3- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, firstname.lastname@example.org
Traumatic brain injury (TBI) is a cerebral pathology that has severe medical, social, and economic consequences. There is still no sufficiently effective treatment of the consequences of TBI. Therefore, it is vital to create new agents with neuroprotective properties for correcting neurological disturbances caused by TBI.
We used the modified model of focal brain damage in rats (Feeney et al., 1981). For trauma creation, over the trephine opening, drilled in the left frontal skull part over sensomotor zone of cerebral cortex, the movable teflon footplate with a diameter 4 mm and a course of 2,5 mm was placed, and on this weight 50 g load stroked after fall down along the guiding rail. Neurological deficit was evaluated in “limb placing” test on the 3d and 7th day after trauma. Primary culture rat cerebellar granulle neurons (CGNs) were prepared from cerebella of 6–7-day-old Wistar rats. Cultures were utilized for experiments after 7–8 days of cultivation. CGNs were exposed to 0,5-1,5 mg/l GK-2 for 24h in medium. Oxidative stress was induced by addition for 20 min to 0.15 mM H2O2 containing balanced salt.
The results of the limb-placing test revealed the development after the trauma of a functional deficit in the right limbs, whereas it was absent in the left limbs. In the intact rats before the trauma, the test gave 12 points for both the right and left limbs, and after the skull–brain trauma in the rats not treated with GK-2 this score for the right
limbs was 6.1± 0.9 points on the third day (n= 16) and 6.3± 0.7 points on the seventh day (n= 16). The intraperitoneal injections of GK-2 significantly decreased the neurological deficit. In this case the right limbs of the rats showed on the third day 8.2± 0.1 (n= 17) and 9± 0.7 points (n= 17) on the seventh day after the trauma. GK-2 protects CGNs against H2O2-induced apoptosis. Quantitative analysis of the experimental data showed that 34 ± 3.6% of the neurons survived in the presence of H2O2, but if the CGNs were treated GK-2 (0.5, 1, 1.5 mg/l) survival increased to 44±3.7%, 48±4.6% and 53±4.2% respectively. Therefore, our findings on the possibility of curing trauma using GK-2, dipeptide mimetic of NGF are very promising for further studies of the pharmacological potential of the preparations.
This study was supported by RFBR grants 12-04-00025-а and 11-04-00360-a.