Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4

AbstractMast cells (MCs) are found abundantly in the central nervous system and play a complex role in neuroinflammatory diseases such as multiple sclerosis and stroke. In the present study, we show that MC-deficient KitW-sh/W-sh mice display significantly increased astrogliosis and T cell infiltration as well as significantly reduced functional recovery after spinal cord injury compared to wildtype mice. In addition, MC-deficient mice show significantly increased levels of MCP-1, TNF-α, IL-10 and IL-13 protein levels in the spinal cord. Mice deficient in mouse mast cell protease 4 (mMCP4), an MC-specific chymase, also showed increased MCP-1, IL-6 and IL-13 protein levels in spinal cord samples and a decreased functional outcome after spinal cord injury. A degradation assay using supernatant from MCs derived from either mMCP4−/− mice or controls revealed that mMCP4 cleaves MCP-1, IL-6, and IL-13 suggesting a protective role for MC proteases in neuroinflammation. These data show for the first time that MCs may be protective after spinal cord injury and that they may reduce CNS damage by degrading inflammation-associated cytokines via the MC-specific chymase mMCP4

Associations Between Mobile Health Technology Use and Self-rated Quality of Life: A Cross-sectional Study on Older Adults with Cognitive Impairment

Background: Quality of life (QoL) is affected even at early stages in older adults with cognitive impairment. The use of mobile health (mHealth) technology can offer support in daily life and improve the physical and mental health of older adults. However, a clarification of how mHealth technology can be used to support the QoL of older adults with cognitive impairment is needed. Objective: To investigate factors affecting mHealth technology use in relation to self-rated QoL among older adults with cognitive impairment. Methods: A cross-sectional research design was used to analyse mHealth technology use and QoL in 1082 older participants. Baseline data were used from a multi-centred randomised controlled trial including QoL, measured by the Quality of Life in Alzheimer’s Disease (QoL-AD) Scale, as the outcome variable. Data were analysed using logistic regression models. Results: Having moderately or high technical skills in using mHealth technology and using the internet via mHealth technology on a daily or weekly basis was associated with good to excellent QoL in older adults with cognitive impairment. Conclusions: The variation in technical skills and internet use among the participants can be interpreted as an obstacle for mHealth technology to support QoL

Interleukin-25 is detrimental for recovery after spinal cord injury in mice

BACKGROUND: The cytokine, interleukin (IL)-25, is thought to be critically involved in inducing a type 2 immune response which may contribute to regeneration after central nervous system (CNS) trauma. We investigated whether applying recombinant IL-25, locally or systemically, in a mouse model of spinal cord injury (SCI) improves functional and histological recovery. FINDINGS: Repeated systemic administration of IL-25 did not influence functional recovery following SCI. In contrast, a single local administration of IL-25 significantly worsened locomotor outcome, which was evident from a decreased Basso mouse scale (BMS) score compared with phosphate-buffered saline (PBS)-treated controls. This was accompanied by a significant increase in lesion size, demyelination, and T helper cell infiltration. CONCLUSIONS: These data show for the first time that IL-25 is either ineffective when applied systemically or detrimental to spinal cord recovery when applied locally. Our findings question the potential neuroprotective role of IL-25 following CNS trauma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0566-y) contains supplementary material, which is available to authorized users

In Vitro and In Vivo Neuronal Electrotaxis: A Potential Mechanism for Restoration?

Electrical brain stimulation used to treat a variety of neurological and psychiatric diseases is entering a new period. The technique is well established and the potential complications are well known and generally manageable. Recent studies demonstrated that electrical fields (EFs) can enhance neuroplasticity-related processes. EFs applied in the physiological range induce migration of different neural cell types from different species in vitro. There are some evidences that also the speed and directedness of cell migration are enhanced by EFs. However, it is still unclear how electrical signals from the extracellular space are translated into intracellular actions resulting in the so-called electrotaxis phenomenon. Here, we aim to provide a comprehensive review of the data on responses of cells to electrical stimulation and the relation to functional recovery

Additional file 1: of Interleukin-25 is detrimental for recovery after spinal cord injury in mice

Supplementary Materials. Detailed description of materials and methods used throghout the manuscript, provided as supplementary information. (DOCX 35 kb

Additional file 2: Figure S1. of Interleukin-25 is detrimental for recovery after spinal cord injury in mice

IL-25 has no effect on mature oligodendrocyte, astrocyte, microglia, or primary neuron cell viability. (A) MO3.13 cells were differentiated to mature oligodendrocytes using PMA for 72 h and were treated for 48 h with selected concentrations of IL-25. (B, C) The astrocytic and microglial cell lines (CCF and BV2, respectively) were treated for 48 h with selected concentrations of IL-25. (D) Primary neurons were incubated with selected concentrations of IL-25 for 48 h in the presence or absence of B27. B27 deprivation induced a decreased cell viability, but IL-25 treatment had no effect on this. The selected concentrations of IL-25 used for all cell types were 5 ng/ml, 50 ng/ml, 500 ng/ml, and 1 μg/ml. Cell survival was measured using an MTT assay, and values are expressed as percentage of the control. (A-D) There was no significant effect observed on cell viability in all cell types tested. Data represent mean ± SEM of one representative experiment (from two to three independent experiments) ***p < 0.001. (PDF 316 kb

Cell-based delivery of interleukin-13 directs alternative activation of macrophages resulting in improved functional outcome after spinal cord injury

The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%. Further histological analyses in CX(3)CR1(EGFP/+) CCR2(RFP/+) transgenic mice indicated that MSC/IL-13 significantly decrease the number of resident microglia and increase the number of alternatively activated macrophages. In addition, the number of macrophage-axon contacts in MSC/IL-13-treated mice was decreased by 50%, suggesting a reduction in axonal dieback. Our data provide evidence that transplantation of MSC/IL-13 leads to improved functional and histopathological recovery in a mouse model of SCI

The Effects of the Digital Platform Support Monitoring and Reminder Technology for Mild Dementia (SMART4MD) for People With Mild Cognitive Impairment and Their Informal Carers : Protocol for a Pilot Randomized Controlled Trial

Background: Many countries are witnessing a trend of growth in the number and proportion of older adults within the total population. In Europe, population aging has had and will continue to have major social and economic consequences. This is a fundamentally positive development where the added life span is of great benefit for both the individual and the society. Yet, the risk for the individual to contract noncommunicable diseases and disability increases with age. This may adversely affect the individual's ability to live his or her life in the way that is desired. Cognitive conditions constitute a group of chronic diseases that predominantly affects older people. Recent technology advancements can help support the day-to-day living activities at home for people with cognitive impairments. Objective: A digital platform (Support Monitoring and Reminder for Mild Dementia; SMART4MD) is created to improve or maintain the quality of life for people with mild cognitive impairment (PwMCI) and their carers. The platform will provide reminders, information, and memory support in everyday life, with the purpose of giving structure and lowering stress. In the trial, we will include participants with a diagnosed neurocognitive disorder as well as persons with an undiagnosed subjective memory problem and cognitive impairment, that is, 20 to 28 points on the Mini-Mental State Examination. Methods: A pragmatic, multicenter RCT is being conducted in Spain, Sweden, and Belgium. The targets for recruitment are 1200 dyads-split into an intervention group and a control group that are in usual care. Intervention group participants will be provided with a data-enabled computer tablet with the SMART4MD app. Its core functionalities, intended to be used daily at home, are based on reminders, cognitive supporting activities, and sharing health information. Results: Inclusion of participants started in December 2017, and recruitment is expected to end in February 2019. Furthermore, there will be 3 follow-up visits at 6, 12, and 18 months after the baseline visit. Conclusions: This RCT is expected to offer benefits at several levels including in-depth knowledge of the possibilities of introducing a holistic multilayered information and communication technology solution for this group. SMART4MD has been developed in a process involving the structured participation of PwMCI, their informal carers, and clinicians. The adoption of SMART4MD faces the challenge of this age group's relative unfamiliarity with digital devices and services. However, this challenge can also be an opportunity for developing a digital device tailored to a group at risk of digital exclusion. This research responds to the wider call for the development of digital devices which are accessible and affordable to older people and this full scale RCT can hopefully serve as a model for further studies in this field.open access</p