TGFβ signaling is associated with changes in inflammatory gene expression and perineuronal net degradation around inhibitory neurons following various neurological insults.

Brain damage due to stroke or traumatic brain injury (TBI), both leading causes of serious long-term disability, often leads to the development of epilepsy. Patients who develop post-injury epilepsy tend to have poor functional outcomes. Emerging evidence highlights a potential role for blood-brain barrier (BBB) dysfunction in the development of post-injury epilepsy. However, common mechanisms underlying the pathological hyperexcitability are largely unknown. Here, we show that comparative transcriptome analyses predict remodeling of extracellular matrix (ECM) as a common response to different types of injuries. ECM-related transcriptional changes were induced by the serum protein albumin via TGFβ signaling in primary astrocytes. In accordance with transcriptional responses, we found persistent degradation of protective ECM structures called perineuronal nets (PNNs) around fast-spiking inhibitory interneurons, in a rat model of TBI as well as in brains of human epileptic patients. Exposure of a naïve brain to albumin was sufficient to induce the transcriptional and translational upregulation of molecules related to ECM remodeling and the persistent breakdown of PNNs around fast-spiking inhibitory interneurons, which was contingent on TGFβ signaling activation. Our findings provide insights on how albumin extravasation that occurs upon BBB dysfunction in various brain injuries can predispose neural circuitry to the development of chronic inhibition deficits

TGFβ signaling is associated with changes in inflammatory gene expression and perineuronal net degradation around inhibitory neurons following various neurological insults

Brain damage due to stroke or traumatic brain injury (TBI), both leading causes of serious long-term disability, often leads to the development of epilepsy. Patients who develop post-injury epilepsy tend to have poor functional outcomes. Emerging evidence highlights a potential role for blood- brain barrier (BBB) dysfunction in the development of post-injury epilepsy. However, common mechanisms underlying the pathological hyperexcitability are largely unknown. Here, we show that comparative transcriptome analyses predict remodeling of extracellular matrix (ECM) as a common response to different types of injuries. ECM-related transcriptional changes were induced by the serum protein albumin via TGFβ signaling in primary astrocytes. In accordance with transcriptional responses, we found persistent degradation of protective ECM structures called perineuronal nets (PNNs) around fast-spiking inhibitory interneurons, in a rat model of TBI as well as in brains of human epileptic patients. Exposure of a naïve brain to albumin was sufficient to induce the transcriptional and translational upregulation of molecules related to ECM remodeling and the persistent breakdown of PNNs around fast-spiking inhibitory interneurons, which was contingent on TGFβ signaling activation. Our findings provide insights on how albumin extravasation that occurs upon BBB dysfunction in various brain injuries can predispose neural circuitry to the development of chronic inhibition deficits

EMERGENCE OF AUTOCHTHONOUS CHIKUNGUNYA IN PALM BEACH COUNTY, FLORIDA

Background. On July 7, 2014 Florida Department of Health Palm Beach County received a report of a patient that had symptoms consistent with chikungunya fever but denied history of travel outside the USA. On July 17, 2014 the CDC declared this as one of the first chikungunya virus disease cases acquired in the continental United States. Methods. Cases were identified through active and passive surveillance. A field investigation was conducted. All homes within 100 meters of the autochthonous case-patient were visited, residents were interviewed, symptomatic or asymptomatic persons were identified. Risk factors were evaluated; blood samples were obtained from willing participants. An environmental assessment was conducted. Results. By October 4, 2014, through active surveillance four autochthonous cases with chikungunya virus (CHIKV) infection were identified in Palm Beach County, FL. 78 households were visited. No additional symptomatic or asymptomatic persons were identified. A total of eight asymptomatic individuals associated with the first case were tested and none were positive for CHIKV. The field teams identified mosquito-breeding sites on all of the interviewed properties and drained and covered the stagnant water. None of the potential breeding sites contained larvae currently. No CHIKV infections were found to be associated to any of the autochthonous cases. Conclusions. There was no clear epidemiological link established through geo-spatial relationships during incubation and infective periods among imported and/or autochthonous case-patients. Isolation of case-patients during the viremic phase likely diminished transmission risk among household members and local community members. Public Health Implication. If local transmission continues, there is a risk that the virus will thrive and become endemic in these new areas

Finding degrees of separation: Experimental approaches for astroglial and oligodendroglial cell isolation and genetic targeting

The study of CNS glial cell function requires experimental methods to detect, purify, and manipulate each cell population with fidelity and specificity. With the identification and cloning of cell- and stage-specific markers, glial cell analysis techniques have grown beyond physical methods of tissue dissociation and cell culture, and become highly specific with immunoselection of cell cultures in vitro and genetic targeting in vivo. The unique plasticity of glial cells offers the potential for cell replacement therapies in neurological disease that utilize neural cells derived from transplanted neural stem and progenitor cells. In this mini-review, we outline general physical and genetic approaches for macroglial cell generation. We summarize cell culture methods to obtain astrocytes and oligodendrocytes and their precursors, from developing and adult tissue, as well as approaches to obtain human neural progenitor cells through the establishment of stem cells. We discuss popular targeting rodent strains designed for cell-specific detection, selection and manipulation of neuroglial cell progenitors and their committed progeny. Based on shared markers between astrocytes and stem cells, we discuss genetically modified mouse strains with overlapping expression, and highlight SOX-expressing strains available for targeting of stem and progenitor cell populations. We also include recently established mouse strains for detection, and tag-assisted RNA and miRNA analysis. This discussion aims to provide a brief overview of the rapidly expanding collection of experimental approaches and genetic resources for the isolation and targeting of macroglial cells, their sources, progeny and gene products to facilitate our understanding of their properties and potential application in pathology

Olfactomedin 2: Expression in the Eye and Interaction with Other Olfactomedin Domain–Containing Proteins

This study reports the expression of olfactomedin 2 during the course of mouse and rat eye development and its interaction with other olfactomedin family members

HIGHER BODY MASS INDEX IS ASSOCIATED WITH WORSE CLINICAL OUTCOMES OF HYLAN G-F 20 INJECTIONS IN THE SHOULDER AND HIP JOINTS OF PATIENTS WITH OSTEOARTHRITIS

Background. Intra-articular hyaluronan injections are approved by the Food and Drug Administration for the management of knee osteoarthritis. The effectiveness and safety of use of viscosupplementation in other joints are still unclear, and no evidence-based criteria are established to screen the patients for such treatment. Research Question. The effectiveness and safety of the use of viscosupplementation for the management of osteoarthritis of the shoulder and hip. Protocol/Methods. In a case series study, we retrospectively reviewed the charts of the 26 patients undergoing fluoroscopically-guided intra-articular Hylan G-F 20 injections for the management of osteoarthritis of the shoulder (21 injections) and hip (31 injections). Age, gender, body mass index, number of co-morbidities, use of opiates, severity, and location of osteoarthritis were assessed as possible prognostic factors. The number of months of pain relief and the degree of symptomatic improvement were considered outcomes for this study. Results. Our analysis showed that the injections provide effective pain relief for up to 4 months in 72 approximately half of the patients with a few patients experiencing pain relief during the whole observation period of 24-30 months. No adverse events were reported. We have also found statistically significant association of a higher body mass index with worse clinical outcome - shorter duration of pain relief and less symptomatic improvement in both joints. We did not find significant prognostic factors (i.e., age, race, the number of comorbidities, use of opiates, and the location (hip versus shoulder) and severity of degenerative joint disease) for the clinical outcomes of injections. Discussion. Our results point towards a strong relationship between positive responses to intra-articular Hylan G-F 20 injections performed using fluoroscopic guidance in individuals with lower BMI who suffer from intractable shoulder and/or hip OA-related pain. Conclusion. Intraarticular Hylan G-F 20 injections for the symptomatic management of shoulder and hip osteoarthritis appear to be safe with better efficacy in lean individuals regardless of severity

Gene expression profile of the rat eye irido-corneal angle. NEIBank expressed sequence Tag analysis. Invest Ophthalmol Vis Sci.

PURPOSE. To characterize gene expression pattern in the combined tissues of the rat iridocorneal angle by expressed sequence tag (EST) analysis, as part of the NEIBank project. METHODS. RNA was extracted from dissected tissues of the rat iridocorneal angle (iris, ciliary body, trabecular meshwork, and Schlemm's canal) and used to construct unamplified, nonnormalized cDNA libraries in the pSPORT1 vector. Approximately 5000 clones were sequenced from the 5Ј-end. Clones were clustered and identified using the GRIST software, a procedure based on BLAST comparisons. Complete sequences of several novel cDNAs showing eye-preferred expression patterns were obtained. The expression patterns of several genes have been investigated by Northern blot and in situ hybridization, as well as by RT-PCR. RESULTS. After analysis and removal of non-mRNA sequences, 2195 independent clusters, potentially representing individual eye angle-expressed clones were obtained. The expression profile of the combined rat eye angle tissues was more similar to that of the human iris than to human trabecular meshwork. Several cDNAs encoding transcription factors essential for normal eye development and function including Pax-6, Six3, c-Maf, Maf1, Sox-4, Foxc1, Rx, and Ldb2 were present among sequenced clones. A number of tested cDNAs showed eyepreferred expression patterns. Myocilin, which is abundant in human eye angle tissues, was not observed in the rat collection; however, transcripts for three other olfactomedin-domain proteins were seen. Latrotoxin receptor (CL1AA) and optimedin were shown to be expressed in the iris and ciliary body, as well as in the ganglion and inner nuclear cell layers of the retina, whereas the rat orthologue of the human HNOEL-iso gene was expressed in the iris and sclera and less actively in the trabecular meshwork, retina, and optic nerve. CONCLUSIONS. The iridocorneal libraries are a good source of novel uncharacterized genes and molecular markers for the tissues of the eye angle. Although myocilin is not abundantly expressed in rat eye angle, other olfactomedin-containing genes are expressed there and may play important roles in normal eye function and disease. (Invest Ophthalmol Vis Sci