Background:
A dimeric dipeptide mimetic of the BDNF loop 4, bis(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106), which activates TrkB, PI3K/AKT, MAPK/ERK and PLC-γ1 was created at the V.V. Zakusov Research Institute of Pharmacology. GSB-106 showed neuroprotective activity in vitro and in vivo at systemic administration.
Objective:
In this work, we studied the GSB-106 effect on the cerebral infarct volume, as well as on neurogenesis and synaptogenesis under experimental ischemic stroke, induced by intravascular occlusion of the middle cerebral artery in rats.
Methods:
GSB-106 was administered i.p. in a dose of 0.1 mg/kg 24 h after surgery and then once a day, with the end of administration on the day 6 after surgery. On the day 7 brain samples were collected for morphometric and biochemical (Western-blot) analysis.
Results:
It was established that GSB-106 reduced the brain damage volume by 24%, restores impaired neurogenesis and/or gliogenesis (by Ki-67) in the hippocampus and in the striatum and completely restored the reduced immunoreactivity to synaptic markers synaptophysin and PSD-95 in the striatum.
Conclusions:
Thus, the dimer dipeptide BDNF mimetic GSB-106 exhibits neuroregenerative properties at clinically relevant time window (24 h) in a model of ischemic stroke presumably due to stimulation of neurogenesis (and/or gliogenesis) and synaptogenesis.