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Ischemic stroke (IS), a devastating condition characterized by intracranial artery stenosis and middle cerebral artery occlusion leading to insufficient oxygen supply to the brain, is a major cause of death and physical disability worldwide. Recent research has demonstrated the critical role of circular RNAs (circRNAs), a class of covalently enclosed noncoding RNAs that are widespread in eukaryotic cells, in regulating various physiological and pathophysiological cellular processes, including cell apoptosis, autophagy, synaptic plasticity, and neuroinflammation. In the past few years, circRNAs have attracted extensive attention in the field of IS research. This review summarizes the current understanding of the mechanisms underlying the involvement of circRNAs in IS development. A better understanding of circRNA-mediated pathogenic mechanisms in IS may pave the way for translating circRNA research into clinical practice, ultimately improving the clinical outcomes of IS patients. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of long-lasting disability in human and oxidative stress an important underlying cause. Molecular insights into pathophysiology of ischemic stroke are still obscure, and the present study investigated the protective effect of high dosage Grape Seed Extract (GSE 2.5 g/kg) on brain ischemia-reperfusion (I/R) injury using a proteomic approach. Ischemia was realized by occlusion of the common carotid arteries for 30 min followed by 1 h reperfusion on control or GSE pre-treated rats, and a label-free quantification followed by mass spectrometry analysis used to evaluate I/R induced alterations in protein abundance and metabolic pathways as well as the protection afforded by GSE. I/R-induced whole brain ionogram dyshomeostasis, ultrastructural alterations, as well as inflammation into hippocampal dentate gyrus area, which were evaluated using ICP-OES, transmission electron microscopy and immuno-histochemistry respectively. I/R altered the whole brain proteome abundance among which 108 proteins were significantly modified (35 up and 73 down-regulated proteins). Eighty-four proteins were protected upon GSE treatment among which 27 were up and 57 down-regulated proteins, suggesting a potent protective effect of GSE close to 78%of the disturbed proteome. Furthermore, GSE efficiently prevented the brain from I/R-induced ion dyshomeostasis, ultrastructural alterations, inflammatory biomarkers as CD56 or CD68 and calcium burst within the hippocampus. To conclude, a potent protective effect of GSE on brain ischemia is evidenced and clinical trials using high dosage GSE should be envisaged on people at high risk for stroke. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic brain injury (HIBI) in neonates is one of the major contributors of newborn death and cognitive impairment. Numerous animal studies have demonstrated that autophagy is substantially increased in HIBI and that sevoflurane postconditioning (SPC) can attenuate HIBI. However, if SPC-induced neuroprotection inhibits autophagy in HIBI remains unknown. To investigate if cerebral protection induced by SPC is related to decreased autophagy in the setting of HIBI. Postnatal rats at day 7 (P7) were randomly assigned to 7 different groups: Sham, HIBI, SPC-HIBI, HIBI + rapamycin, SPC-HIBI + rapamycin, HIBI + p-extracellular signal-regulated kinase (p-ERK) inhibitor, and SPC-HIBI + p-ERK inhibitor. To induce HIBI, neonatal rats underwent left common carotid artery ligation, followed by 2 h of hypoxia (8% O2). Rats in the SPC groups were treated with 1 minimum alveolar concentration ([MAC], 2.4%) SPC for 30 min after HIBI induction. Markers of autophagy and expression of ERK cascade components were measured in the rat brains after 24 h. Spatial learning and memory function were examined 29-34 days after administration of an autophagy agonist or a p-ERK inhibitor. The expression of microtubule-associated proteins 1A/1B, light chain 3B II (LC3-II) and tuberous sclerosis complex 2 (TSC2) were decreased in the SPC-HIBI group compared to the HIBI group. Expression of the p62 sequestosome 1 (P62/SQSTM1) protein, p-ERK/ERK, phospho-mammalian target of rapamycin (p-mTOR) and phospho-p70S6 were increased in SPC-HIBI group. Rats within the SPC-HIBI groups that also received the p-ERK inhibitor or autophagy inhibitor demonstrated reduced cross platform times and increased escape latency. Approximately 30 min of 2.4% SPC treatment in the P7 rat HIBI model attenuated excessive autophagy in the brain by elevating the ERK cascade. This finding provides additional insight into HIBI and identifies new targets for therapeutic approaches to treat HIBI. [ABSTRACT FROM AUTHOR]

The profound significance of autophagy as a cell survival mechanism under conditions of metabolic stress is a well-proven fact. Nearly a decade-long research in this area has led scientists to unearth various roles played by autophagy other than just being an auto cell death mechanism. It is implicated as a vital cell survival pathway for clearance of all the aberrant cellular materials in case of cellular injury, metastasis, disease states, cellular stress, neurodegeneration and so on. In this review, we emphasise the critical role of autophagy in the environmental stressors-induced neurotoxicity and its therapeutic implications for the same. We also attempt to shed some light on the possible protective role of autophagy in developmental neurotoxicity (DNT) which is a rapidly growing health issue of the human population at large and hence a point of rising concern amongst researchers. The intimate association between DNT and neurodegenerative disorders strongly indicates towards adopting autophagy activation as a much-needed remedy for DNT. [ABSTRACT FROM AUTHOR]

Decades of research have revealed numerous differences in brain structure size, connectivity and metabolism between males and females. Sex differences in neurobehavioral and cognitive function after various forms of central nervous system (CNS) injury are observed in clinical practice and animal research studies. Sources of sex differences include early life exposure to gonadal hormones, chromosome compliment and adult hormonal modulation. It is becoming increasingly apparent that mitochondrial metabolism and cell death signaling are also sexually dimorphic. Mitochondrial metabolic dysfunction is a common feature of CNS injury. Evidence suggests males predominantly utilize proteins while females predominantly use lipids as a fuel source within mitochondria and that these differences may significantly affect cellular survival following injury. These fundamental biochemical differences have a profound impact on energy production and many cellular processes in health and disease. This review will focus on the accumulated evidence revealing sex differences in mitochondrial function and cellular signaling pathways in the context of CNS injury mechanisms and the potential implications for neuroprotective therapy development. [ABSTRACT FROM AUTHOR]

Brain and spinal cord injuries initiate widespread temporal and spatial neurodegeneration, through both necrotic and programmed cell death mechanisms. Inflammation, reactive oxidation, excitotoxicity and cell-specific dysregulation of metabolic processes are instigated by traumatic insult and are main contributors to this cumulative damage. Successful treatments rely on prevention or reduction of the magnitude of disruption, and interfering with injurious cellular responses through modulation of signaling cascades is an effective approach. Two intracellular signaling pathways, the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K) and mitogenactivated protein kinase (MAPK) signaling cascades play various cellular roles under normal and pathological conditions. Activation of both pathways can influence anatomical and functional outcomes in multiple CNS disorders. However, some mechanisms involve inhibiting or enhancing one pathway or the other, or both, in propagating specific downstream effects. Though many intracellular mechanisms contribute to cell responses to insult, this review examines the evidence exploring PTEN/PI3K and MAPK signaling influence on pathology, neuroprotection, and repair and how these pathways may be targeted for advancing knowledge and improving neurological outcome after injury to the brain and spinal cord. [ABSTRACT FROM AUTHOR]