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Sphingolipids in rat model of transient focal cerebral ischemia: implication for stroke injury
Author(s) -
Khan M.,
Sekhon B. K.,
Sekhon C. S.,
Singh I.,
Singh A. K.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.42_10.x
Subject(s) - ceramide , sphingomyelin , ischemia , cardiolipin , lipid signaling , apoptosis , neuroprotection , brain ischemia , sphingolipid , medicine , oxidative stress , stroke (engine) , pharmacology , endocrinology , chemistry , biochemistry , cholesterol , inflammation , membrane , phospholipid , mechanical engineering , engineering
Lipids are essential for signal transduction in response to trauma leading to neurodegeneration. Ceramide is an important mediator of apoptosis and cell proliferation. We studied the involvement of ceramide/sphingomyelin pathway in rat brain (stroke model) after 45 min ischemia followed by 24‐h reperfusion. Ischemia was performed through occlusion of right middle cerebral artery (MCA). The level of ceramide was found increased (70–100% in ischemic side of brain v/s contralateral side of brain). Sphingomyelin levels were also decreased by 20–25% in ischemic brain v/s contralateral side of brain. Increase in ceramide and decrease in sphingomyelin were in good agreement with observed apoptotic cell loss (TUNEL assay) and decrease in the level of cardiolipin (a mitochondrian specific phospholipids) in affected ischemic brain. N‐acetyl cysteine (NAC), a therapeutic agent recognized as potent antioxidant provided protective effect. Pretreatment with NAC before ischemia reduced the infarct volume size, suppressed apoptosis, restored cardiolipin level and decreased the levels of free fatty acids. However, NAC did not normalize the ceramide level. These interesting observations raise a question about the role of ceramide and its relationship with apoptosis and oxidative stress in rat brain ischemia. Acknowledgements: Supported by NIH grants NS‐40144, NS‐40810, NS‐22576, NS‐34741 and NS‐37766.