Amelioration of propionic acid-induced autism spectrum disorder in rats through dapagliflozin: The role of IGF-1/IGFBP-3 and the Nrf2 antioxidant pathway.

The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder.

Hydroxychloroquine attenuates sepsis-induced acute respiratory distress syndrome in rats.

BACKGROUND: This study investigates the effects of hydroxychloroquine (HCQ) on a sepsis-induced acute respiratory distress syndrome (ARDS) model in rats, initiated by a fecal intraperitoneal injection procedure (FIP). METHODS: Three groups were established: control (n=8), FIP + saline (n=7), and FIP + HCQ (20 mg/kg/day) (n=9). Blood samples were collected for arterial blood gas and biochemical analyses, and bilateral pneumonectomy was performed for histopathologic examination. RESULTS: In the FIP + saline group, PaO2 decreased and PaCO2 increased, whereas these levels normalized in the FIP + HCQ group compared to the control (p<0.001 and p<0.05, respectively). Histopathological scores for alveolar congestion, perivascular/interstitial edema, hemorrhage in alveolar tissue, leukocyte infiltration or aggregation in air spaces/vascular walls, and alveolar wall/hyaline membrane thickness increased in the FIP + saline group compared to the control group (p<0.01). These scores decreased in the FIP + HCQ group compared to the FIP + saline group (p<0.01). HCQ reversed the sepsis-induced increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and lactic acid. CONCLUSION: HCQ may be an effective and safe option to mitigate the severe progression of ARDS.

Choline chloride shows gender-dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide-induced rat model of autism.

The neuroprotective effects of choline chloride, an essential nutrient, a precursor for the acetylcholine and synthesis of membrane phospholipids, have been associated with neurological and neurodegenerative diseases. Its contribution to autism spectrum disorder, a neurodevelopmental disorder, remains unknown. Thus, we aimed to evaluate the effects of choline chloride on social behaviours, and histopathological and biochemical changes in a rat autism model. The autism model was induced by administration of 100 µg/kg lipopolysaccharide (LPS) on the 10th day of gestation. Choline chloride treatment (100 mg/kg/day) was commenced on PN5 and maintained until PN50. Social deficits were assessed by three-chamber sociability, open field, and passive avoidance learning tests. Tumour necrosis factor alpha (TNF-α), interleukin-2 (IL) and IL-17, nerve growth factor (NGF), and glutamate decarboxylase 67 (GAD67) levels were measured to assess neuroinflammatory responses. In addition, the number of hippocampal and cerebellar neurons and glial fibrillary acidic protein (GFAP) expression were evaluated. Social novelty and passive avoidance learning tests revealed significant differences in choline chloride-treated male rats compared with saline-treated groups. TNF-α, IL-2, and IL-17 were significantly decreased after choline chloride treatment in both males and females. NGF and GAD67 levels were unchanged in females, while there were significant differences in males. Histologically, significant changes in terms of gliosis were detected in hippocampal CA1 and CA3 regions and cerebellum in choline chloride-treated groups. The presence of ameliorative effects of choline chloride treatment on social behaviour and neuroinflammation through neuroinflammatory, neurotrophic, and neurotransmission pathways in a sex-dependent rat model of LPS-induced autism was demonstrated.

The renoprotective effect of Tibolone in sepsis-induced acute kidney injury.

INTRODUCTION: Sepsis-induced acute kidney injury (AKI) remains a major challenge in intensive care, contributing significantly to morbidity and mortality. Tibolone, known for its neuroprotective and hormonal properties, has not been explored for its potential in AKI management. This study investigates the protective effects of Tibolone and its underlying mechanisms involving Sirtuin-1 (SIRT1) and Yes-Associated Protein (YAP) in a rat sepsis model. MATERIALS AND METHODS: Thirty-six female Wistar albino rats underwent cecal ligation and puncture (CLP) to induce sepsis. They were randomly assigned to control, CLP+Saline, and CLP+Tibolone groups. Tibolone was administered intraperitoneally. Biomarkers, including Sirtuin (SIRT1), Yes-associated protein (YAP), Tumor necrosis factor (TNF-α), High mobility group box 1 (HMGB1), malondialdehyde (MDA), creatinine, and urea, were assessed. Histopathological examination evaluated renal damage. RESULTS: Tibolone administration significantly reduced plasma TNF-α, HMGB1, MDA, creatinine, and urea levels compared to the CLP+Saline group. Moreover, Tibolone elevated SIRT1 and YAP levels in kidney tissues. Histopathological examination demonstrated a significant decrease in tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and interstitial inflammation in Tibolone-treated rats. CONCLUSION: This study unveils the protective role of Tibolone against sepsis-induced AKI in rats. The improvements in inflammatory and oxidative biomarkers and histological evidence suggest Tibolone's potential as a therapeutic intervention in sepsis-associated kidney injury. The upregulation of SIRT1 and YAP indicates their involvement in Tibolone's renoprotective mechanisms. Further investigations are warranted to explore Tibolone's translational potential in human sepsis-induced AKI.

Propionyl-l-carnitine mitigates ischemia-reperfusion injury in rat epigastric island flaps.

Background: Ischemia-reperfusion injury presents a substantial concern in various medical scenarios, notably in reconstructive surgery involving tissue flaps. Despite reports on the protective benefits of Propionyl-l-carnitine against ischemia-reperfusion injury, a thorough assessment of its efficacy in epigastric island flap models is currently lacking. Methods: Sixteen male Sprague-Dawley rats underwent epigastric island flap surgery and were divided into two groups: a Propionyl-l-carnitine group that received intraperitoneal Propionyl-l-carnitine prior to ischemia induction and a sham group that received saline treatment. A comprehensive evaluation was performed including macroscopic, biochemical and histological assessments encompassing measurements of flap survival areas, lipid peroxidation (malondialdehyde), glutathione, myeloperoxidase, nitric oxide and peripheral neutrophil counts. Results: The Propionyl-l-carnitine group demonstrated significantly increased flap survival areas when compared to the sham group. Administration of Propionyl-l-carnitine led to reduced malondialdehyde levels and elevated glutathione levels indicating a reduction in oxidative stress. Furthermore, the Propionyl-l-carnitine group exhibited lower myeloperoxidase levels, higher nitric oxide levels and reduced peripheral neutrophil counts, suggesting a decrease in the inflammatory response. Histopathological analysis revealed decreased levels of inflammation, necrosis, polymorphonuclear leukocyte infiltration and edema in the Propionyl-l-carnitine group. Additionally, vascularity was enhanced in the Propionyl-l-carnitine group. Conclusion: This study provides compelling evidence that Propionyl-l-carnitine administration effectively mitigates the deleterious effects of ischemia-reperfusion injury in epigastric island flaps. This is substantiated by the improved flap survival, diminished oxidative stress and inflammation, as well as the enhanced vascularity observed. Propionyl-l-carnitine emerges as a promising therapeutic intervention to enhance tissue flap survival in reconstructive surgery, warranting further exploration through larger-scale investigations.

Beneficial effects of IVIG treatment on experimental-induced osteoporosis.

Objective: Estrogen (E2) plays a significant role in postmenopausal osteoporosis, and its deficiency is related to chronic low-grade inflammation. Intravenous immunoglobulin (IVIG) is composed of immunoglobulins derived from the plasma of healthy donors. Numerous anti-inflammatory pathways are responsible for IVIG's anti-inflammatory action The aim of this study is to investigate the effects of IVIG on experimental-induced osteoporosis. Materials and methods: Forty adult female Wistar rats were included in the study. Thirty rats underwent bilateral dorsal ovariectomy. Rats were grouped as Group 1 (n = 10, ovariectomy and saline); Group 2 (n = 10, ovariectomy and E2); Group 3 (n = 10, ovariectomy and IVIG), and Control group (n = 10, no oophorectomy). Histopathological examination of bone tissue, and biochemical analysis for beta-catenin, plasma Tumor Necrosis Factor-α, IL-6, receptor activator of nuclear-κB ligand (RANKL), and osteoprotegerin (OPG) levels were made. Results: The IVIG group had increased trabecular number, area, and thickness with increased bone mineral density as well as decreased trabecular separation compared with the saline group. IVIG group had lower serum RANKL and higher serum OPG levels when compared with the saline group. The bone marrow beta-catenin level was significantly higher in the control and ovariectomy + IVIG groups. Conclusion: IVIG has beneficial effects on experimentally induced osteoporosis with a possible action on inflammation and RANKL-ß-catenin pathway.

Objetivo: El estrógeno juega un papel importante en la osteoporosis posmenopáusica y su deficiencia está relacionada con la inflamación crónica de bajo grado. La inmunoglobulina intravenosa (IGIV) está compuesta por inmunoglobulinas derivadas del plasma de donantes sanos. El objetivo de este estudio es investigar los efectos de IVIG en la osteoporosis inducida experimentalmente. Materiales y métodos: 30 ratas se sometieron a ovariectomía dorsal bilateral. las ratas se agruparon como: Grupo 1 (n = 10, ovariectomía y solución salina); Grupo 2 (n = 10, ovariectomía y estrógeno); Grupo 3 (n = 10, ovariectomía e IVIG) y Grupo Control (n = 10, sin ovariectomía). Se realizó un examen histopatológico del tejido óseo y un análisis bioquímico de los niveles de beta-catenina, factor de necrosis tumoral α (TNF-α), IL-6, RANKL y osteoprotegerina (OPG) en plasma. Resultados: El grupo IVIG había aumentado el número, el área y el grosor trabecular con una mayor densidad mineral ósea, así como una menor separación trabecular en comparación con el grupo de solución salina. El nivel de beta-catenina en la médula ósea fue significativamente mayor en los grupos de control y de ovariectomía + IVIG. Conclusión: IVIG tiene efectos beneficiosos sobre la osteoporosis inducida experimentalmente con una posible acción sobre la inflamación y la vía RANKL-ß-catenina.

Oxidative stress and inflammatory markers in streptozotocin-induced acute and subacute toxicity response.

Streptozotocin (STZ) is used as a diabetes-inducing agent in experimental animal studies. However, it is known that STZ-induced diabetic animals show significant increases in oxidative stress parameters and neurodegeneration besides their blood glucose level. In this study, the acute and subacute toxic effects of STZ on the liver, sciatic nerve, and brain tissues were investigated in vivo rat model. Sprague-Dawley rats were divided into two groups; while 50 mg/kg STZ was administered ip to the STZ group, only saline was administered to the control group. After STZ administration, three units (100 U/mL) of subcutaneous insulin glargine were applied daily to prevent the formation of diabetes. At 24 h, 1,2, and 4 weeks after applications, rats from each group were sacrificed and tissues were removed under anesthesia. At the end of the study, compared to the control, a significant decrease in SOD and GST activity and an increase in lipid peroxidation were detected in the liver and sciatic tissues of rats in the STZ-treated group in the first 24h. Considering the TUNEL, NFκB, and NOS2 expressions, it was noted that while the effects of STZ on the liver were observed in the acute stage (24h), it had subacute effects on the brain. When apoptosis-related gene expression (Bcl-2, Bax, CASP3, CASP8, CASP9, TNF-α) and immunohistochemistry were evaluated, the apoptotic effect of STZ was observed mostly in sciatic nerve tissues. Within the scope of the study, it was revealed that STZ did not only show selective toxicity to pancreatic ß cells but also very toxic to other tissues and organs.

Prenatal Exposure to COVID-19 mRNA Vaccine BNT162b2 Induces Autism-Like Behaviors in Male Neonatal Rats: Insights into WNT and BDNF Signaling Perturbations.

The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential.

Evaluation of the Reparative Effect of Sinomenine in an Acetaminophen-Induced Liver Injury Model.

Due to its rising global prevalence, liver failure treatments are urgently needed. Sinomenine (SIN), an alkaloid from sinomenium acutum, is being studied for its liver-repair properties due to Acetaminophen (APAP) overdose. SIN's effect on APAP-induced hepatotoxicity in rats was examined histologically and biochemically. Three groups of 30 adult male Wistar rats were created: control, APAP-only, and APAP + SIN. Histopathological and biochemical analyses were performed on liver samples after euthanasia. SIN is significantly protected against APAP damage. Compared to APAP-only, SIN reduced cellular injury and preserved hepatocellular architecture. The APAP + SIN Group had significantly lower ALT, MDA, and GSH levels, protecting against hepatocellular damage and oxidative stress. SIN also had dose-dependent antioxidant properties. When examining critical regulatory proteins, SIN partially restored Sirtuin 1 (SIRT1) levels. While BMP-7 levels were unaffected, histopathological evidence and hepatocyte damage percentages supported SIN's liver-restorative effect. SIN protected and repaired rats' livers from APAP-induced liver injury. This study suggests that SIN may treat acute liver damage, warranting further research into its long-term effects, optimal dosage, and clinical applications. These findings aid liver-related emergency department interventions and life-saving treatments.

The Effect of Liraglutide on Axon Regeneration and Functional Recovery after Peripheral Nerve Lesion.

Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational research efforts. Thirty adult Wistar rats underwent sciatic nerve dissection and repair surgery. The nerves were surgically transected using micro scissors at a precise location located 1.5 cm proximal to the trifurcation site. The study included a control group and two experimental groups, one treated with saline (placebo group) and the other with liraglutide (experimental group) for 12 weeks. Motor function, electromyography (EMG), and biochemical and histopathological analyses were performed after 12 weeks of treatment. Electrophysiological assessments revealed that liraglutide improved the compound muscle action potential (CMAP) amplitude and motor function compared to the saline-treated group. Histological and immunohistochemical analyses demonstrated increased NGF expression, total axon number, and diameter and reduced fibrosis in the liraglutide group. Biochemical analyses illustrated liraglutide's antioxidative properties, evidenced by reduced malondialdehyde (MDA) levels. Galectin-3 levels were suppressed and GDF-11 levels were modulated by liraglutide, indicating anti-inflammatory and anti-apoptotic effects. Liraglutide is a promising therapeutic intervention for peripheral nerve injuries, promoting functional recovery and histopathological improvement. Its multifaceted positive impact, beyond glycemic control, suggests constructive effects on the acute and chronic inflammatory processes associated with peripheral neuropathy. These findings warrant further research to elucidate molecular mechanisms and facilitate clinical translation. The study contributes valuable insights to the growing understanding of GLP-1 receptor agonists' neuroprotective properties in the context of peripheral nerve injuries.

Neuroprotective effect of dexpanthenol on rotenone-induced Parkinson's disease model in rats.

Parkinson's disease (PD) is the second most common and progressive neurodegenerative disease. This experimental study was designed to investigate the neuroprotective effects of dexpanthenol on antioxidant and anti-inflammatory processes in a rotenone-induced Parkinson's disease model in rats. Twenty-one male rats were randomly divided into 2 groups. The rotenone group (n = 14) was administered rotenone by intrastriatal injection, and the vehicle group (n = 7) was administered DMSO with the same application route. All animals underwent rotational movement testing with apomorphine injection 10 days later. Those with Parkinson's disease model were randomly divided into 2 groups. While 1 ml/kg of saline was applied to the saline group (n = 7), 500 mg/kg was administered to the dexpanthenol group intraperitoneally for 28 days. After 28 days, all rats were euthanized and brain tissue was removed. While striatal areas were evaluated immunohistochemically, brain MDA, TNF-α, and HVA levels were measured to evaluate their anti-oxidative and anti-inflammatory effects. In the dexpanthenol group, the total count (p < 0.001) and intensity (p < 0.001) of dopaminergic neurons in the striatal areas increased compared to the saline group. It was revealed that MDA (nmol/g) (p < 0.001) and TNF-α (pg/g) (p < 0.001) levels decreased in the dexpanthenol group, while HVA (ng/mg) levels increased (p < 0.01). This study suggests that dexpanthenol may have a neuroprotective effect by reducing neuronal loss, oxidative damage, and neuroinflammation in the striatum in rats.

Autophagy and anti-inflammation ameliorate diabetic neuropathy with Rilmenidine.

PURPOSE: To evaluate the neuroprotective effects of Rilmenidine on diabetic peripheral neuropathy (DPN) in a rat model of diabetes induced by streptozotocin (STZ). METHODS: STZ (60 mg/kg) was administered to adult Sprague-Dawley rats to induce diabetes. On the 30th day after STZ administration, electromyography (EMG) and motor function tests confirmed the presence of DPN. Group 1: Control (n = 10), Group 2: DM + 0.1 mg/kg Rilmenidine (n = 10), and Group 3: DM + 0.2 mg/kg Rilmenidine (n = 10) were administered via oral lavage for four weeks. EMG, motor function test, biochemical analysis, and histological and immunohistochemical analysis of sciatic nerves were then performed. RESULTS: The administration of Rilmenidine to diabetic rats substantially reduced sciatic nerve inflammation and fibrosis and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves from saline-treated rats revealed increased perineural thickness, HMGB-1, tumor necrosis factor-α, and a decrease in nerve growth factor (NGF), LC-3. In contrast, Rilmendine significantly inhibited inflammation markers and prevented the reduction in NGF expression. In addition, Rilmenidine significantly decreased malondialdehyde and increased diabetic rats' total antioxidative capacity. CONCLUSIONS: The findings of this study suggest that Rilmenidine may have therapeutic effects on DNP by modulating antioxidant and autophagic pathways.

Prenatal SARS-CoV-2 Spike Protein Exposure Induces Autism-Like Neurobehavioral Changes in Male Neonatal Rats.

Recent research on placental, embryo, and brain organoids suggests that the COVID-19 virus may potentially affect embryonic organs, including the brain. Given the established link between SARS-CoV-2 spike protein and neuroinflammation, we sought to investigate the effects of exposure to this protein during pregnancy. We divided pregnant rats into three groups: Group 1 received a 1 ml/kg saline solution, Group 2 received 150 µg/kg adjuvant aluminum hydroxide (AAH), and Group 3 received 40 µg/kg spike protein + 150 µg/kg AAH at 10 and 14 days of gestation. On postnatal day 21 (P21), we randomly separated 60 littermates (10 male-female) into control, AAH-exposed, and spike protein-exposed groups. At P50, we conducted behavioral analyses on these mature animals and performed MR spectroscopy. Subsequently, all animals were sacrificed, and their brains were subject to biochemical and histological analysis. Our findings indicate that male rats exposed to the spike protein displayed a higher rate of impaired performance on behavioral studies, including the three-chamber social test, passive avoidance learning analysis, open field test, rotarod test, and novelty-induced cultivation behavior, indicative of autistic symptoms. Exposure to the spike protein (male) induced gliosis and neuronal cell death in the CA1-CA3 regions of the hippocampus and cerebellum. The spike protein-exposed male rats exhibited significantly greater levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and lactate and lower levels of brain-derived neurotrophic factor (BDNF) than the control group. Our study suggests a potential association between prenatal exposure to COVID-19 spike protein and neurodevelopmental problems, such as ASD. These findings highlight the importance of further research into the potential effects of the COVID-19 virus on embryonic and fetal development and the potential long-term consequences for neurodevelopment.

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model.

Peripheral nerve damage is a significant clinical problem with limited therapeutic options. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic approach due to their regenerative potential. However, the underlying mechanisms by which ADSCs promote peripheral nerve regeneration remain unclear. In this study, we investigated the role of syndecan-1 and heat shock protein 70 (HSP-70) in mediating the regenerative effects of ADSCs on peripheral nerves. ADSCs were characterized and isolated from the adipose tissue of rats. In vitro experiments were conducted to evaluate the ability of ADSCs to secrete syndecan-1 and HSP-70 in response to stress conditions. To evaluate the therapeutic potential of ADSCs, rats with sciatic nerve injuries were treated with ADSCs and assessed for functional recovery, nerve regeneration, and changes in syndecan-1 and HSP-70 levels. Regeneration was evaluated with Electromyography (EMG) histology. The results showed that ADSCs could secrete syndecan-1 and HSP-70 in response to stress conditions. Furthermore, ADSC treatment significantly improved functional recovery and nerve regeneration and increased syndecan-1 and HSP-70 levels in the injured nerve. On the other hand, ADSCs make improvements histologically through the influence of Nerve growth factor (NGF), Malondialdehyde (MDA), and EMG.

Demonstration of ameliorating effect of papaverine in sepsis-induced acute lung injury on rat model through radiology and histology.

BACKGROUND: Our target was to show the role of high mobility group box-1/receptor for (HMGB1/RAGE) interaction in feces intraperitoneal injection procedure (FIP)-induced acute lung injury (ALI) pathophysiology, to investigate the effect of papaverine on RAGE associated NF-κB pathway by determining the level of soluble RAGE (sRAGE) and HMGB1, and to support this hypothesis by evaluating inflammatory biochemical, oxidative stress markers, Hounsfield unit (HU) value in computed tomography (CT), and histo-pathological results. METHODS: FIP was performed on 37 Wistar rats for creating a sepsis-induced ALI model. The animals were assigned into four groups as follows: Normal control (no treatment), placebo (FIP and saline), and receiving 20 mg/kg and 40 mg/kg per day papaverine. Twenty h after FIP, CT examination was performed for all animals, and HU value of the lung parenchyma was measured. The plasma levels of tumor necrosis factor (TNF)-α, HMGB1, sRAGE, C-reactive protein (CRP) and malondialdehyde (MDA), and lactic acid (LA) were determined and PaO2 and PaCO2 were measured from arterial blood sample. Lung damage was assessed by histopathological. RESULTS: TNF-, IL-6, CRP, HMGB1, MDA, LA levels, histopathologic scores, and HU values of CT were significantly increased and sRAGE levels were decreased in the saline-treated group against normal group (all P<0.05). Papaverine significantly reversed all results regardless of the dose (all P<0.05) and demonstrated inhibition of HMGB1/RAGE interaction through increasing sRAGE levels and suppresses the pro-inflammatory cytokines. CONCLUSION: We concluded that papaverine has ameliorating effects in rat model of ALI.

Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD. METHODS: Twenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively. RESULTS: In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function. CONCLUSION: In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.

Atorvastatin Improves the Propionic Acid-Induced Autism in Rats: The Roles of Sphingosine-1-Phosphate and Anti-inflammatory Action.

Purpose The aim of this study is to investigate the benefits of atorvastatin on the propionic acid-induced autism model via increasing sphingosine-1-phosphate and anti-inflammatory actions with imaging and brain tissue investigations. Materials and methods Twenty-five mg/kg/day/rat of propionic acid (PPA) was administered intraperitoneally to 20 male Wistar rats, and 10 male Wistar rats were fed orally. Study groups were designed as follows: Group 1: Control Group (orally fed control, n=10); Group 2 (PPA+saline, n=10); Group 3 (PPA+Atorvastatin, n=10). The brain biochemical and histopathology assessments and magnetic resonance (MR) imaging were conducted across groups in order to compare them. Results The PPA+Atorvastatin group was found to have significantly lower levels of brain malondialdehyde, IL-2 level, IL-17, tumor necrosis factor-alpha (TNF-α), and lactate compared to the PPA+saline group. The PPA+Atorvastatin group had higher levels of nerve growth factor and nuclear factor erythroid 2-related factor 2 (NRF-2) and sphingosine-1-phosphate. In histopathology assessments, the PPA+Atorvastatin group was found to have significantly higher neuronal counts of CA1 and CA2 in the hippocampus, and Purkinje cells in the cerebellum. Conclusions Current findings suggest that atorvastatin increases sphingosine-1-phosphate levels and decreases inflammatory actions which characterize the autism rodent model implemented in this study. These preliminary results have to be confirmed by further experimental and clinical studies.

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.

N-acetyl cysteine: A new look at its effect on PTZ-induced convulsions.

INTRODUCTION/AIM: Epilepsy is widely investigated as a common neurological disease requiring pharmacologically effective agents. N-acetyl cysteine (NAC), has become a remarkable molecule with its role in both antioxidant and glutaminergic modulation. There are many points and processes waiting to be revealed regarding the role of NAC in epilepsy. MATERIALS AND METHODS: Pentylenetetrazole (PTZ) was administered to induce seizures in a total number of 48 Sprague-Dawley rats. 35 mg/kg PTZ dose as a sub-convulsive dose was administered to 24 animals to monitor EEG changes, while 70 mg/kg PTZ dose which was a convulsive dose was administered to 24 animals to determine seizure-related behavioral changes with the Racine's scale. 30 min before the seizure-induced procedure, NAC was administered at doses of 300 and 600 mg/kg as pretreatment to investigate anti-seizure and anti-oxidative effects. The spike percentage, the stage of convulsion, and the onset time of the first myoclonic jerk were evaluated to determine the anti-seizure effect. Furthermore, its effect on oxidative stress was determined by measuring both malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity. RESULTS: There was a dose-dependent reduction in the seizure stage and prolonged onset time of the first myoclonic jerk in rats with NAC pretreatment. EEG recordings resulted in a dose-dependent decrease in spike percentages. Moreover, the same dose-dependent changes were observed in oxidative stress biomarkers, both 300 mg/kg NAC and 600 mg/kg decreased MDA levels and ameliorated SOD activity. CONCLUSION: We can report that 300 mg/kg and 600 mg/kg doses of NAC are promising with their reducing effect on convulsions and have a beneficial effect by preventing oxidative stress. In addition, NAC has been also determined that this effect is dose-dependent. Detailed and comparative studies are needed on the convulsion-reducing effect of NAC in epilepsy.

Modafinil Improves Autism-like Behavior in Rats by Reducing Neuroinflammation.

To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male Wistar rats were used in the study, divided into 3 groups of ten subjects. One group served as a control, the subjects in the other two were given 250 mg/kg/day of PPA by intraperitoneal injection over the course of 5 days to induce autism. The experimental design was as follows: Group 1: Normal control (orally-fed control, n = 10); Group 2 (PPA + saline, n = 10): PPA and 1 ml/kg/day % 0.9 NaCl saline via oral gavage; Group 3 (PPA + Modafinil, n = 10) PPA and 30 mg/kg/day Modafinil (Modiodal tablets 100 mg, Cephalon) via oral gavage. All of the groups were investigated for behavioral, biochemical, and histological abnormality. Autism-like behaviors were reduced significantly in the rats treated with PPA. TNF-α, Nerve Growth Factor (NGF), IL-17, IL-2, and NF-KB levels as well as MDA levels and lactate were significantly higher in those treated with PPA compared to the control group. Using immunohistochemical methods, the number of neurons and GFAP immunoreactivity was significantly altered in PPA-treated rats compared to the control. Using Magnetic Resonance Spectroscopy (MRS), we found that lactate levels were significantly higher in the PPA-treated rats, while creatinine levels were significantly decreased. In the rats administered with Modafinil, behavior, neuroinflammation, and histopathological changes brought about by PPA were significantly reversed. Our results demonstrate the potential role of Modafinil in ameliorating PPA-induced neuroinflammation in rats.