Lumbar spine intrathecal transplantation of neural precursor cells promotes oligodendrocyte proliferation in hot spots of chronic demyelination

Experimental autoimmune encephalomyelitis (EAE) is a basic and reliable model used to study clinical and pathological hallmarks of multiple sclerosis (MS) in rodents. Several studies suggest neural precursor cells (NPCs) as a significant research tool while reporting that transplanted NPCs are a promising therapeutic approach to treating neurological disorders, such as MS. The main objective was to approach a preclinical, in vivo scenario of oligodendrogenesis with NPCs, targeting the main chronic demyelinated lumbosacral milieu of EAE, via the least invasive delivery method which is lumbar puncture. We utilized MOG_35‐55 peptide to induce EAE in C57BL/6 mice and prior to the acute relapse, we intervened with either the traceable GFP⁺ cellular therapy or saline solution in the intrathecal space of their lumbar spine. A BrdU injection, which enabled us to monitor endogenous proliferation, marked the endpoint 50 days post‐induction (50 dpi). Neuropathology with high‐throughput, triple immunofluorescent, and transmission electron microscopy (TEM) data were extracted and analyzed. The experimental treatment attenuated the chronic phase of EAE (50 dpi; score <1) following an acute, clinical relapse. Myelination and axonal integrity were rescued in the NPC‐treated animals along with suppressed immune populations. The differentiation profile of the exogenous NPCs and endogenous BrdU⁺ cells was location‐dependent where GFP⁺‐rich areas drove undifferentiated phenotypes toward the oligodendrocyte lineage. In situ oligodendrocyte enrichment was demonstrated through increased (p < 0.001) gap junction channels of Cx32 and Cx47, reliable markers for proliferative oligodendroglia syncytium. TEM morphometric analysis ultimately manifested an increased g‐ratio in lumbosacral fibers of the recovered animals (p < 0.001). Herein, we suggest that a single, lumbar intrathecal administration of NPCs capacitated a viable cellular load and resulted in clinical and pathological amelioration, stimulating resident OPCs to overcome the remyelination failure in EAE demyelinating locale.     

Thyroid autoimmunity in the current iodine environment.

Iodine is essential for thyroid function. Thyroid disorders related to iodine deficiency decreased progressively with the continuous iodine prophylaxis and the increased iodine intake. An adverse effect resulting from iodine prophylaxis may be the induction of thyroid autoimmunity. Although experiments performed in animal models suggest that iodine could initiate or exacerbate thyroid autoimmunity, the role of iodine in humans remains controversial. Several observational studies in areas with adequate or high iodine intake suggest that there is an increase in the incidence of thyroid autoimmune disease. Moreover, intervention studies suggest that increased iodine intake may enhance thyroid autoimmunity too. However, not all studies generated the same findings, probably because of genetic, racial, and environmental differences. It seems that autoimmune exacerbation is a transient phenomenon. Studies have shown that in persons presenting thyroid antibodies, the levels of these antibodies progressively decrease when the majority of them react against a nonspecific pattern of thyroglobulin (Tg) epitopes. However, in a small number of these persons, the anti-Tg antibodies are similar to those in patients with patent thyroid autoimmune disease, reacting against specific immunodominant Tg epitopes, and their levels persist. One possible attractive explanation is that enhanced iodine intake increases the antigenicity of Tg through the incorporation of iodine into its molecule and the formation of iodinated Tg epitopes or even the generation of noniodinated pathogenetic Tg epitopes that are normally cryptic.     

Current trends of clinical and genetic characteristics influencing the resource use and the nurse-patient balance in an intensive care setting

PURPOSE: To determine the impact of resource use on the nurse/patient ratio in a pediatric intensive care unit (PICU). To examine the longitudinal influence of chronic or genetically influenced diseases on this interrelation. MATERIALS AND METHODS: Overall, 1586 patients admitted to the PICU through various modes of admission during a 5-year period were prospectively studied. RESULTS: The mean daily number of bed use increased from 5 to 8.1, leading to a significant skew from the ideal nurse/patient ratio of 1:1, to an overloaded one of 1:3-5. An increasing longitudinal trend of patients with metabolic diseases (P < .0001) or with genetic influence (62.8% in 1997, 70.7% in 2001) was noted. More patients with a genetic influence died than those without (13.8% vs 8.5%, P < .001), and more patients supported by mechanical ventilation suffered from a genetically influenced disease (64% vs 36%, P < .03). The mortality rate showed a trend for longitudinal reduction from 12.6% to 12%. CONCLUSIONS: The increasing trend of occupation of PICU bed and ventilator days by patients with chronic diseases may be related to the increasing trend of hospitalization of patients with recognized genetic influence. Although this new trend does not influence mortality, it significantly increases resource use and has a large impact on the staffing needs.     

Novel contributors to B cell activation during inflammatory CNS demyelination; An oNGOing process

Over the past two decades, the development of targeted immunotherapeutics for relapsing-remitting multiple sclerosis has been successfully orchestrated through the efficacious modulation of neuroinflammatory outcomes demonstrated in the experimental autoimmune encephalomyelitis (EAE) model. In this model, the focus of developing immunomodulatory therapeutics has been demonstrated through their effectiveness in modifying the pro-inflammatory Th1 and Th17-dependent neuropathological outcomes of demyelination, oligodendrocytopathy and axonal dystrophy. However, recent successful preclinical and clinical trials have advocated for the significance of B cell-dependent immunopathogenic responses and has led to the development of novel biologicals that target specific B cell phenotypes. In this context, a new molecule, B-cell activating factor (BAFF), has emerged as a positive regulator of B cell survival and differentiation functioning through various signaling pathways and potentiating the activity of various receptor complexes through pleiotropic means. One possible cognate receptor for BAFF includes the Nogo receptor (NgR) and its homologs, previously established as potent inhibitors of axonal regeneration during central nervous system (CNS) injury and disease. In this review we provide current evidence for BAFF-dependent signaling through the NgR multimeric complex, elucidating their association within the CNS compartment and underlying the importance of these potential pathogenic molecular regulators as possible therapeutic targets to limit relapse rates and potentially MS progression.