Radioprotective and Radiomitigative Effects of Melatonin in Tissues with Different Proliferative Activity

We used various markers to analyze damage to mouse tissues (spleen and cerebral cortex) which have different proliferative activity and sensitivity to ionizing radiation (IR). We also assessed the degree of modulation of damages that occurs when melatonin is administered to mice prior to and after their X-ray irradiation. The data from this study showed that lesions in nuclear DNA (nDNA) were repaired more actively in the spleen than in the cerebral cortex of mice irradiated and treated with melatonin (N-acetyl-5-methoxytryptamine). Mitochondrial biogenesis involving mitochondrial DNA (mtDNA) synthesis was activated in both tissues of irradiated mice. A significant proportion of the newly synthesized mtDNA molecules were mutant copies that increase oxidative stress. Melatonin reduced the number of mutant mtDNA copies and the level of H2O2 in both tissues of the irradiated mice. Melatonin promoted the restoration of ATP levels in the tissues of irradiated mice. In the mouse tissues after exposure to X-ray, the level of malondialdehyde (MDA) increased and melatonin was able to reduce it. The MDA concentration was higher in the cerebral cortex tissue than that in the spleen tissue of the mouse. In mouse tissues following irradiation, the glutathione (GSH) level was low. The spleen GSH content was more than twice as low as that in the cerebral cortex. Melatonin helped restore the GSH levels in the mouse tissues. Although the spleen and cerebral cortex tissues of mice differ in the baseline values of the analyzed markers, the radioprotective and radiomitigative potential of melatonin was observed in both tissues.

Effect of astaxanthin on malondialdehyde level in damaged cerebral cortex tissue in male rat (Rattus norvegicus) induced by formaldehyde orally

Background: Malondialdehyde (MDA) is a dialdehyde substance that is the final product of lipids peroxidation in the human body, and it can be used as a biomarker of oxidative stress. One of the most potent antioxidants known nowadays is astaxanthin. This study aims to investigate the effect of astaxanthin on the MDA level in cerebral cortex tissue of Rattus norvegicus, which was given oral formaldehyde.

Identification of Potential Biomarkers and Pathways in Neonatal Hypoxic-Ischemic Brain Injury: Based on Bioinformatics Technology

Background Neonatal hypoxic-ischemic brain damage (HIBD) is one of the most common serious diseases in newborns, with a high mortality and disability rate. This study aims to use the bioinformatics analysis to identify potential hematologic/immune systems tissue-specific genes and related signaling pathways neonatal HIBD.Methods Microarray datasets in HIBD were downloaded from the Gene Expression Omnibus database, and DEGs were identified by R software.Enrichment analyses were performed and protein–protein interaction networks were constructed to understand the functions and enriched pathways of DEGs and to identify central genes and key modules. Results In the cerebral cortex tissue with HIBD, 2598 DEGs were identified, including 2362 up-regulated and 236 down-regulated DEGs. In the blood with HIBD, 1442 DEGs were identified, including 540 up-regulated and 902 down-regulated DEGs. The results of biological processes and KEGG enrichment were very similar in DEGs of the two kinds of tissues, and both involved inflammation, immunity and apoptosis. The common DEGs of the two kinds of tissues also showed similar results in biological processes and KEGG enrichment.and four hematologic/immune system tissues specifically expressed potential biomarker genes were confirmed through a variety of methods, which were verified by GEO datasets and published experimental research. Conclusion The DEGs of HIBD including the potential peripheral biomarkers TYROBP, ITGAM, EGR1 and HMOX1, which may play a role in the pathogenesis of HIBD through inflammation and immune-mediated signaling pathways.

Pregabalin induces pathological changes in cerebrum and cerebellum of Albino Rats

Background: Pregabalin (PGB) used as analgesic in remedy of neurogenic pains of persistent diseases, is taken into consideration as one of the maximum abused anti-epileptic pills and it's been proved that it induces addictive behaviors. The current study investigated the impact of PGB management on cerebral cortex and cerebellar cortex, in each acute and chronic toxicity. Seventy- male and non-pregnant female albino rats’ 6- to 8-week-vintage divided into three principal corporations of 24 rats each had been studied. Group 1 was the control group, group 2 represented the acute toxicity group, and group three represented the hronic toxicity group. Rats had been sacrificed and examined. Result: Cerebral cortex tissue of acute toxicity group displayed astrocytosis and dystrophic changes, while the chronic toxicity group showed degeneration, necrosis and inflammatory cell infiltrates. The cerebellum of chronic toxicity group showed affection of Purkinje cells. Conclusion: Acute and chronic intoxication with pregabalin adversely altered the structure and thus the function of the cerebral cortex and cerebellum.

RKC-B1 Blocks Activation of NF-κB and NLRP3 Signaling Pathways to Suppress Neuroinflammation in LPS-Stimulated Mice

RKC-B1 is a novel fermentation product obtained from the marine micromonospora FIM02-523A. Thus far, there have been few reports about the pharmacological activity of RKC-B1. In our present study, we investigated the anti-neuroinflammatory effects and the possible mechanism of RKC-B1 in LPS-stimulated mice. After treatment with RKC-B1, RNA-seq transcriptome of the cerebral cortex tissue was conducted to find the differentially expressed genes (DEGs). Inflammatory cytokines and proteins were evaluated by ELISA and WB. In RNA-seq analysis, there were 193 genes screened as core genes of RKC-B1 for treatment with neuroinflammation. The significant KEGG enrichment signaling pathways of these core genes were mainly included TNF signaling pathway, IL-17 signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway and others. The corresponding top five KEGG enrichment pathways of three main clusters in PPI network of core genes were closely related to human immune system and immune disease. The results showed that RKC-B1 reduced the levels of pro-inflammatory factors (IL-6, IL-1β, MCP-1, and ICAM-1) and the expression of COX2 in cerebral cortex tissue. Additionally, we found that the anti-neuroinflammation activity of RKC-B1 might be related to suppress activating of NF-κB and NLRP3/cleaved caspase-1 signaling pathways. The current findings suggested that RKC-B1 might be a promising anti-neuroinflammatory agent.

Histopathological Assessment of the Effect of Pregabalin Toxicity on Cerebrum and Cerebellum of Adult Albino Rats

Background: Pregabalin (PGB) used as analgesic in treatment of neurogenic pains of chronic diseases, is considered as one of the most abused anti-epileptic drugs worldwide and it has been proved that it induces addictive behaviors. The present histopathological study aimed to identify the effect of PGB administration on cerebral cortex and cerebellar cortex, in both acute and chronic toxicity. Seventy-two male and non-pregnant female adult albino rats’ 6- to 8-week-old divided into 3 main groups of 24 rats each were studied. Group 1 represented the control group and group 2 represented the acute toxicity group, in which rats were given a single dose of PGB (5000 mg/kg) orally by gavage and after 24 hours, rats were sacrificed and examined. Group 3 represented the chronic toxicity group; were given PGB 500 mg/kg orally by gavage for 12 weeks, after which rats were sacrificed and examined. Result: Cerebral cortex tissue of acute toxicity group displayed astrocytosis and dystrophic changes, while in chronic group showed degeneration, necrosis and cellular infiltrates. The cerebellum of chronic groups showed degeneration and shrunken of Purkinje cells. Conclusion: Acute and chronic intoxication with pregabalin adversely altered the structure of cerebral cortex and cerebellum.

Hypoxia preconditioning protects neuronal cells against traumatic brain injury through stimulation of glucose transport mediated by HIF-1α/GLUTs signaling pathway in rat

Hypoxia preconditioning (HPC), a well-established preconditioning model, has been shown to protect the brain against severe hypoxia or ischemia caused by traumatic brain injury (TBI), but the mechanism has not been well elucidated. Anaerobic glycolysis is the major way for neurons to produce energy under cerebral ischemia and hypoxia after TBI, and it requires large amounts of glucose. We hypothesized that glucose transport, as a rate-limiting step of glucose metabolism, may play key roles in the neuroprotective effects of HPC on cerebral cortex tissue against TBI. The aim of this study was to investigate the effect of HPC on glucose transport activity of rat cerebral cortex tissue after TBI through examining the gene expression of two major glucose transporters (GLUT1 and GLUT3) and their upstream target gene hypoxia-inducible factor-1α (HIF-1α). Sprague-Dawley rats were treated with HPC (50.47 kPa, 3 h/d, 3d). Twenty-four hours after the last treatment, the rats were injured using the Feeney free falling model. Cortex tissues of injured rats were removed at 1 h, 4 h, 8 h, 12 h, 1 day, 3 days, 7 d, and 14 days post-injury for histological analysis. Compared with TBI alone, HPC before TBI resulted in the expression of HIF-1α, GLUT1, and GLUT3 to increase at 1 h; they were markedly increased at 4 h, 8 h, 12 h, 1 day, and 3 days and decreased thereafter (p < 0.05). HPC before TBI could improve neuronal survival in rats by examining NeuN staining and observing reduced apoptosis by examining TUNEL staining. The result showed that HPC before TBI could increase the expression of GLUT1 and GLUT3. And through double immunofluorescence staining for GLUT3 and NeuN, the results strongly suggest that HPC improved glucose transport activity of neurons in rats with TBI. In summary, our results further support that HPC can improve hypoxia tolerance and attenuate neuronal loss of cerebral cortex in rats after TBI. The mechanism is mainly related to the increase of glucose transport activity through inducing GLUT1 and GLUT3 expression through upregulating HIF-1α expression.

Age-linked heterogeneity among oligodendrocyte precursor cells in the cerebral cortex of mice and human

ABSTRACTOligodendrocyte precursor cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present in large parts of the mouse and human central nervous system, both during development and in adulthood, yet how their physiological behaviour is modified throughout life remains largely unknown. Moreover, the activity of adult human OPCs is still not fully understood. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In this article, we have systematically analyzed the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. We also analyze the response of these cells to two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS): FGF2 and anosmin-1. By analyzing intact OPCs for the first time with H-1 HR-MAS NMR spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function of their stage of maturity. Moreover, their response to FGF-2 and anosmin-1 differs in relation to their developmental stage and in function of the species. Our data reveal that the behaviour of adult human and mouse OPCs differs in a very dynamic way that should be considered when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS.