regional and network-level functional alterations in the early stage of the disease. We hypothesized these alterations may be an adaptive phenomenon following SCI, reflecting a compensatory mechanism during the early stage of SCI.

Brain sensorimotor system atrophy during the early stage of spinal cord injury in humans.

Spinal cord injury (SCI) usually leads to severe sensory and motor deficits below the spinal lesion. Previous animal models have shown significant atrophic changes in the neural sensorimotor system following SCI. However, specific anatomical changes in the human brain following SCI remain poorly understood. The purpose of the present study was to investigate structural changes during the early stage of SCI, and to investigate further the association between the structural changes and patients' sensorimotor functions. The study participants included 20 patients with SCI and 30 matched healthy controls. The mean period post-SCI was 8.9±2.7weeks (range 4-12weeks). Voxel-based morphometry was used to investigate the regions with gray and white matter volume changes. Compared to healthy controls, patients with SCI showed significant gray matter atrophy in the primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), and thalamus, as well as white matter atrophy in the corticospinal tracts at the level of the bilateral cerebral peduncles. In addition, gray matter volume in the primary motor cortex was positively correlated with the total American Spinal Injury Association motor score in patients with SCI. In conclusion, our findings suggest that SCI causes significant anatomical changes in the human sensorimotor system, and that these anatomical changes may occur in the early phase of SCI. Future treatments that aim to restore sensorimotor functions following SCI need to attend to these anatomical changes in the brain.

Interleukin-15 enhances T-cell responses by stimulation with dendritic cells

INTRODUCTION: Cytokines play important roles in regulating immune responses. Interleukin-2 (IL-2) has usually been used as an adjuvant to enhance antitumour immune responses. However, its crucial role in activation-induced cell death, inhibition of homeostatic proliferation of CD8+ memory T cells and its notable biological side effects impair its prospect of application. IL-15 has several similar functions to IL-2 and shows potential advantages over IL-2, and is being investigated to enhance antitumour dendritic cell (DC) vaccine strategies in our ongoing studies. OBJECTIVE: In this preliminary study, we evaluated the ability of IL-15, compared with IL-2, to act as an adjuvant to enhance T-cell responses activated by DCs in vitro. MATERIALS AND METHODS: Bone marrow-derived DCs (BMDCs) were pulsed with tumour antigens and used to stimulate lymphocyte responses in the presence of IL-15 or IL-2. The activated T lymphocytes were examined by flow cytometric analysis, and interferon-γ (IFN-γ) enzyme-linked immunospot and cytotoxicity assays. RESULTS: IL-15 was observed to activate lymphocytes with comparable phenotype characteristics of activated/memory CD8+ lymphocytes, compared with IL-2. Both in primary and secondary stimulation with DCs, when using IL-15 as an adjuvant, activated lymphocytes showed higher proportions of IFN-γ-secreting subsets. In secondary stimulation with BMDCs in the presence of IL-15, the activated lymphocytes showed a stronger cytotoxicity to antigen-specific tumour target cells. CONCLUSIONS: Our study suggested that IL-15 might be a prospective adjuvant for a DC vaccine strategy against cancers. The further observation that IL-15 acts as an adjuvant for an antitumour DC vaccine strategy is worth investigating (AU)

Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma.

MIG (monokine induced by interferon-gamma) is a CXC chemokine ligand (CXCL9) that can potently inhibit angiogenesis, and displays thymus-dependent antitumor effects. The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models. The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days. Tumor volume and survival time were evaluated after treatment. CD31 immunohistochemical staining in tumor tissues and alginate capsule models in vivo was used to evaluate angiogenesis. Induction of apoptosis and cytotoxic T-lymphocyte (CTL) activity were also assessed. The combination of pORF-MIG and low-dose cisplatin produced significant antitumor activity, with complete tumor regression in 4/10 of CT26 colon carcinomas and 3/10 of LL/2c lung carcinomas, low vascularity, in alginate capsules, apparently degraded tumor microvessel density, and increased induction of apoptotic and CTL activities compared with either treatment alone. This study suggests that the combination of pORF-MIG plus cisplatin augments the inhibition of angiogenesis and the induction of apoptosis or CTL activity, all of which enhance antitumor activity. These findings may prove useful in further explorations of the application of combinatorial approaches to the treatment of solid tumors.