This research investigates two novel therapeutic strategies for ischemic stroke: osteopontin (OPN)–based neuroprotection and thyronamine-induced hypothermia. OPN was shown to protect primary cortical neurons from ischemic injury in vitro and to significantly reduce infarct size in a murine stroke model, through mechanisms dependent on its RGD motif and activation of Akt and MAPK signaling. Thrombin-cleaved OPN, intranasal delivery, and peptide-based OPN mimetics further enhanced neuroprotective efficacy. In parallel, the thyroxine derivatives 3-iodothyronamine (T1AM) and thyronamine (T0AM) induced mild hypothermia and significantly reduced ischemic brain injury when administered before or after stroke. Together, these findings identify OPN-derived therapeutics and thyronamine-induced hypothermia as promising approaches for stroke treatment.
