ic inhibition of AhR leads to a powerful reduction of infarct volume in mice subjected to MCAO. AhR antagonist TMF enhanced CREB transcriptional activity, normalizing BDNF levels and decreasing apoptosis by affecting apoptosis-related genes (lowered proapoptotic proteins p53 and Puma and increased the anti-apoptotic Bcl-X) just after MCAO [269]. Similarly, TMF decreased infarct volume, inhibited astrogliosis, microgliosis and apoptosis in rodent HSV-2 Inhibitor Purity & Documentation brains undergoing MCAO [231,270]. Additionally, TMF treatment modulated gene and protein expression related to neurogenesis just after stroke, major an improved proliferation of neural progenitor cells in the ipsilesional neurogenic zones [231]. Tanaka and colleagues [252] showed that AhR antagonist CH223191 inhibited MCAO-increased the expression of Tnfa and edema progression, and improved the neurological severity scores in mice. The administration of 3,3′-diidnolylmethane (DIM), a selective AhR modulator, protected hippocampal neurons against hypoxia/ischemia through inhibition of AhR signaling pathway. The neuroprotective action of AhR antagonism against ischemia likely requires an inhibition of apoptosis and autophagy [271,272]. Moreover, an in vivo study confirmed that DIM protected rat pups against perinatal asphyxia through inhibition of AhR and NMDA signaling pathways [273]. The newest data showed that intracerebral hemorrhage in mouse induced the expression of AhR in microglia and neutrophils. DIM attenuated activation of microglia/macrophages and astrocytes and diminished infiltration of neutrophils in to the hematoma. DIM also decreased AhR-regulated Il6 and Cxcl1 [274]. These benefits strongly recommend an involvement of AhR in immune cell functions during intracerebral hemorrhage. Although promising experimental evidence on the crucial function of AhR signaling pathway in HSP70 Activator web stroke pathology was obtained, this topic continues to be unexplored and calls for additional study. 5. Conclusions The progress in mechanical therapies (i.e., stenting or mechanical thrombectomy) along with the use of thrombolytic drugs in stroke or in myocardial infarction reduced substantially the rate of mortality. Even so, scientists still have to appear for new extra effective and safer drugs which will be able to prolong a short time-window of currently accessible therapies. Future therapies really should concentrate not merely on well-known ischemia-induced mechanisms, but also on new molecular targets (i.e., nuclear receptors) and compounds (i.e., SERMs, SAhRMs), which can assist in reduction of infarct-induced damage and significantly improve patient’s life.Author Contributions: J.R. Conceptualization, Writing–Original Draft Preparation, Writing–Review Editing, Supervision, L.C. Writing–Review Editing, P.G. Conceptualization, Writing–Original Draft Preparation, Visualization, M.M. Writing–Review Editing, B.M. Writing–Review Editing, L.S. Writing–Original Draft Preparation, Supervision. All authors have read and agreed towards the published version of the manuscript. Funding: This analysis received no external funding. Institutional Evaluation Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Not applicable. Conflicts of Interest: The authors declare no conflict of interest.Int. J. Mol. Sci. 2021, 22,19 ofAbbreviationsAHR AIP Akt (PKB) ANP AP-1 ARNT BBB CK-MB CNS CREB CVDs CXCL1 CYP1A1 DIM DPN E2 ER ERE ERK ER ER GPER GSK-3 HIE HSP90 I/R IL-6 JNK KO LAD LPS LV MAPK MI miRNA MMP mPTP MSCs MT MTA1 mTOR N