The extent of damage following spinal cord injury (SCI) can be reduced by various neuroprotective regimens that include maintaining levels of cyclic adenosine monophosphate (cyclic AMP), via administration of the phosphodiesterase 4 (PDE4) inhibitor Rolipram. The current study sought to determine the optimal neuroprotective dose, route and therapeutic window for Rolipram following contusive SCI in rat as well as its prominent PDE target and putative mechanism of protection. Rolipram or vehicle control (10% ethanol) was given subcutaneously (s.c.) daily for 2 wk post-injury (PI) after which the preservation of oligodendrocytes, neurons and central myelinated axons was stereologically assessed. Doses of 0.1 mg/kg to 1.0 mg/kg (given at 1 h PI) increased neuronal survival; 0.5 mg to 1.0 mg/kg protected oligodendrocytes and 1.0 mg/kg produced optimal preservation of central myelinated axons. Ethanol also demonstrated significant neuronal and oligo-protection; though the preservation provided was significantly less than Rolipram. Subsequent use of this optimal Rolipram dose, 1.0 mg/kg, via different routes (i.v., s.c. or oral, 1 h PI), demonstrated that i.v. administration produced the most significant and consistent cyto- and axo- protection, although all routes were effective. Examination of the therapeutic window for i.v. Rolipram (1.0 mg/kg), when initiated between 1 and 48 h after SCI, revealed maximal neuroprotection at 2 h post-SCI, although the protective efficacy of Rolipram could still be observed when administration was delayed for up to 48 h PI. Importantly, use of the optimal Rolipram regimen significantly improved locomotor function after SCI as measured by the BBB score. Lastly we show SCI-induced changes in PDE4A, B and D expression and phosphorylation as well as cytokine expression and immune cell infiltration. We demonstrate that Rolipram abrogates SCI-induced PDE4B1 and PDE4A5 production, PDE4A5 phosphorylation, MCP-1 expression and immune cell infiltration, while preventing post-injury reductions in IL-10. This work supports the use of Rolipram as an acute neuroprotectant following SCI and defines an optimal administration protocol and target for its therapeutic application.

Background: Hospitalized medical-surgical patients are at risk for adverse health outcomes due to immobility. Despite well-documented consequences, low mobility is prevalent. Local Problem: In a 547-bed hospital, medical-surgical patients were mobilized less frequently than expected. Physical therapists were inappropriately consulted 22% of the time for routine mobility of patients. A preimplementation survey of registered nurses indicated a lack of knowledge and confidence to safely mobilize patients. Methods: This quality improvement project implemented a nurse-led mobility program in an effort to increase early mobilization, reduce physical therapy referrals for routine mobility, and reduce the sequelae of immobility. Interventions: The Bedside Mobility Assessment Tool and standardized interventions were implemented on 5 medical-surgical units. Results: Postimplementation, nurse-led patient mobilizations increased by 40%, inappropriate physical therapy orders decreased 14%, and no significant change in patient falls or pressure injuries was noted. Conclusion: A nurse-led mobility program was effective in increasing safe, early mobilization of patients and improving the culture of mobility.

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Inducible nitric oxide synthase (iNOS) is a potent mediator of oxidative stress during neuroinflammation triggered by neurotrauma or neurodegeneration. We previously demonstrated that acute iNOS inhibition attenuated iNOS levels and promoted neuroprotection and functional recovery after spinal cord injury (SCI). The present study investigated the effects of chronic iNOS ablation after SCI using inos-null mice. iNOS−/− knockout and wild-type (WT) control mice underwent a moderate thoracic (T8) contusive SCI. Locomotor function was assessed weekly, using the Basso Mouse Scale (BMS), and at the endpoint (six weeks), by footprint analysis. At the endpoint, the volume of preserved white and gray matter, as well as the number of dorsal column axons and perilesional blood vessels rostral to the injury, were quantified. At weeks two and three after SCI, iNOS−/− mice exhibited a significant locomotor improvement compared to WT controls, although a sustained improvement was not observed during later weeks. At the endpoint, iNOS−/− mice showed significantly less preserved white and gray matter, as well as fewer dorsal column axons and perilesional blood vessels, compared to WT controls. While short-term antagonism of iNOS provides histological and functional benefits, its long-term ablation after SCI may be deleterious, blocking protective or reparative processes important for angiogenesis and tissue preservation.

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West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV in specific cell types and different regions of the brain modify immune protection is not fully understood. Here, we used a mouse ex vivo spinal cord slice culture (SCSC) and cerebellar slice culture (CSC) models to determine the innate immune responses specific to the CNS during WNV infection. Slices were prepared from the spinal cord and cerebellar tissue of 7–9-day-old mouse pups. Four-day-old SCSC or CSC were infected with 1 × 103 or 1 × 105 PFU of WNV, respectively. After 12 h exposure to WNV and 3 days post-infection in normal growth media, the pooled slice cultures were processed for total RNA extraction and for gene expression patterns using mouse Affymetrix arrays. The expression patterns of a number of genes were significantly altered between the mock- and WNV-treated groups, both in the CSCs and SCSCs. However, distinct differences were observed when CSC data were compared with SCSC. CSCs showed robust induction of interferons (IFNs), IFN-stimulated genes (ISGs), and regulatory factors. Some of the antiviral genes related to IFN were upregulated more than 25-fold in CSCs as compared to mock or SCSC. Though SCSCs had twice the number of dysregulated genes, as compared CSCs, they exhibited a much subdued IFN response. In addition, SCSCs showed astrogliosis and upregulation of astrocytic marker genes. In sum, our results suggest that early anti-inflammatory response to WNV infection in CSCs may be due to large population of distinct astrocytic cell types, and lack of those specialized astrocytes in SCSC may make spinal cord cells more susceptible to WNV damage. Further, the understanding of early intrinsic immune response events in WNV-infected ex vivo culture models could help develop potential therapies against WNV.

<p><strong>Objetivos: </strong>valorar la capacidad funcional de las personas mayores de 70 años según la escala <em>Short Physical Performance Battery</em> (sppb), para detectar incapacidad funcional precoz/prefragilidad y analizar la relación entre la puntuación del cuestionario y los niveles de calcio, albúmina y vitamina D. <strong>Métodos: </strong>estudio descriptivo transversal que incluyó a 77 pacientes mayores de 70 años que acudieron a consulta con su médico familiar por diversos motivos. Se les aplicó la escala<strong> </strong>sppb y se midieron valores de calcio, albúmina y vitamina D. Se consideró prefragilidad cuando la puntuación obtenida del spbb fue menor a 10. <strong>Resultados</strong>: la puntuación global del cuestionario fue de 7.75 ±2.72 puntos, lo cual colocó a 67.5% de los pacientes en prefragilidad. Se determinó una correlación entre la puntuación global y la puntuación por secciones; la velocidad al andar cuatro metros fue la sección con el mayor coeficiente de correlación con la puntuación total. Los niveles de vitamina D, calcio o albúmina no se correlacionaron con la puntuación del cuestionario<strong> </strong>sppb. <strong>Conclusiones: </strong>el porcentaje de pacientes prefrágiles por encima de 70 años fue muy alto. Se propone la utilización de la velocidad de la marcha (1.9 ±0.5 min) para aquellos médicos que tengan saturación de pacientes, ya que presentó la relación lineal directa más fuerte con la realización completa del cuestionario sppb.</p>

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