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.

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.

Assessment of Apparent Diffusion Coefficient Parameters and Coefficient of Variance in Discrimination of Receptor Status and Molecular Subtypes of Breast Cancer.

OBJECTIVE: The objective of this study was to investigate the diagnostic power of apparent diffusion coefficient/coefficient of variance (ADCcV) as well as ADC parameters formed based on magnetic resonance images (MRI) in the distinction of molecular breast cancer subtypes. METHODS: The study involved 205 patients who had breast cancer at stages 1-3. Estrogen receptor (EsR), progesterone receptor (PrR), human epidermal growth factor receptor 2 (Her2), and proliferation index (Ki-67) were histologically analyzed in the tumor. The correlations between the immunohistochemistry and intrinsic subtypes were analyzed using ADC and ADCcV. RESULTS: The maximum whole tumor (WTu) ADC (p=0.004), minimum WTu ADC (p<0.001), and mean WTu ADC (p<0.001) values were significantly smaller in the EsR-positive tumors than those in the EsR-negative tumors. Compared to the PrR-negative tumors, the PrR-positive tumors showed significantly smaller maximum, minimum, and mean WTu ADC values (p=0.005, p=0.001, and p<0.001, respectively). In the comparisons of the molecular subtypes in terms of ADCcV, the p-values indicated statistically significant differences between the luminal A (lumA) group and the triple negative (TN) group, between the luminal B (lumB) group and the TN group, and between the Her2-enriched and TN groups (p<0.001, p=0.011, and p=0.004, respectively). Considering the luminal and non-luminal groups, while a significant difference was observed between the groups considering their minimum, maximum, and mean WTu ADC values, their ADCcV values were similar (p<0.001, p=0.004, and p<0.001, respectively). CONCLUSION: Using ADCcV in addition to ADC parameters increased the diagnostic power of diffusion weighted-MRI (DW-MRI) in the distinction of molecular subtypes of breast cancer.

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.

Vitamins C and E protect from sepsis-induced lung damage in rat and CT correlation.

BACKGROUND: Sepsis is one of the leading causes of death in intensive care units worldwide. Vitamins C and E are natural antioxidants and anti-inflammatory agents. Suppressing the inflammation is an important treatment target because it plays a role in the pathophysiology of sepsis. The purpose of this study was to investigate the effect of vitamins C and E treatment in rats with sepsis-induced lung damage. METHODS: In this animal study, fecal intraperitoneal injection procedure (FIP) was performed on 30 of 40 rats included for creating a sepsis model. Rats were randomly assigned into four groups: Group 1, control group (no procedure was applied, n = 10), Group 2, FIP (untreated septic group n = 10), Group 3, FIP+vitC (treated with 500 mg/kg/day ascorbic acid, n = 10), and Group 4, FIP+vitE (treated with 300 mg/kg/day alpha-tocopherol, n = 10). Chest CT was performed in all rats and density of the lungs was measured by using Hounsfield unit (HU). Histopathological examination of lung damage was performed, and blood samples were collected for biochemical analysis. RESULTS: TNF-α, CRP, IL 1-ß, IL-6, and MDA plasma levels in groups treated with vitamin C or vitamin E were lower than in the FIP group. Histological scores in groups treated either with vitamin C or vitamin E were significantly lower as compared to those in the FIP group. The HU value of lung in groups treated wither with vitamin C or vitamin E were lower than that in the FIP group (p < 0.05). CONCLUSION: The rats treated either with vitamin C or E showed improved results for sepsis. We think that they can be used as adjuvant therapy for septic patients because of their effectivity and low costs (Tab. 3, Fig. 2, Ref. 27).

Demonstration of ameliorating effect of vardenafil through its anti-inflammatory and neuroprotective properties in autism spectrum disorder induced by propionic acid on rat model.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology. In this study, we aimed to determine the ameliorating effects of vardenafil in the ASD rat model induced by propionic acid (PPA) in terms of neurobehavioral changes and also support these effects with histopathological changes, brain biochemical analysis and magnetic resonance spectroscopy (MRS) findings. MATERIALS AND METHODS: Twenty-one male rats were randomly assigned into three groups. Group 1 (control, 7 rats) did not receive treatment. Rats in groups 2 and 3 were given PPA at the dose of 250 mg/kg/day intraperitoneally for 5 days. After PPA administration, animals in group 2 (PPAS, 7 rats) were given saline and animals in group 3 (PPAV, 7 rats) were given vardenafil. Behavioral tests were performed between the 20th and 24th days of the study. The rats were taken for MRS on the 25th day. At the end of the study, brain levels of interleukin-2 (IL-2), IL-17, tumor necrosis factor-α, nerve growth factor, cGMP and lactate levels were measured. In the cerebellum and the CA1 and CA3 regions of the hippocampus, counts of neurons and Purkinje cells and glial fibrillary acidic protein (associated with gliosis) were evaluated histologically. RESULTS: Three chamber sociability and passive avoiding test, histopathological results, lactate levels derived from MRS, and biochemical biomarkers revealed significant differences among the PPAV and PPAS groups. CONCLUSION: We concluded that vardenafil improves memory and social behaviors and prevent loss of neuronal and Purkinje cell through its anti-inflammatory and neuroprotective effect.

Effects of flexible ureteroscopy on renal blood flow: a prospective evaluation.

OBJECTIVE: This study aimed to investigate the effects of flexible ureteroscopy (F-URS) on renal blood flow using renal Doppler ultrasound (US). MATERIALS AND METHOD: Patients undergoing F-URS were scheduled for Doppler US preoperatively and postoperatively. Peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) were reported. Technical details, operation time, stone characteristics and complications were recorded. Patients were grouped as 9.5/11.5-Flex-X2, 10/12-Flex-X2, 10/12-Flex-XC, 12/14-Flex-X2 and 12/14-Flex-XC, with 28, six, three, seven and two patients in each group, respectively. RESULTS: Forty-six patients with a mean age of 41.24 years and stone volume of 1685 mm³ were enrolled. The PSV, EDV, PI and RI of renal arteries in all groups in preoperative and postoperative periods were similar. Arcuate artery measurements in all groups were also similar in preoperative and postoperative periods, without any significant difference except in two parameters: RI in the 9.5/11.5-Flex-X2 group and PSV in the 12/14-Flex-X2 group. The resistive index in the arcuate artery of the 9.5/11.5-Flex-X2 group was increased from 0.59 to 0.62 cm/sec postoperatively. The PSV in the arcuate artery of the 12/14-Flex-X2 group was decreased from 30.9 to 27.2 cm/sec. Three patients had urinary tract infections postoperatively and two had sepsis. CONCLUSION: This study suggests that compatible ureteroscope-ureteral access sheath combinations with a lumen difference of more than 1.5 Fr can provide safe outcomes in terms of renal blood flow. F-URS can safely be performed in terms of renal perfusion and complication rates with appropriate equipment and instruments.