In vivo studies of the therapeutic effects of argon in traumatic brain injury (TBI) are limited, and their results are contradictory. The aim of this study was to evaluate the effect of a three-hour inhalation of argon (70%Ar/30%O₂) after an open TBI on the severity of the neurological deficit and the degree of brain damage in rats. The experiments were performed on male Wistar rats (n = 35). The TBI was simulated by the dosed open brain contusion injury. The animals were divided into three groups: sham-operated (SO, n = 7); TBI + 70%N2/30%O₂ (TBI, n = 14); TBI + 70%Ar/30%O₂ (TBI + iAr, n = 14). The Neurological status was assessed over a 14-day period (using the limb-placing and cylinder tests). Magnetic resonance imaging (MRI) scans and a histological examination of the brain with an assessment of the volume of the lesions were performed 14 days after the injury. At each of the time points (days 1, 7, and 14), the limb-placing test score was lower in the TBI and TBI + iAr groups than in the SO group, while there were no significant differences between the TBI and TBI + iAr groups. Additionally, no differences were found between these groups in the cylinder test scores (day 13). The volume of brain damage (tissue loss) according to both the MRI and histological findings did not differ between the TBI and TBI + iAr groups. A three-hour inhalation of argon (70%Ar/30%O₂) after a TBI had no neuroprotective effect.

This is the first in vivo study to investigate the neuroprotective effects of krypton on focal cerebral ischemia. The aim of the study was to analyze the effect of 2 h of inhalation of a krypton–oxygen mixture (Kr 70%/O₂ 30%) on the recovery of neurological functions and the degree of brain damage in rats after photoinduced ischemic stroke (PIS) and to investigate the possible mechanisms responsible for this neuroprotection. Experiments were performed on male Wistar rats weighing 250–300 g (n = 32). Animals were randomized into four groups. Two groups (n = 20) underwent photoinduced ischemic stroke, followed by 2 h of inhalation of krypton–oxygen mixture consisting of Kr 70%/O₂ 30% or a nitrogen–oxygen breathing mixture consisting of N₂ 70%/O₂ 30%, followed by neurological examinations on days 3 and 7. The other two groups (n = 12) received only gas mixtures of the same concentration and exposure duration as in those in the PIS groups, then Western blot analysis of the potential molecular mechanisms was performed. The results of the study show that treatment with the krypton–oxygen mixture consisting of Kr 70%/O₂ 30% improves the neurological status on day 7 of observation, reduces the lesion volume according to the MRI examination and the number of Iba-1- and caspase-3-positive cells in the damaged area, promotes the activation of neoangiogenesis (an increase in the von Willebrand factor), and reduces the penumbra area and the number of NeuN-positive cells in it on day 14 of observation. Inhalation of the krypton–oxygen mixture also significantly increases the levels of phosphorylated AKT kinase (protein kinase B) and glycogen synthase kinase 3b (pGSK3b) and promotes the expression of transcription factor Nrf2, which was accompanied by the lowered expression of transcription factor NFkB (p50). Thus, we showed pronounced neuroprotection induced by krypton inhalation after stroke and identified the signaling pathways that may be responsible for restoring neurological functions and reducing damage.

The aim of the study was to compare the effect of sevoflurane and chloral hydrate on the neurological status and volume of brain damage after trauma and ischemia in experimental models of traumatic brain injury (TBI) and focal ischemic stroke (IS) induced by photothrombosis (PT).Materials and methods. The experiments were performed on mongrel Wistar rats weighing 250–300 g (N=43). There were 4 groups: the Ischemia + Sevoflurane group (ISSEV) (N=10), the Ischemia + Chloral hydrate group (ISCH) (N=10), TBI + Sevoflurane group (TBISEV) (N=13), and TBI+Chloral hydrate group (TBICH) (N=10). Ischemic brain damage was modelled using Rose Bengal (RB) dye-induced PT, and TBI was modelled using mechanical force-induced concussion.Results. MRI findings indicate lower volumes of brain damage (mm³) in rats from TBISEV group compared with the TBICH group (19±5 vs. 60±5, P<0.0001), and in the ISSEV group compared with the ISCH group (9.8±1.5 vs. 21.5±2, P=0.0016). Moreover, there was a significant difference between ISSEV and ISCH groups based on the protocol assessment of neurological status on day 14 with higher scores in ISSEV (11.4±1.8 vs. 4.9±2.6, P<0.0001).Conclusion. Taking into account the data obtained, we recommend a careful choice of anesthesia when modeling ischemic stroke and traumatic brain injury in animals. In particular, the neuroprotective effect of sevoflurane should be taken into account in the PT and TBI models.

Aim of the study. To determine the effects of xenon exposure at a dose of 0.5 MAC of different duration on the content and enzyme-inactivating phosphorylation of the glycogen synthase kinase-3β (GSK3β) in the perifocal zone of ischemic cerebral infarction in an experimental setting.Materials and methods. The Long method was used for modelling brain ischemia/reperfusion in 39 rats weighing 300-350 g. Study group animals was exposed to xenon at a dose of 0.5 MAC during 30, 60 and 120 minutes whereas control group animals received an oxygen-air mixture. Sham-operated animals served as a comparison group. The levels of GSK3β and phospho-GSK3β in brain homogenates were determined by blotting using specific antibodies.Results. In ischemic stroke model, the content of GSK3β did not significantly change in control animals compared to comparison group. However, control group animals exhibited significant (2.7-fold, P<0.001) decrease in the content of its phospho-GSK3β in the perifocal zone of ischemic cerebral infarction. Inhalation of 0.5 MAC xenon during 30 minutes did not lead to an increase in phosphorylation of the GSK3β enzyme (P=0.9), however, 60 and 120 minutes of 0.5 MAC xenon exposures resulted in the increase in phosphorylated form of the enzyme by a factor of 2.1 (P=0.005) and 2.3 (P=0.001), respectively, compared to the control group.Conclusion. The results reveal a possible molecular mechanism (i. e., execution of neuroprotective and anti-inflammatory effects of xenon due to GSK-Зβ inactivation) and show the prospects for using 60 and 120 minutes of 0.5 MAC xenon exposures in ischemic brain damage after a stroke, traumatic brain injury and other brain lesions.

The noble gas argon is one of the most promising neuroprotective agents for hypoxic-reperfusion injuries of the brain. However, its effect on traumatic injuries has been insufficiently studied. The aim of this study was to analyze the effect of the triple inhalation of the argon-oxygen mixture Ar 70%/O₂ 30% on physical and neurological recovery and the degree of brain damage after traumatic brain injury and to investigate the possible molecular mechanisms of the neuroprotective effect. The experiments were performed in male Wistar rats. A controlled brain injury model was used to investigate the effects of argon treatment and the underlying molecular mechanisms. The results of the study showed that animals with craniocerebral injuries that were treated with argon inhalation exhibited better physical recovery rates, better neurological status, and less brain damage. Argon treatment significantly reduced the expression of the proinflammatory markers TNFα and CD68 caused by TBI, increased the expression of phosphorylated protein kinase B (pAKT), and promoted the expression of the transcription factor Nrf2 in intact animals. Treatment with an argon-oxygen breathing mixture after traumatic brain injury has a neuroprotective effect by suppressing the inflammatory response and activating the antioxidant and anti-ischemic system.

INTRODUCTION: Severe combined trauma remains the leading cause of mortality and disability of the workable population. Under damaging factor influence, a whole cascade of pathological processes is triggered, leading to development of multiple organ failure. OBJECTIVE: Exploration of the effects synthetic analogue of tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine diacetate (Dalargin) on the dynamics of oxidative stress markers in patients with severe polytrauma and the development of organ dysfunction. MATERIALS AND METHODS: 104 patients with severe combined trauma were included in study. There were 38 patients in the Dalargin group and 66 patients in the control group. Patients from main group received Dalargin in the form of a constant infusion through a syringe dispenser at the dose of 10 mcg/kg/hour at first 12 hours of hospitalization and 5 mcg/kg/hour up to 72 hours from the moment of admission. The control group received standard treatment. Indicators of oxidative stress were evaluated at the time of admission (0 days), 1, 3, 5, 7, 10 and 14 days from the therapy onset. RESULTS: In the main group, there was a significant decrease in oxidative stress markers such as malondialdehyde from the first day of treatment (p < 0.05), normalization of stable nitric oxide metabolites at day 10, and a decrease in total antioxidant activity below normal throughout the observation period. Mortality was comparable in both groups (p > 0.05), but the length of hospital stay was lower in surviving patients in the Dalargin group (p < 0.05). The development of organ dysfunction (acute respiratory distress syndrome, acute kidney injury) was less frequent in the Dalargine group (p < 0.05), but infectious complications (pneumonia, meningitis, wound suppuration) were comparable. CONCLUSIONS: Dalargin leads to a decrease of oxidative stress markers and normalization of endothelial function indicators, which contributes to a decrease of organ dysfunction frequency.