Synthetic peptides are an important breakthrough in the treatment of stroke

Surveys show that one out of every six people in the world will have a stroke, one person will die from a stroke every six seconds or so, and one person will be disabled for life because of a stroke every six seconds. Stroke is a group of diseases with cerebral ischemia and hemorrhagic damage as the primary clinical manifestations, also known as stroke or cerebrovascular accident, which can cause limb paralysis, language disorder, dysphagia, cognitive dysfunction and mental depression, etc. It has a very high mortality, disability rate and high recurrence rate.

Stroke causes great harm to people’s life and health. “Thrombolytic therapy within 4.5 hours is now a strongly recommended treatment option for stroke, but only after the use of neuroimaging to distinguish ischemic from hemorrhagic strokes.” Therefore, it is of interest to find a common therapeutic target for the treatment of ischemic and hemorrhagic stroke.

Investigators developed a peptide that interferes with myeloid differentiation protein 2 in vitro and protects neurons from excitotoxic damage.

Synthetic peptides are an important breakthrough in the treatment of stroke

TAT-CIRP(TC) protected the brain of mice and reduced brain tissue loss 28 days after hemorrhagic stroke compared with saline. MD2(myeloid differentiation protein 2) causes programmed cell necrosis in neurons in two autonomous ways.

The peptide is a trans-excited cold-inducible RNA-binding protein (Tat-CIRP). The researchers interpreted the neuroprotective effects of ischemic and hemorrhagic strokes in mice in two different ways – by injecting mice with Tat-CIRP and by deleting the MD2 gene. In the larger rhesus monkey model, injection of Tat-CIRP reduced the volume of dead brain tissue and maintained neurological function at 30 days after ischemic stroke.

If no toxicity was detected when using high dose of Tat-CIRP in mice, it indicated that Tat-CIRP could penetrate the blood-brain barrier and exhibit relatively high stroke therapeutic coefficient. Even when administered 6 hours after stroke, Tat-CIRP safely prevented neuronal loss and reduced brain tissue loss in mouse and nonhuman primate models of ischemic and hemorrhagic stroke.

In addition, MD2 was shown to cause neuronal apoptosis and necroptosis via a TLR4-independent Sam68-related cascade. Collectively, Tat-CIRP conferred potent neuroprotective efficacy in rodent and gyriencephalic non-human primate stroke. Efforts should be deepened to translate these findings into care for patients with ischemic and hemorrhagic stroke.