Comb Chem High Throughput Screen
May 2024
Background: Ischemic stroke comprises 75% of all strokes and it is associated with a great frailty and casualty rate. Certain data suggest multiple long non-coding Ribonucleic Acids (lncRNAs) assist the transcriptional, post-transcriptional, and epigenetic regulation of genes expressed in the CNS (Central Nervous System). However, these studies generally focus on differences in the expression patterns of lncRNAs and Messenger Ribonucleic Acids (mRNAs) in tissue samples before and after cerebral ischemic injury, ignoring the effects of age.
View Article and Find Full Text PDFMicroglial hyperactivation mediated by sphingosine kinase 1/sphingosine-1-phosphate (SphK1/S1P) signalling and the consequent inflammatory mediator production serve as the key drivers of cerebral ischaemia-reperfusion injury (CIRI). Although SphK1 reportedly controls autophagy and microglial activation, it remains uncertain as to whether SphK1 is similarly capable of regulating damage mediated by CIRI-activated microglia. In the current study, we adopted both in vitro oxygen-glucose deprivation reperfusion (OGDR) models and in vivo rat models of focal CIRI to ascertain this possibility.
View Article and Find Full Text PDFAims: Sphingosine kinase 1 (Sphk1) and the signaling molecule sphingosine-1-phosphate (S1P) are known to be key regulators of a variety of important biological processes, such as neovascularization. Nitric oxide (NO) is also known to play a role in vasoactive properties, whether Sphk1/S1P signaling is able to alter angiogenesis in the context of cerebral ischemia-reperfusion injury (IRI), and whether such activity is linked with NO production, however, remains uncertain.
Methods: We used immunofluorescence to detect the expression of Sphk1 and NOS in cerebral epithelial cells (EC) after IR or oxygen-glucose deprivation (OGDR).
We aimed to assess the neuroprotective mechanism of monosialotetrahexosy-1 ganglioside (GM1) on focal cerebral ischemia/reperfusion (I/R) injury in rats with diabetes. A total of 54 male Wistar rats were induced with diabetes mellitus by administration of streptozotocin (STZ). The rats were then randomized into three groups, including sham group (n=18), I/R group (n=18), and GM1 group (n=18).
View Article and Find Full Text PDFSphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine1-phosphate (S1P), plays an important role in mediating post-stroke neuroinflammation. However, the pathway and mechanism of the Sphk1-mediated inflammatory response remains unknown. In this study, we found that suppression of Sphk1 decreased IL17 production and relieved neuronal damage induced by microglia in cerebral ischemia reperfusion (IR) or in an in vitro oxygen-glucose deprivation reperfusion (OGDR) system.
View Article and Find Full Text PDFA water-soluble polysaccharide, LJPB2, was purified from Lonicera japonica flowers. The present study was aimed to illustrate its structural features and its neuroprotective effect via anti-oxidant activity on focal ischemia/reperfusion (I/R) injury in rat brain. Via chemical and spectral methods, LJPB2, a polysaccharide with molecular weight of 8.
View Article and Find Full Text PDFBackground: Microglial activation is one of the causative factors of neuroinflammation in cerebral ischemia/reperfusion (IR). Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in the regulation of proinflammatory cytokines in activated microglia. Recent research demonstrated that S1P increased IL-17A-secretion and then worsened CNS (central nervous system) inflammation.
View Article and Find Full Text PDFIschemic neuron death is presumably caused by excitotoxicity. Here, we studied whether ischemia impaired astrocytes and GABAergic neurons to exacerbate glutamate-dependent neural excitotoxicity by electrophysiologically recording these nerve cells in cortical slices. Our results showed that ischemia impaired the activity of glutamate-transporters (Glu-T) on the astrocytes, as well as the ability of firing spikes and the response to excitatory synaptic inputs on GABAergic neurons.
View Article and Find Full Text PDFIschemic brain cell death is presumably caused by excitotoxicity. In addition to an increase of glutamate release during ischemia, the deficiency of astrocytic glutamate-reuptake may cause glutamate accumulation, which results in GABAergic neurons being vulnerable to ischemia. To confirm this hypothesis, we studied the pathophysiological changes of cortical astrocytes and GABAergic neurons during ischemia as well as the prevention of their injuries.
View Article and Find Full Text PDFCerebral ischemic stroke is a prevalent disease in senior individuals. The anticoagulation and thrombolysis to recover blood supply as well as the diminution of neural excitotoxicity to protect brain cells have not shown to fully improve stroke patients. The comprehensive mechanisms and medication specificity remain to be addressed.
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