Objectives The purpose of this PhD thesis was to study: a) the degree of lipid and protein oxidative damage, antioxidant enzymes’ (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) activities, the expressions of different proteins (proinflammatory factors COX-2 and iNOS, an NFB signaling pathway inhibitor IB, and the endogenous neuroprotective proteins, BDNF and HSP70), and water content in different brain structures, as well as b) the effects of pioglitazone (PPAR agonist) and enoxaparin (low molecular weight heparin) on the tested parameters of oxidative stress and the expressions of the aforementioned proteins in rats with traumatic brain injury (TBI). Material and Methods Brain trauma of moderate severity was induced using the lateral fluid percussion injury model in the area of left parietal cortex. Levels of lipid peroxidation products, as well as the activities of SOD and GSH-Px in tissue homogenates were determined by spectrophotometry. The degree of protein oxidative damage (protein carbonyl content), and the levels of different proteins’ expressions were determined using the Western blot method. In one part of the research, histological and immunohistological methods were used. Hematoxylin-eosin and cresyl violet stainings were used for the detection of the tissue damage extent. Regional distributions of COX-2 and HSP70 expressions were analyzed by immunohistochemistry. With the intent to investigate oxidative damage, inflammation, the expressions of different proteins, in various brain regions following traumatic injury, animals were sacrificed 24 h after the TBI induction. Animals of the control group were subjected to the sham TBI. A part of the animals were sacrificed 48 h after TBI in order to determine the existence of posttraumatic brain edema. In the part of the research, in which the effects of pioglitazone were investigated, injured animals were treated with single dose of the tested glitazone (1 or 3 mg/kg) or by vehicle (dimethyl sulfoxide), 10 min after the TBI induction. Rats of the control group were handled identically, except that they were not subjected to TBI. Animals used in this part of the research were sacrificed 24 h following TBI onset. In the part of the research which was focused on the effects of enoxaparin in TBI, experimental animals were treated with the tested drug (1 mg/kg) or with vehicle (water for injections) 1 h after the TBI induction, and additionally with 7 more doses applied every 6 h after the first dose. All rats of this part of the study were sacrificed 48 h after the TBI induction. Animals of the control group were sham injured, and, instead of enoxaparin, they were injected with appropriate vehicle. Results TBI of moderate severity caused the most prominent brain damage in the rat area of parietal cortex and hippocampus. In the mentioned brain structures, increased levels of the lipid peroxidation products, protein carbonyls and the COX-2 expressions after TBI were detected. Increased GSH-Px activities in both mentioned structures were recorded. COX-2 protein expressions were also augmented in the thalamus and in the entorhinal cortex of the injured rats. Additionally, following the brain injury, in the hippocampus, the iNOS, IB, and proBDNF expressions were increased, while the mBDNF expression was decreased. In the parietal cortex decreased expressions of the IB and HSP70 were detected. In the entorhinal cortex, the proBDNF expression was increased. Furthermore, in the thalamus, increased expressions of iNOS and IB were detected. Brain edema caused by TBI was recorded in the ipsi- and contralateral parietal cortex, ipsilateral hippocampus, and cerebellum. Effects of pioglitazone and enoxaparin were tested in the parietal cortex and the hippocampus of the injured rats. It was established that the effects of pioglitazone, in the TBI model used, were dose-, and the brain structure-related. Pioglitazone can reduce oxidative lipid and protein damage, increase the GSH-Px activity, reduce the iNOS, and increase the proBDNF and mBDNF expressions. Enoxaparin, in the experimental conditions used, was neuroprotective in both brain structures tested. In the parietal cortex of injured animals, enoxaparin increased the GSH-Px activity and the IB expression, and decreased the COX-2 expression. In the hippocampus of rats with TBI, it reduced oxidative lipid and protein damage, and also attenuated injury-induced increase in the COX-2 protein expression. Conclusion TBI causes prominent oxidative and inflammatory damage of the parietal cortex and hippocampus in rats. Changes of some proinflammatory and endogenous neuroprotective proteins were recorded in the other brain structures tested following brain trauma. Pioglitazone and enoxaparin could be neuroprotective in experimental TBI.