Adenosine and Neopterin Levels in Cerebrospinal Fluid of Patients with Neurological Disorders.

Abstract

Wedetermined the cerebrospinal fluid (CSF) levels of adenosine, a mediator of cerebral blood flow regulation, and neopterin, a macrophage-producing compound, in patients with neurological disorders. Compared to control subjects, the adenosine levels were significantly increased in the patients with acute-stage cerebral infarction (n=12, p<0.0001), acute meningitis (n=10, p<0.0001), or amyotrophic lateral sclerosis (ALS, n=12, p<0.05) (Mann-Whitney U-test). The neopterin levels were significantly increased in the 41 patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP,p<0.0001), acute meningitis (p<0.0001), ALS (p<0.05) (Mann-Whitney U-test), or acute-stage cerebral infarction (p<0.005, Student's t-test). In the analysis of 41 HAM/TSPpatients, the neopterin levels were significantly correlated with the cell number and glucose levels in the CSF, and were a sensitive marker of inflammation. Several of the HAM/TSP patients with increased adenosine levels were probably complicated with other diseases. The increased neopterin levels in the HAM/TSPgroup persisted, suggesting that the mononuclear cellular infiltration remained for a long time. (Internal Medicine 38: 133-139, 1989)

Central Nervous System Activation of the Indoleamine‐2,3‐Dioxygenase Pathway in Human T Cell Lymphotropic Virus Type I–Associated Myelopathy/Tropical Spastic Paraparesis

“…Short duration of disease (!4.5 years) is characterized pathologically by "active chronic" CNS lesions, featuring marked inflammatory changes; an equitable distribution of CD4 ϩ and CD8 ϩ cells and macrophages; increased expression of IL-1b, TNF-a, and IFN-g; and frequent distribution of cytotoxic T cells and NK cells, immune system cells that target intracellular pathogens [3]. The significantly increased neopterin level among these patients is consistent with results obtained from Japanese HAM/TSP patients and indicates immune activation in the CNS [12].…”

Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis

“…In pathological conditions, extracellular adenosine levels are often significantly elevated (Yoshida et al, 1999), as neurons lose their structural integrity during degeneration and glia become reactive in response to neuronal degeneration. We have observed increased release of ATP from cultured SOD1G93A + astrocytes (Kawamata et al, 2014).…”

“…Adenosine levels are also significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS patients (Yoshida et al, 1999). Here we investigated the role of A 2a R-mediated adenosine signaling in motor neuron cell death and ALS-related motor phenotypes using both in vitro and in vivo models with complementary genetic and pharmacological approaches.…”

CSF markers in amyotrophic lateral sclerosis

“…Anti-neural antibodies against GM1-gangliosides, asialo-GM1-gangliosides and sulfatides : Immune response; activation of microglia (Moreau et al 2005;Ganesalingam et al 2011;Goldknopf et al 2006;Sekizawa et al 1998;Tsuboi and Yamada 1994;Yoshida et al 1999;Tanaka et al 2006;Glabinski et al 1997;Graves et al 2004;Wilms et al 2003;Almer et al 2002;Mitchell et al 2009;McGeer and McGeer 2002;Niebroj-Dobosz et al 1999) Glial activation markers Erythropoietin (EPO) ; A neurotrophic factor (Brettschneider et al 2006d) S100b…”

“…In the CSF, increased concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), complement factors C3 and C4, peroxynitrite, prostaglandin E2, neopterin, monocyte chemoattractant protein-1 (MCP-1), granulocyte colony stimulating factor (G-CSF) and antibodies against various cellular structures have been reported (Almer et al 2002;Ganesalingam et al 2011;Goldknopf et al 2006;Graves et al 2004;McGeer and McGeer 2002;Mitchell et al 2009;Moreau et al 2005;Sekizawa et al 1998;Tanaka et al 2006;Tsuboi and Yamada 1994;Yoshida et al 1999;Glabinski et al 1997;Wilms et al 2003).…”