Effects of enoxaparin on parameters of oxidative stress, inflammation and neuroprotection in the rat parietal cortex following traumatic brain injury

K Pilipovic1, Ž Župan2,3, G Župan1. 1University of Rijeka, Faculty of Medicine, Department of Pharmacology, Croatia, 2University of Rijeka, Faculty of Medicine, Department of Anesthesiology, Reanimatology and Intensive Care Medicine, Croatia, 3Clinical Hospital Center Rijeka, Clinics of Anesthesiology and Intensive Care Medicine, Croatia

Traumatic brain injury (TBI) causes both an acute neuronal damage as well as progressive injury through detrimental processes such as oxidative stress and inflammation. Enoxaparin, low molecular weight heparin, significantly reduces the brain contusion and edema, and improves the functional outcomes in the experimental TBI. We have previously shown that enoxaparin protects the hippocampus following TBI by reducing oxidative damage and inflammation in that brain structure. Therefore, the purpose of this study was to investigate the effects of enoxaparin on some parameters of oxidative stress, inflammation and neuroprotection in the parietal cortex after brain trauma in the rat.

Experiments were performed on adult male Wistar rats (n = 5 per group). TBI of moderate severity was performed over the left parietal cortex using the lateral fluid percussion brain injury model. Animals were s.c. injected with either enoxaparin (1 mg/kg) or vehicle 1, 7, 13, 19, 25, 31, 37, and 43 h after the TBI induction. Sham-operated, vehicle-treated animals were used as the control group. All rats were sacrificed 48 h after the induction of TBI. The cortices were processed for Western blotting analyses of the oxidized protein levels, as well as the expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitory kappa B alpha (IκBα), heat shock protein 70 (HSP70), precursor and mature form of brain derived neurotrophic factor (BDNF). The results were analyzed by one-way ANOVA and p < 0.05 was considered to be statistically significant.

TBI caused a significant increase in the oxidized protein levels, upregulated COX-2 and IκBα expressions, reduced the protein amount of the precursor BDNF, but it did not influence iNOS, HSP70 and the mature BDNF expressions. Enoxaparin treatment significantly decreased the COX-2 overexpression and additionally upregulated the expression of IκBα, while it had no effect on the protein oxidative damage or the lowered expression of the BDNF precursor.

Our results suggest that neuroprotective effects of enoxaparin in the parietal cortex following experimental TBI could be the result of its antiinflammatory actions.