Neurotoxicity research
-
Neurotoxicity research · Aug 2020
Activation of the Melanocortin-4 Receptor Prevents Oxidative Damage and Mitochondrial Dysfunction in Cultured Hippocampal Neurons Exposed to Ethanol.
Excessive alcohol intake affects hippocampal function and neuronal communication through oxidative stress and mitochondrial impairment. Previous studies have suggested that the melanocortin system (MCS) plays an essential role in alcohol consumption and addiction. The MCS is a hypothalamic region involved in regulating inflammatory processes in the brain, and its pharmacological activation through the melanocortin-4 receptor (MC4R) reduces both alcohol consumption and the neuroinflammatory responses in the brain. ⋯ More importantly, RO27-3225 promoted the activation of the antioxidant pathway Nrf-2, demonstrated by an increase in the expression and nuclear translocation of Nrf-2, and upregulation of mRNA levels of NAD(P)H quinone oxidoreductase 1 (NQO1), an antioxidant enzyme which expression is activated by this pathway. These results suggest that the stimulation of MC4R prevents oxidative damage and mitochondrial stress induced by ethanol through the activation of the Nrf-2 pathway in cultured hippocampal neurons. These results are novel and demonstrate the critical function of MC4R in promoting antioxidant defense and reducing mitochondrial damage produced by ethanol in the brain.
-
Neurotoxicity research · Aug 2020
Neonatal Exposure to Anesthesia Leads to Cognitive Deficits in Old Age: Prevention with Intranasal Administration of Insulin in Mice.
Recent pre-clinical and clinical studies suggest that general anesthesia in infants and children may increase the risk of learning disabilities. Currently, there is no treatment for preventing anesthesia-induced neurotoxicity and potential long-term functional impairment. Animal studies have shown that neonatal exposure to anesthesia can induce acute neurotoxicity and long-term behavioral changes that can be detected a few months later. ⋯ Importantly, we found that treatment with intranasal insulin prior to anesthesia exposure can prevent mice from anesthesia-induced cognitive impairment. These results suggest that neonatal exposure to general anesthesia could increase the risk for cognitive impairment during aging. This study also supports pre-treatment with intranasal administration of insulin to be a simple, effective approach to prevent infants and children from the increased risk for age-related cognitive impairment induced by neonatal exposure to general anesthesia.
-
Neurotoxicity research · Jun 2020
Behavioral, Electrophysiological, and Histological Characterization of a New Rat Model for Neoadjuvant Chemotherapy-Induced Neuropathic Pain: Therapeutic Potential of Duloxetine and Allopregnanolone Concomitant Treatment.
Neoadjuvant chemotherapy is beneficial against breast cancer, but its toxicity causes painful chemotherapy-induced neuropathy which decreases seriously patients' quality of life. Development of effective therapy is crucial because current treatments are unsatisfactory. While animal models have previously been produced to test therapeutics against chemotherapy-induced neuropathy, neuropathic pain evoked by the frequently used neoadjuvant-chemotherapy involving sequentially epirubicin and docetaxel has never been modeled. ⋯ This concomitant therapy was more effective than separate duloxetine or allopregnanolone treatment to prevent epirubicin-docetaxel induced cold allodynia, mechanical allodynia/hyperalgesia, peripheral nerve functional/electrophysiological, and histological alterations. Interestingly, duloxetine-allopregnanolone concomitant treatment (but not duloxetine) also prevented epirubicin-docetaxel induced Schwann cell dedifferentiation and related macrophage (CD11b/c-positive cells) infiltration in sciatic nerves. Altogether, our results suggest that duloxetine and allopregnanolone concomitant treatment may represent a promising therapeutic option to counteract efficiently painful neuropathy or epirubicin-docetaxel evoked peripheral nerve tissue damages and dysfunctions.
-
As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. ⋯ Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.
-
Neurotoxicity research · Feb 2020
Observational StudyThe Association Between Serum Macrophage Migration Inhibitory Factor and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.
Inflammatory processes have long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Macrophage migration inhibitory factor (MIF) has been implicated in inflammation. The aim of this study was to assess whether serum levels of MIF at admission helps to predict which patients with aSAH would subsequently develop DCI. ⋯ Interestingly, the combined model (MIF/IL-6/CRP) improved the MIF to predict DCI (AUC of the combined model: 0.811; 95% CI, 0.751-0.871; P = 0.024). Furthermore, inclusion of MIF in the existing risk factors for the prediction of DCI enhanced the index and net reclassification improvement (NRI) (P < 0.001) and integrated discrimination improvement (IDI) (P = 0.005) values, confirming the effective reclassification and discrimination. The data showed that elevated MIF serum level accurately identifies patients at highest risk for developing DCI following aSAH.