Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model.

OBJECTIVE: This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. METHODS: This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. RESULTS: G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. CONCLUSION: In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

Effects of the Calcium Channel Blocker Otilonium Bromide on Seizure Activity in Rats With Pentylenetetrazole-Induced Convulsions.

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25 mg/kg and 50 mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2 s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5 nmol/gr to 51.09 nmol/gr (lower-dose), 33.2 nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.

Effects of the Prenatal Administration of Tetanus Toxoid on the Sociability and Explorative Behaviors of Rat Offspring: A Preliminary Study.

OBJECTIVE: Autism spectrum disorder (ASD) is a severely disabling psychiatric disease characterized by impairments in communication and social skills. Although efforts have been made to explore the etiology of ASD, its pathophysiology remains unclear. This issue is rendered more challenging by confounding data about the effects of vaccination on disease etiology. In this study, therefore, we investigated the neurodevelopmental effects of maternal tetanus toxoid administration on rat offspring. We hypothesized that the vaccine affects the sociability and preference for social novelty of rat offspring as well as the production of immunological and neurotrophic factors, including tumor necrosis factor-alfa (TNF-α), neuregulin-1 (NRG-1), neuron growth factor (NGF), and oxytocin. METHODS: The study involved 12 female and 4 male adult Sprague-Dawley rats (238 ± 10 g), which were assigned to two groups. Group 1 (control group) was given 0.5 ml of normal saline (0.9% NaCl) on the 10th day of pregnancy, whereas Group 2 (experimental group) was administered 0.5 ml of tetanus vaccine (tetanus toxoid, 40 IU). RESULTS: Maternal tetanus toxoid administration exerted beneficial effects on the sociability and explorative behaviors of the rats. The brain tissue levels of TNF-α, NGF, NRG-1, and oxytocin were higher in the experimental group than those among the controls. All these significant differences were found in both the male and female rats. CONCLUSION: This study is the first to demonstrate the advantages of tetanus toxoid administration in relation to the sociability and explorative behaviors of rat offspring. The results showed that the vaccine also influences NRG-1, neuregulin, and oxytocin production.

Effect of Lipid Emulsion on the Improvement of Renal Damage in Colistin- Induced Nephrotoxicity.

BACKGROUND: Colistin utilization has gradually increased worldwide with the rising of multidrug-resistant (MDR) gram-negative bacilli despite its nephrotoxicity. Lipid emulsion (LE) is widely used for the toxic overdose treatment of various drugs. OBJECTIVE: The aim of the present study is to evaluate the effect of lipid emulsion on the improvement of renal damage in colistin-induced nephrotoxicity with an experimental Sprague Dawley rat model. METHODS: Twenty-four male Sprague Dawley rats were initially assigned to 2 random groups. Sixteen rats were given a single dose of 20 mg/kg colistin, and eight rats received no medication (control group). Sixteen rats that were administered colistin were sub-divided into 2 groups. Group 1/LE rats (n = 8) were given 20 ml/kg solution of lipid emulsion, and group 2/S rats (n = 8) were given 20 ml/kg/day (i.p.) of 0.9% NaCl saline; both were administered for 10 days. Then tubular injury was evaluated histopathologically. Serum levels of blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), and creatinine were measured. Besides, malondialdehyde (MDA) levels were determined in tissue samples for the assessment of lipid peroxidation. RESULTS: The mean percent of tubular epithelial cell injury and tubular dilatation was found significantly higher in group 2/S than in control and group 1/LE (p < 0.0001 and < 0.001; respectively). KIM-1 and MDA levels were also statistically higher in group 2/S than in control and group 1/LE. (p < 0.0001 and < 0.0001; respectively). Additionally, serum BUN and creatinine levels of group 2/S were significantly greater than control and group 1/LE (p < 0.0001 and < 0.0001; respectively). CONCLUSION: In this present study, we determined that colistin-induced proximal tubular damage was decreased histopathologically and serologically by the effect of lipid emulsion. Thus, our findings may guide future studies on the clinical use of colistin, particularly in MDR positive intensive care infections.

Papaverine Has Therapeutic Potential for Sepsis-Induced Neuropathy in Rats, Possibly via the Modulation of HMGB1-RAGE Axis and Its Antioxidant Prosperities.

AIM: Our aim was to investigate the possible neuroprotective properties of papaverine in sepsis-induced critical illness neuropathy (SCIN) through the evaluation of various inflammatory biochemical markers, including interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), and oxidative stress biomarkers, such as malondialdehyde (MDA) and lactic acid. Additionally, evaluation of the HMGB1/RAGE interactions in SCIN was another target of this research. METHOD: To create a sepsis model, a procedure involving intraperitoneal injection of feces was performed on 48 rats. The rats were divided into four equal groups: sham operated, controls and those receiving 20 and 40 mg/kg/day papaverine. After five-day treatments, compound muscle action potential (CMAPs) with electroneuromyography (ENMG) was recorded in all rats. Following ENMG evaluations, the plasma levels of sRAGE, HMGB1, TNF-α, IL-6, CRP, MDA and lactic acid were measured. RESULTS: TNF-α, CRP, IL-6, HMGB1, MDA, and lactic acid levels were significantly elevated in the SCIN group, and sRAGE levels were significantly decreased. In recipients of papaverine (20 and 40 mg/kg) treatment, these biochemical findings were improved. Furthermore, electrophysiological findings also showed significant improvement in both 20 and 40 mg/kg papaverine treated groups. CONCLUSION: Papaverine demonstrates neuroprotective effects in a rat model of SCIN. Considering its anti-inflammatory and antioxidant properties, papaverine's neuroprotective effects possibly stem from the suppression of the RAGE-HMGB1 axis.

Beneficial Effects of Ibuprofen on Pentylenetetrazol-induced Convulsion.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used as an anti-inflammatory, anti-pyretic, and analgesic. Although some studies have focused on the anti-inflammatory and anti-pyretic properties of ibuprofen during febrile convulsions, only one has investigated its antiepileptic effects. In the present study, we aimed to investigate the effects of ibuprofen in rats exposed to pentylenetetrazol (PTZ)-induced seizures. In total, 48 rats were randomly divided in two groups: Group A for electroencephalography (EEG) recordings and Group B for behavioral assessment. All EEG recordings and behavioral assessment protocols were performed. In addition, groups were compared in terms of prostaglandin F2 alfa (PGF2α) levels in the brain. We demonstrated the beneficial effects of the administration of ibuprofen in PTZ-induced seizures in rats via the following findings: spike percentages and Racine convulsion scale values were significantly lower and first myoclonic jerk (FMJ) onset times were significantly higher in the ibuprofen-administered groups. Moreover, PGF2α levels in the brain were significantly higher in the saline and PTZ 70 mg/kg group than in the control and PTZ 70 mg/kg and 400 mg/kg ibuprofen groups. Our study is the first to demonstrate the beneficial effects of ibuprofen on seizures through behavioral, EEG, and PGF2α brain assessments. Ibuprofen can be used for epilepsy and febrile seizures safely and without inducing seizures. However, further experimental and clinical studies are needed to confirm our results.

Protective effect of oxytocin on a methotrexate-induced ovarian toxicity model.

PURPOSE: Although cancer predominantly affects people at older ages, a substantial number of patients, like breast cancer patients, are diagnosed before they have completed their families or even before giving birth. Furthermore, cytotoxic chemotherapy may be required in addition to treat cancer survivors. The present study was conducted to investigate the protective effect of oxytocin (OT) on methotrexate (MTX)-induced ovarian toxicity in rats. METHODS: Eighteen adult female Sprague-Dawley rats were used in the study. All rats were divided randomly into three groups. The control group (n = 6) received no treatment. The remaining 12 rats received a single dose of 20 mg/kg of MTX. Half of the rats (n = 6) were treated with 1 mg/kg/day of saline, and the other half (n = 6) were treated with 160 µg/kg/day of OT for 21 days. Then, blood samples were collected for biochemical analysis, and an ovariectomy was performed for histopathological examination. RESULTS: Plasma malondialdehyde (MDA) and transforming growth factor-ß (TGF-ß) levels were significantly lower in the MTX + OT group compared to the MTX + saline group (p = 0.000036 for MDA; p = 0.0044 for TGF-ß). AMH levels were also significantly higher in the MTX + OT group than in the MTX + saline group (p = 0.000036). The ovarian fibrosis percent was also notably lower in the MTX + OT group than in the MTX + saline group (p = 0.000036). CONCLUSION: On the basis of these findings, OT is a promising agent for ameliorating harmful effects of MTX on rat ovaries in an experimental model.

Atorvastatin has therapeutic potential for the fatty liver-induced memory dysfunction in rats, likely via its antioxidant and anti-inflammatory properties.

This study aimed to evaluate the memory function in a rat model of fatty liver and to investigate the effects of statins on fatty liver, neuronal inflammation, oxidative stress and memory. In this study, 24 male rats were used and were divided into four groups consisting of 6 animals in each. Of them, 12 rats received liquid diet containing 35% fructose for 8 weeks in order to induce hepatosteatosis, while other animals had a normal nutrition. Group 1 served as controls and had a normal nutrition with no drug treatment. The animals in Group 2 had a normal nutrition and treated with atorvastatin. Group 3 received high-fructose diet with no drug treatment and Group 4 received high-fructose diet followed by atorvastatin treatment. After the two weeks of treatment period, passive avoidance tasks evaluating the memory were performed in both the study and control groups. The liver and brain were then removed for histologic, pathologic, and biochemical evaluation. In the non-treated rats with hepatosteatosis (Group 3), the lowest mean latency time and the highest mean histopathologic liver score, and brain TNF- α and MDA (Measurement of lipid peroxidation) were found (p < 0.00001). On the other hand, in the animals treated with atorvastatin, all these parameters were significantly higher than that of controls and significantly lower than that of Group 3 (p < 0.05). Fatty liver can increase inflammation and cause memory disorders, and atorvastatin may have a positive effect on cognitive disorders.