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Objective: GK-2 - hexamethylendiamide bis-(N-monosuccinil-L-glutamyl-L-lysine) - a novel low-molecular mimetic of nerve growth factor. In previous studies it was shown that GK-2 being administered 4 h after surgery completely prevents mortality in experimental model of intracerebral posttraumatic hematoma (IPH) in rats. The purpose of the study was to evaluate the «therapeutic window» of GK-2 in IPH model.
Method: IPH was simulated by the destruction of brain tissue in the area of internal capsule according to Makarenko AN et al. Animals were divided into 7 groups: sham-operated; animals with IPH treated by saline; and 5 groups of rats with IPH treated by GK-2 (1 mg/kg, intraperitoneally) with first administration 6, 9, 12, 18 or 24 hours after surgery, and then every 48 hours during 2 weeks.
Results: In sham-operated rats within the first day after surgery death-rate was 0%, and by day 14 increased up to 10%. In rats with IPH within the first day death-rate was 10%, and by day 14 increased up to 50%. In rats which received GK-2 within 6 hours after surgery survival rate increased, mortality by the 14th day was only 17%. Tendency to decrease in mortality was registered when GK-2 was injected first within 9 hours as well as within 12 hours after surgery (mortality was 30%). In rats with IPH treated by GK-2 with first administration 18 hours or 24 hours after surgery no protective effect of GK-2 was registered.
Conclusion: Thus, the results obtained show that GK-2 when administered firstly from 4 to 6 hours after surgery is able to increase survival in experimental animals in the model of intracerebral posttraumatic hematoma.