Science: New drug reduces brain infarction in stroke patients.

According to the World Health Organization, about 15 million people worldwide suffer strokes each year, 5 million of them die and another 5 million suffer from permanent severe disabilities.
the current clinical treatment for ischemic stroke is limited to rapid thrombosis or removal of intravascular thrombosis to restore brain perfusion, there is an urgent need to develop new neuroprotective methods to treat stroke as a supplementary means of rapid brain reperfusion.
July 1, 2020 , researchers at the University of Pittsburgh in the United States published a new study published in Science Advances, which found a new injectable neuroprotective treatment peptide with hemo-brain barrier permeability, TAT-DP-2, that reduces infarction area and protects long-term nerve function after stroke.
DOI: 10.1126/sciadv.aaz8110 voltage gated potassium channel Kv2.1 is a known key channel for regulating neuron apoptosis, which causes the loss of cytoplasmic potassium in neurons after insertion into the dendritic cell cluster membrane, resulting in apoptosis, and the overly expression of the end of the cogen channel Kv2.2 (CT) can destroy Kv2.1 surface cluster, which inhibits the apoptonicarium.
in this study, the researchers identified and validated the key sequence of Kv2.2 CT-mediated Kv2.1 declustering and neuroprotective action, and found that the resulting DP-2 (TAT-DP-2) compound with a cell-permeable transcription reactivation factor (TAT) connection can induce significant dispersion of Kv2.1 surface clusters for up to 24 hours.
because vesicle-related membrane protein A (VAPA) can collect Kv2.1 into clusters, the researchers tested the ability of DP-2 to bind to VAPA and found that the two could not be combined.
assessing whether TAT-DP-2 can disrupt Kv2.1-VAPA interactions in vitro, the researchers found that the peptide, while not directly binding to VAPA, can effectively disrupt Kv2.1-VAPA binding alone.
TAT-DP-2 replaces Kv2.1-VAPA in cortical neurons The researchers used dual electrode voltage clamps to monitor in real time the changes in the time of Kv2.1-mediated potassium currentbefore before and after TAT-DP-2 processing, and found that The TAT-DP-2-induced Kv2.1 declustering could effectively inhibit the increase of potassium-promoting potassium in neurons by destroying membrane insertion in neurons.
at the same time, in vitro testing found that TAT-DP-2 has a protective effect on the nerves in the cortex neurons.
then, the researchers injected the mice with TAT-DP-2 in the peritoneal membrane, and the results showed that the drug was effectively delivered to the cerebrovascular and brain essence, and that it was able to effectively mediate the rapid dispersion of Kv2.1 surface clusters in the body.
, the researchers used a mouse model of ischemic stroke and one-sided cerebral octic aumcis (MCAo) that produced a highly replicable infarction, for MCAo therapy and re-injection, and tAT-DP-2 toad 1 and 6 hours after the reperfusion began, and found that TAT-DP-2 has a powerful neuroprotective effect in mice, not only to reduce the size of cerebral infarction. "In clinical practice, there is no drug that can prevent cell death after a stroke, and these trials provide some early evidence for drug targeting, and we hope to one day apply these results to the treatment of clinical patients," said Anthony Schulien, lead author of the report on tat-DP-2 injections in the abdominal cavity of
mice.
" References: s1. Targeted of the Disruption Kv2.1-VAPA Association provides s neuroreagain sischemstroke in mice by declustering Kv2.1 channels.