Involvement of Ceramide Metabolism in Cerebral Ischemia

Abstract

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in worldwide. Although reperfusion therapies have shown efficacy in a limited number of patients with acute ischemic stroke, neuroprotective drugs and recovery strategies have been widely assessed, but none of them have been successful in clinical practice. Therefore, the search for new therapeutic approaches is still necessary. Sphingolipids consist of a family of lipidic molecules with both structural and cell signaling functions. Regulation of sphingolipid metabolism is crucial for cell fate and homeostasis in the body. Different works have emphasized the implication of its metabolism in different pathologies, such as diabetes, cancer, neurodegeneration, or atherosclerosis. Other studies have shown its implication in the risk of suffering a stroke and its progression. This review will highlight the implications of sphingolipid metabolism enzymes in acute ischemic stroke.

Determination of endogenous sphingolipid content in stroke rats and HT22 cells subjected to oxygen-glucose deprivation by LC‒MS/MS

“…Mechanical thrombectomy or intravenous thrombolysis is often used alone or in combination, and the combination of thrombectomy and bridging therapy has been reported to restore normal cerebral blood flow [ 4 , 5 ]. Reducing cell death by repairing or establishing alternative neural pathways and synapses to repair nerves or intervene in the ischemic cascade is also meaningful to explore [ 6 ]. The development of neuroprotective drugs for stroke is a slowly evolving process [ 7 ], and it is necessary to explore new targets for stroke treatment.…”

Integrated transcriptomics, proteomics and metabolomics to identify biomarkers of astragaloside IV against cerebral ischemic injury in rats

“…The glycosphingolipid biosynthesisganglioside pathway has been implicated in the pathogenesis of ischemic stroke. 41 Moreover, in many diseases, such as cancer, diabetes, neurodegeneration, and cardiovascular disease, an imbalance in cellular and organismal homeostasis is associated with sphingolipid metabolism. 42,43 The galactosidase-1 (Glb1) gene encodes β-galactosidase, which decomposes the GM1 ganglioside.…”

Need for a Paradigm Shift in the Treatment of Ischemic Stroke: The Blood-Brain Barrier

“…Other molecules with structural and signalling functions called ceramides have been described to be involved in stroke [ 182 ]. In this regard, high levels of long-chain ceramide have been associated with BBB disruption and disfunction [ 183 , 184 ].…”