Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration in the brain and spinal cord. Progressive paralysis of the diaphragm and other respiratory muscles leading to respiratory dysfunction and failure is the most common cause of death in ALS patients. Respiratory impairment has also been shown in animal models of ALS. Vascular pathology is another recently recognized hallmark of ALS pathogenesis. Central nervous system (CNS) capillary damage is a shared disease element in ALS rodent models and ALS patients. Microvascular impairment outside of the CNS, such as in the lungs, may occur in ALS, triggering lung damage and affecting breathing function. Stem cell therapy is a promising treatment for ALS. However, this therapeutic strategy has primarily targeted rescue of degenerated motor neurons. We showed functional benefits from intravenous delivery of human bone marrow (hBM) stem cells on restoration of capillary integrity in the CNS of an superoxide dismutase 1 (SOD1) mouse model of ALS. Due to the widespread distribution of transplanted cells via this route, administered cells may enter the lungs and effectively restore microvasculature in this respiratory organ. Here, we provided preliminary evidence of the potential role of microvasculature dysfunction in prompting lung damage and treatment approaches for repair of respiratory function in ALS. Our initial studies showed proof-of-principle that microvascular damage in ALS mice results in lung petechiae at the late stage of disease and that systemic transplantation of mainly hBM-derived endothelial progenitor cells shows potential to promote lung restoration via re-established vascular integrity. Our new understanding of previously underexplored lung competence in this disease may facilitate therapy targeting restoration of respiratory function in ALS.
Convincing evidence of blood-spinal cord barrier (BSCB) alterations has been demonstrated in amyotrophic lateral sclerosis (ALS) and barrier repair is imperative to prevent motor neuron dysfunction.We showed benefits of human bone marrow-derived CD34+ cells (hBM34+) and endothelial progenitor cells (hBM-EPCs) intravenous transplantation into symptomatic G93A SOD1 mutant mice on barrier reparative processes. These gains likely occurred by replacement of damaged endothelial cells, prolonging motor neuron survival. However, additional investigations are needed to confirm the effects of administered cells on integrity of the microvascular endothelium. The aim of this study was to determine tight junction protein levels, capillary pericyte coverage, microvascular basement membrane, and endothelial F-actin status in spinal cord capillaries of G93A SOD1 mutant mice treated with human bone marrow-derived stem cells. Tight junction proteins were detected in the spinal cords of cell-treated vs. nontreated mice via western blotting at four weeks post-transplant. Capillary pericyte, basement membrane laminin, and endothelial F-actin magnitudes were determined in cervical/lumbar spinal cord tissues in ALS mice, including controls, by immunohistochemistry and fluorescent staining. Results showed that celltreated vs. media-treated ALS mice substantially increased tight junction protein levels, capillary pericyte coverage, basement membrane laminin immunoexpressions, and endothelial cytoskeletal F-actin fluorescent expressions. The greatest benefits were detected in mice receiving hBM-EPCs vs. hBM34 + cells. These study results support treatment with a specific cell type derived from human bone marrow towards BSCB repair in ALS. Thus, hBM-EPCs may be advanced for clinical applications as a cellspecific approach for ALS therapy through restored barrier integrity.
Little is known about the community of dragonflies and damselflies in Tampa Bay, Florida, USA. To address this gap, we conducted 2 longitudinal surveys of adult odonates in a natural floodplain of the Hillsborough River in 2013 and 2017. Along with abundance and species diversity, we also measured intraspecific variation in body size, sexual dimorphism, wing-cell asymmetry, and water mite ectoparasitism. Our first weekly survey from Oct 2013 to Oct 2014 sampled 327 adults (230 female, 97 male) from 8 dragonfly species, with the eastern pondhawk (Erythemis simplicicollis Say; Odonata: Libellulidae) representing 79% of captures, followed by the second most abundant (14%), the Florida non-native and neotropical hyacinth glider (Miathyria marcella Selys; Odonata: Libellulidae). Our second weekly survey from Sept to Dec 2017, which focused on both damselflies and dragonflies and captured 205 adults from 8 species, with the fragile forktail (Ischnura posita Hagen; Odonata: Coenagrionidae) being the most abundant with 70% of captures. Female-biased sexual size dimorphism was found in both E. simplicicollis and I. posita; however, both sexes were equally variable in size and symmetric in a meristic trait. Female and male M. marcella were equally variable, monomorphic, and symmetric. Combing symmetry data from each sex, only I. posita damselflies were asymmetric overall. Finally, we did not observe any parasitism by larval water mites in either survey. We aim to continue surveys to track seasonal and climate-driven changes in dragonfly diversity and phenology in this region.
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