Regenerating Corticospinal Axons Innervate Phenotypically Appropriate Neurons within Neural Stem Cell Grafts.

Neural progenitor cell grafts form new relays across sites of spinal cord injury (SCI). Using a panel of neuronal markers, we demonstrate that spinal neural progenitor grafts to sites of rodent SCI adopt diverse spinal motor and sensory interneuronal fates, representing most neuronal subtypes of the intact spinal cord, and spontaneously segregate into domains of distinct cell clusters. Host corticospinal motor axons regenerating into neural progenitor grafts innervate appropriate pre-motor interneurons, based on trans-synaptic tracing with herpes simplex virus. A human spinal neural progenitor cell graft to a non-human primate also received topographically appropriate corticospinal axon regeneration. Thus, grafted spinal neural progenitor cells give rise to a variety of neuronal progeny that are typical of the normal spinal cord; remarkably, regenerating injured adult corticospinal motor axons spontaneously locate appropriate motor domains in the heterogeneous, developing graft environment, without a need for additional exogenous guidance

Comprehensive Monosynaptic Rabies Virus Mapping of Host Connectivity with Neural Progenitor Grafts after Spinal Cord Injury.

Neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. Mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. Using transgenic mouse spinal neural progenitor cell grafts expressing the TVA and G-protein components of the modified rabies virus system, we initiated monosynaptic tracing strictly from graft neurons placed in sites of cervical spinal cord injury. We find that graft neurons receive synaptic inputs from virtually every known host system that normally innervates the spinal cord, including numerous cortical, brainstem, spinal cord, and dorsal root ganglia inputs. Thus, implanted neural progenitor cells receive an extensive range of host neural inputs to the injury site, potentially enabling functional restoration across multiple systems

局所型前立腺癌に対する3次元原体照射後の晩期消化管障害に関連する臨床因子

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Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.

Neural progenitor cell (NPC) transplantation has high therapeutic potential in neurological disorders. Functional restoration may depend on the formation of reciprocal connections between host and graft. While it has been reported that axons extending out of neural grafts in the brain form contacts onto phenotypically appropriate host target regions, it is not known whether adult, injured host axons regenerating into NPC grafts also form appropriate connections. We report that spinal cord NPCs grafted into the injured adult rat spinal cord self-assemble organotypic, dorsal horn-like domains. These clusters are extensively innervated by regenerating adult host sensory axons and are avoided by corticospinal axons. Moreover, host axon regeneration into grafts increases significantly after enrichment with appropriate neuronal targets. Together, these findings demonstrate that injured adult axons retain the ability to recognize appropriate targets and avoid inappropriate targets within neural progenitor grafts, suggesting that restoration of complex circuitry after SCI may be achievable

Outcomes after stereotactic body radiotherapy for lung tumors, with emphasis on comparison of primary lung cancer and metastatic lung tumors

BACKGROUND: The goal of this study was to determine the prognostic factors associated with an improved overall outcome after stereotactic body radiotherapy (SBRT) for primary lung cancer and metastatic lung tumors. METHODS: A total of 229 lung tumors in 201 patients were included in the study. SBRT of 45 Gy in 3 fractions, 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions was typically used to treat 172 primary lungs cancer in 164 patients and 57 metastatic lung tumors in 37 patients between January 2001 and December 2011. Prognostic factors for local control (LC) and overall survival (OS) were analyzed using a Cox proportional hazards model. RESULTS: The median biologically effective dose was 105.6 Gy based on alpha/beta = 10 (BED10). The median follow-up period was 41.9 months. The 3-year LC and OS rates were 72.5% and 60.9%, and the 5-year LC and OS rates were 67.8% and 38.1%, respectively. Radiation pneumonitis of grades 2, 3 and 5 occurred in 22 petients, 6 patients and 1 patient, respectively. Multivariate analyses revealed that tumor origin (primary lung cancer or metastatic lung tumor, p < 0.001), tumor diameter (p = 0.005), BED10 (p = 0.029) and date of treatment (p = 0.011) were significant independent predictors for LC and that gender (p = 0.012), tumor origin (p = 0.001) and tumor diameter (p < 0.001) were significant independent predictors for OS. CONCLUSIONS: SBRT resulted in good LC and tolerable treatment-related toxicities. Tumor origin and tumor diameter are significant independent predictors for both overall survival and local control

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex

15-Deoxy-Δ12,14 Prostaglandin J2 Reduces the Formation of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

AIM: 15-deoxy-Δ¹²,¹⁴ prostaglandin J₂ (15d-PGJ₂) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ₂ can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ₂. METHODS: We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ₂ intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion. RESULTS: Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ₂, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ₂ treated mice. The 15d-PGJ₂ also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions. CONCLUSION: This is the first report 15d-PGJ₂, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ₂ may be a beneficial therapeutic agent for atherosclerosis