scholarly journals The central nervous system is a target of acute graft versus host disease in mice

Blood ◽  
2013 ◽  
Vol 121 (10) ◽  
pp. 1906-1910 ◽  
Author(s):  
Steffen Hartrampf ◽  
Jarrod A. Dudakov ◽  
Linda K. Johnson ◽  
Odette M. Smith ◽  
Jennifer Tsai ◽  
...  

Key Points The central nervous system can be a direct target of alloreactive T cells during GVHD. Central nervous system damage in mouse models of GVHD lead to deficits in learning and increased anxiety behavior.

2018 ◽  
Vol 2 (1) ◽  
pp. 10-13 ◽  
Author(s):  
Jordan Gauthier ◽  
Patrick Vermersch ◽  
Paul Chauvet ◽  
Pauline Varlet ◽  
Valérie Coiteux ◽  
...  

Key Points Fingolimod could be efficient to treat GVHD of the central nervous system. Further research should explore the use of fingolimod and other sphingosine-1-phosphate receptor agonists to prevent or treat GVHD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Janaki Manoja Vinnakota ◽  
Robert Zeiser

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for patients with hematological malignancies. Acute Graft versus host diseases (GVHD) is a major immune mediated side effect of allo-HCT that can affect the central nervous system (CNS) in addition to post-allo-HCT vascular events, drug toxicity or infections. Here we summarize and discuss recent preclinical data on the CNS as a target of acute GVHD and the known mechanisms contributing to neurotoxicity with a focus on microglia and T cells. We also discuss open questions in the field and place the findings made in mouse models in a clinical context. While in mice the neurological deficits can be assessed in a controlled fashion, in patients the etiology of the CNS damage is difficult to attribute to acute GVHD versus infections, vascular events, and drug-induced toxicity. Ultimately, we discuss novel therapies for GVHD of the CNS. Our understanding of the biological mechanisms that lead to neurotoxicity after allo-HCT increased over the last decade. This review provides insights into CNS manifestations of GVHD versus other etiologies of CNS damage in mice and patients.


2016 ◽  
Author(s):  
◽  
Christopher M. Owens

Injuries to nerves vary in their consequences, from weakened sensation and motor function to partial or complete paralysis. In the latter case, affecting about twenty thousand Americans yearly, the injury is debilitating and results in a significant decrease in quality of life. Currently there is no effective treatment for damage to the central nervous system, in particular the spinal cord. Compared to the injuries to the central nervous system, damage in the peripheral nerves, is more common, with about sixty thousand occurrences annually. The cost of associated surgical procedures and due to loss of function is in the billions. In this thesis we present work towards the construction and testing of a fully cellular, patented nerve graft, one amongst the first of its kind. For the fabrication of the graft we are the first to employ bioprinting (either implemented through a special purpose 3D bioprinter or manually), a novel tissue engineering method rapidly gaining acceptance and utility. We first review the status of bioprinting. We then detail the fabrication process. Next we report on the testing of the graft in an in vivo animal model through electrophysiology and histology. This is followed by the introduction of a novel in vitro model, aimed at providing a fast, inexpensive and reliable method to test engineered nerve grafts. We describe our work on the optimization of the in vitro assay and then the testing of the graft using the optimized assay. We conclude with a summary of our accomplishments and make suggestions for some exciting future applications of our approach.


2009 ◽  
Vol 84 (11) ◽  
pp. 764-766 ◽  
Author(s):  
Hisashi Yamamoto ◽  
Naoyuki Uchida ◽  
Kazuya Ishiwata ◽  
Hideki Araoka ◽  
Shinsuke Takagi ◽  
...  

1982 ◽  
Vol 60 (7) ◽  
pp. 1037-1045 ◽  
Author(s):  
William J. Racz ◽  
Laurie J. S. Vandewater

Methylmercury is a widespread and highly toxic environmental pollutant. The source of the substance in the environment is industrial and agricultural use. Chronic methylmercury poisoning is characterized by peripheral and central nervous system damage. The rate of absorption and distribution of this organomercurial into neural tissue determines the rate of development and the severity of the neural lesion. Furthermore, the rate of metabolism and excretion of an organomercurial will greatly influence its neural toxicity. There are differences in the accumulation of methylmercury in different regions of the brain, as well as by the different cell types in these regions. The significance of this variable accumulation of methylmercury is not known. Methylmercury influences a large number of neurocellular functions ranging from inhibition of membrane integrity to alteration in the synthesis and release of transmitter substances.


Blood ◽  
2017 ◽  
Vol 129 (3) ◽  
pp. 324-332 ◽  
Author(s):  
Amrita Desai ◽  
Madhura G. Joag ◽  
Lazaros Lekakis ◽  
Jennifer R. Chapman ◽  
Francisco Vega ◽  
...  

Key Points POAML (specifically Ann Arbor stage I disease) has an excellent clinical outcome, with only a few patients succumbing to lymphoma. POAML patients face a continuous risk of distant relapse, including in the central nervous system, and transformation to aggressive lymphoma.


1988 ◽  
Vol 89 (4) ◽  
pp. 543-546 ◽  
Author(s):  
Emilie Rouah ◽  
Regina Gruber ◽  
William Shearer ◽  
Dawna Armstrong ◽  
Edith P. Hawkins

Author(s):  
Daiva Bartkevičienė ◽  
Ingrida Pilypienė ◽  
Danielius Serapinas ◽  
Brigita Vaigauskaitė ◽  
Rasa Aurelija Vankevičiūtė ◽  
...  

Abstract Objective The aim was to identify the critical levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A in umbilical cord blood that could be used as markers for predicting the central nervous system (CNS) damage and retinopathy of prematurity (ROP) in preterm infants. Study Design A total of 158 preterm infants, born at 22 to 34 weeks of gestation, were evaluated in the first week after birth and at 36 to 37 weeks of postconceptual age. Results A significant relationship between CNS changes and concentrations of IL-6 (p < 0.001) and TNF-α (p < 0.001) in umbilical cord blood at 22 to 34 weeks of gestation was determined. The concentration of IL-6 >13.0 pg/mL predicts significant CNS damages in 36 to 37-week infants (p = 0.013). ROP was diagnosed in 24.8% infants (n = 149). It was detected that the levels of TNF-α >116.4 pg/mL (p < 0.001) and IL-6 >13.0 pg/mL (p < 0.05) in umbilical cord blood could predict 2 to 3/3 to 4 stages of ROP. Conclusion Critical values of IL-6 and TNF-α in predicting ≥grade III intraventricular hemorrhage in the early adaptation and in predicting marked CNS damages and severe ROP stages in the later adaptation of preterm infants were determined.


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