The role of NLRP2 inflammasome in neuro-parainflammation induced by cortical spreading depolarization

Migraine is a common headache syndrome in the general population. Inflammation resulting from activation of the trigeminovascular system plays an important role in its pathophysiology. Cortical spreading depolarization (CSD) is accepted as the electrophysiological correlate of migraine aura. It is thought that the triggering of CSD leads to an increase in neuronal activity, opening of neuronal pannexin channels and a proinflammatory response in astrocytes via NF-ҝβ. It has been shown in the literature that NLRP2, a member of the inflammasome family, is expressed in astrocytes and contributes to neuroinflammation by forming an inflammasome complex. Experimental studies have shown that ATP-induced pannexin and purinergic receptor activation results in the formation of an inflammasome complex. The aim of this study was to investigate the role of NLRP2 inflammasome complex in neuroinflammation induced by noninvasive induction of CSD in optogenetically inducible transgenic Thy1-ChR2-YFP mice. Brain tissue was obtained at 5 different time points (15th minute, 5th, 24th, 48th and 72nd hours) following CSD and NLRP2 labeling properties in the sections were examined by immunofluorescence labeling and it was shown in which cells NLRP2 was expressed. While NLRP2 expression was prominent in NeuN (+) neuronal cells in the cortical and subcortical areas in the control and naive groups, a significant decrease in immunoreactivity was detected at 15 minutes, 5 and 24 hours after CSD, and similar levels were observed at 48 and 72 hours. It was shown that NLRP2 co-localized significantly less with the astrocyte marker S100β. At the same time points, CSD was induced in C57/BL6 mice and cortices were taken for protein analysis by Western blotting (WB). Similar to the results of immunofluorescence imaging, NLRP2 protein levels were found to be decreased in early CSD brains compared to naive brains, although protein levels were not significant in WB. To the best of our knowledge, this is the first study in the literature to examine the temporal changes of NLRP2 inflammasome in parenchymal neuroinflammation after CSD, which is accepted as a correlate of migraine aura. The result of this study, which is contrary to the increase in NLRP3 inflammasome in neurons after CSD, can be interpreted as a result that NLRP2 may be a negative regulator of NLRP3. With further research, it may be possible to determine the role of NLRP2 in neuroinflammation by pharmacologic or genetic manipulation.