Detection of IL A early in blood samples from

Detection of IL-17A early in blood samples from gestational week 5–16 was also investigated by Salazar et al. [25], who reported that patients who later developed preeclampsia had a significantly higher percentage of CD4 + IL-17 + out of total CD4 + T cells, as compared to patients who did not develop preeclampsia. Together these results suggest that a subgroup of pregnant women displayed a proinflammatory state with an increased concentration of Th17 BEC and increased Plasma IL-17A already in the first trimester, and that this is associated with the risk of developing pregnancy-induced hypertensive disorders.
Competing interests
Funding The study was supported by a grant from the Independent Research Fund Denmark, and Bagermester August Jensen og Hustrus legat.
Introduction Spinal cord injury (SCI) is a devastating condition affecting about 2.5 million people worldwide which compromises major motor, sensory, autonomic and reflex functions and profoundly impacts on the quality of life, life expectancy and health expenses [1]. The neurologic damage caused by SCI is the result of two distinct events, a primary and a secondary injury, which involve different mechanisms [2], [3]. Primary injury refers strictly to the cell death directly resultant from traumatic mechanical damage, which usually affects spinal grey matter to a greater extent than white matter. Secondary injury starts with the onset of inflammation and is characterized by increased blood-brain barrier permeability, glial and neuronal cell apoptosis, alongside a complex neuroinflammatory response that may last for months and years after the initial trauma [2], [4]. Patients with SCI often develop chronic neuropathic pain, which further deteriorates their quality of life [5]. This condition results from functional and structural plastic changes that occur centrally following injury to spinal cord neurons and glia, and include changes in receptor function and signaling mechanisms leading to increased neuronal excitability in somatosensory pathways [6]. Currently, the treatment options available for neuropathic pain following SCI are limited, only modestly effective and have serious side effects that frequently limit their usefulness [7], [8], [9]. Thus, considerable efforts have been directed at identifying novel targets of drug action which could lead to improved treatment of SCI-induced neuropathic pain. Endothelins (ETs) are peptides expressed in both the peripheral and the central nervous systems, which can contribute to sensory changes seen in animal models of inflammatory, cancer and neuropathic pain [10], [11]. All three mammalian isoforms (ET-1, ET-2 and ET-3) activate specific G protein-coupled endothelin type A (ETAR) and/or endothelin type B (ETBR) receptors. The ETAR shows higher affinity for ET-1 and ET-2 than ET-3 and is selectively blocked by several antagonists including BQ-123. The ETBR binds all three ET isoforms indiscriminately and is blocked by BQ-788 [12], [13]. Receptor binding studies in mammals, including humans demonstrated that endothelin receptors are distributed throughout the normal spinal cord [14], [15], [16].