TAT-CIRP, a trans-activating (Tat) cold-inducible RNA-binding protein-derived peptide, functions as an inhibitor of myeloid differentiation protein 2 (MD2). It has demonstrated significant neuroprotective effects against ischemic and hemorrhagic stroke in mouse models [1].

TAT-CIRP at a concentration of 5 μM attenuates NMDA-induced (50 μM; 1 hour) apoptosis and necrosis in neuronal cells through a TLR4-independent pathway [1].

TAT-CIRP, at dosages of 5-20mg/kg, mitigates cerebral damage following an ischemic stroke induced by middle cerebral artery occlusion (MCAO) in mice. Tat, which is the transduction domain of the human immunodeficiency virus-type 1, is employed as a control peptide [1]. Administered intravenously to mice at a single dose of 20 mg/kg, TAT-CIRP crosses the blood-brain barrier, attaining a peak concentration (C max) of 4762.6 μg/L and a half-life of approximately 90 minutes [1]. Moreover, repeated daily intravenous administrations of TAT-CIRP at 20 mg/kg and 100 mg/kg for 7 days exhibited minimal toxicity and proved to be safe in mice [1]. Additionally, TAT-CIRP reduced cerebral ischemic damage in rhesus monkeys [1].