Expression of Interleukin‐17 in Ischemic Brain Tissue

Abstract

Ischemic brain injury is acute local inflammation, leading to accumulation of pro-inflammatory cytokines. Cytokines influence the recruitment of leucocytes and play a key role in the inflammatory injury processes. Recently, a number of studies have demonstrated a close relationship between brain ischemia and cytokines. Interleukin-17 (IL-17) is a newly identified T-cell-specific cytokine. In this study, we evaluated the source and the action of IL-17 over the course of cerebral ischemia in rats (Sprague-Dawley) and humans. The levels of IL-17 in the ischemic hemisphere of the human brain, which was removed at necropsy, were assayed immunohistochemically. In rats, permanent middle cerebral artery occlusion (pMCAO) was obtained by inserting nylon monofilament into the right external carotid artery, occluding the right middle cerebral artery. The expression of IL-17 mRNA in rat was assayed using oligoprobe in situ hybridization. IL-17 production by neuroglial cells was assayed by double-staining using antibody glial fibrillary acidic protein (GFAP) and antibody IL-17. Levels of IL-17 were elevated in the ischemic hemispheres of human brain compared with the opposite normal hemispheres and peaked at days 3-5 after brain ischemia. The IL-17-positive cells were found in the ischemic lesion region. IL-17 mRNA was also elevated in ischemic hemispheres of pMCAO-operated rats, which were slightly elevated after 1 h and peaked at 6 days. IL-17 and GFAP double-stained were extensive in rat ischemic hemisphere. The ischemia-induced IL-17 expression in human brain reported here for the first time was very similar to that in rat model except that the peak was slightly earlier. We found for the first time that IL-17 was involved in an intense inflammatory reaction of brain ischemic injury in human. In pMCAO-operated rats, our findings suggest that IL-17 is produced by the neuroglial cells in the brain region undergoing ischemic insult. We suggest that in additional to T cells the neuroglial cell may be another cellular origin of IL-17 in later progression of brain ischemia.

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

“…Peripheral neutralization of IL-17A has been shown to provide protection against ischemic damage (Gelderblom et al, 2012), and elevated levels of IL-17 expressing blood mononuclear cells have been observed in human stroke patients (Kostulas et al, 1999). cd T cells have been shown to infiltrate into the ischemic brain parenchyma at later stages of the injury, and the levels of brain IL-17A after ischemia are increased at 3 days poststroke (Li et al, 2005;Shichita et al, 2009). Even though the presence of brain cd T cells nor the levels of brain IL-17A were not analyzed in this study, it may be that the levels of plasma IL-17A at the early 24 h time point in the current study reflect on increased activation of cd T cells in the periphery.…”

Neutrophil to Lymphocyte Ratio Predicts Short-Term Functional Outcome in Acute Ischemic Stroke

“…Lymphocytes are elevated 3-6 days after stroke in the ischemic brain [38]. Tcell lymphocytes may play an important role in repairing inflamed tissues [39,40].…”

Experimental Model of Cerebral Hypoperfusion Produced Memory-learning Deficits, and Modifications in Gene Expression

“…Las células inflamatorias y las citoquinas desempeñan un papel clave en los procesos de daño neuronal (Li et al, 2005). Crecientes evidencias indican que las citoquinas están involucradas en el inicio y desarrollo de la isquemia cerebral (Li et al, 2001;Offner et al, 2009;Wang et al, 2009).…”

“…Sin embargo, poco se conoce acerca de los cambios en la expresión de il-17 en el curso de la isquemia cerebral, especialmente en humanos (Li et al, 2005). Algunos estudios indican que IL-17 aumenta en los hemisferios isquémicos, después de la oclusión permanente de la arteria cerebral media en ratas (Li et al, 2001;Guozhong et al, 2002;Li et al, 2005).…”

“…2) se incrementó en los animales con OPACC. La mayor parte de los trabajos que estudian la expresión de la IL-17 en el tejido cerebral isquémico plantean que, los niveles de ARN mensajero de IL-17 pueden ser detectados desde una hora hasta seis días post-lesión (Li et al, 2001;Li et al, 2005;Wang et al, 2009). Según lo propuesto en la literatura, IL-17 juega un papel importante en la etapa tardía del daño cerebral, y se ha sugerido que tiene un patrón de expresión tardío en la isquemia cerebral (Li et al, 2001).…”