Everolimus, a mammalian target of rapamycin inhibitor, ameliorated streptozotocin-induced learning and memory deficits via neurochemical alterations in male rats

Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. mTOR is a serine/threonine protein kinase and its hyperactivity is involved in the pathophysiology of Alzheimer’s disease (AD) and associated cognitive deficits. The present study evaluated the impact of EVR, on cognitive functions, hippocampal cell loss, and neurochemical parameters in the intracerebroventricular streptozotocin (icv-STZ) model of AD rats. EVR (1 and 5 mg/kg) was administered for 21 days following the single administration of STZ (3 mg/kg, icv) or for 7 days on days 21-28 post-STZ injection after establishment of cognitive dysfunction. Cognitive deficits (passive avoidance and spatial memory), oxidative stress parameters, acetylcholinesterase (AChE) activity, and percentage of cell loss were evaluated in the hippocampus. Chronic administration (1 and 5 mg/kg for 21 days from the day of surgery and icv-STZ infusion) or acute injection (5 mg/kg for 7 days after establishment of cognitive impairment) of EVR significantly attenuated cognitive dysfunction, neuronal loss, oxidative stress and AChE activity in the hippocampus of STZ-AD rats. In conclusion, our study showed that EVR could prevent or improve deteriorations in behavioral, biochemical and histopathological features of the icv-STZ rat model of AD. Therefore, inhibition of the hyperactivated mTOR may be an important therapeutic target for AD

Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats

Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor (S. minor) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI.Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted.Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK (p < 0.001) and elevated MDA levels (p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content (p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase (p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers (p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract.Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress

Corrigendum: Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats

In the published article, there was an error in Figure 4A as published. During the last stage of revision, labels in Figure 4A were inadvertently altered, and the group labels in the figure were mistakenly substituted. The corrected Figure 4A appears below:Scopu

Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals

Neurogenesis, the process of generating functionally integrated neurons from neural stem and progenitor cells, is involved in brain development during embryonic stages but continues throughout life. Adult neurogenesis plays essential roles in many brain functions such as cognition, brain plasticity, and repair. Abnormalities in neurogenesis have been described in many neuropsychiatric and neurological disorders, including epilepsy.While sharing a common property of suppressing seizures, accumulating evidence has shown that some antiseizure medications (ASM) exhibit neuroprotective potential in the non-epileptic models including Parkinson's disease, Alzheimer's disease, cerebral ischemia, or traumatic brain injury. ASM are a heterogeneous group of medications with different mechanisms of actions. Therefore, it remains to be revealed whether neurogenesis is a class effect or related to them all. In this comprehensive literature study, we reviewed the literature data on the influence of ASM on the neurogenesis process during brain development and also in the adult brain under physiological or pathological conditions. Meanwhile, we discussed the underlying mechanisms associated with the neurogenic effects of ASM by linking the reported in vivo and in vitro studies. PubMed, Web of Science, and Google Scholar databases were searched until the end of February 2023. A total of 83 studies were used finally.ASM can modulate neurogenesis through the increase or decrease of proliferation, survival, and differentiation of the quiescent NSC pool. The present article indicated that the neurogenic potential of ASM depends on the administered dose, treatment period, temporal administration of the drug, and normal or disease context

6-Gingerol, an ingredient of Zingiber officinale, abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing oxidative stress and inflammation

Background: Sepsis-induced cardiac dysfunction is the main reason for the high mortality rate in patients with sepsis. For centuries, ginger has been used as a spice and a natural medicinal herb. Gingerols are phenolic compounds extracted from ginger that have promising pharmacological effects. The current research was designed to assess the effect of 6-gingerol on lipopolysaccharide-induced H9c2 cardiomyocyte injury and its underlying mechanisms. Methods: H9c2 cells were pre-incubated for 24 h with a wide range of concentrations of 6-gingerol (5–100 μM). Afterward, 10 μg/ml of LPS was added for another 24 h. Next, the cell viability, the level of reactive oxygen species (ROS) production, lipid peroxidation, and GSH content were measured using MTT, H2DCF-DA, TBA/TCA, and DTNB reagents. In addition, the levels of inflammatory mediators, i.e., interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6, and their gene expression levels were evaluated using ELISA and quantitative real-time PCR. Results: Our study revealed that LPS not only reduced cell viability, but also increased lipid peroxidation, ROS production, and cytokine levels, and decreased GSH levels. The concentration of 25, 50, and 100 μM of 6-gingerol inhibited the LPS-induced H9c2 cellular injury via a decrement in the MDA (25 μM: p< 0.05, 50 and 100 μM: p< 0.001) and ROS production levels (25–100 μM: p< 0.001), while enhancing the GSH content (25–100 μM: p< 0.001). This phytochemical also attenuated the protein levels of TNF-α, IL-β, and IL-6 (all: p< 0.001) and their related genes (all: p< 0.001) at concentrations of 50–100 μM. Conclusion: Pre-treatment with 6-gingerol has potential protective effects on LPS-injured cardiomyocytes by suppressing oxidative stress and inflammation

Prognostic performance of magnetic resonance spectrometry in patients with diffuse axonal injury: A prospective cohort study

Background: Traumatic brain injury (TBI) is a global concern, and many people suffer from TBI annually. Determining the outcome of patients with brain injury has a valuable clinical impact and results in better management of patients. In this study, we aimed to investigate the predictive value of magnetic resonance spectrometry (MRS) in patients with diffuse axonal injury (DAI). Method: This is a prospective cohort study on patients with DAI in 6 months at a tertiary medical center. According to the eligibility criteria, the patients were enrolled in the study. The MRS scan was conducted on days 3 and 30, and the correlation of metabolites of MRS according to the GCS score of patients on days 3 and 30 was investigated to determine the prognostic impact of MRS in patients with DAI. Results: A total of 50 patients with DAI, including 39 males and 11 females, were recruited. MRS of patients on day 3 and 30 was conducted and showed that the level phosphocreatine (r = -0.56, P < 0.001), NAA/choline ratio (r = 0.86, P < 0.001), and hunter angle (r = 0.59, P < 0.001) on day 3 are significantly correlated with the GCS score of patients on day 30. Phosphocreatine (r = -0.84, P < 0.001), phosphocholine (r = -0.86, P < 0.001), NAA/choline (r = 0.89, P < 0.001), myoinositol (r = -0.75, P < 0.001), and hunter angle (r = 0.89, P < 0.001) on day 30 are substantially associated with day 30 GCS score. Conclusion: Among different investigated metabolites, the level of phosphocreatine, NAA/choline ratio, and hunter angle on day three significantly correlated with patients' GCS on day 30