p38 mitogen-activated protein kinase (MAPK) is an important intracellular signaling transduction pathway.Its major role is involved in inflammatory regulation and apoptosis.p38 MAPK is activated during the cerebral ischemia.Its expression level and the upstream and downstream protein phosphorylation levels will change.Ischemic preconditioning may mediate the survival or death of neuronal cells after cerebral ischemia through signaling transduction pathway.

After being activated by the growth factor-mediated receptor tyrosine kinase phosphorylation, Akt activates a series of substrate molecules, including Forkhead transcription factors etc, which regulate cell survival and death. With the changes of Akt phosphorylation levels (Ser473) after cerebral ischemia, its upstream and downstream protein phosphorylation levels have also changed. Preconditioning may produce ischemic tolerance by changing the levels of Akt protein phosphoryiation. Dysfunction of Akt/PKB signal transduction pathway may mediated neuronal death after cerebral ischemia.

Protein kinase B (PKB), a serine/threonine kinase Akt, regulates many vital cellular functions, such as cell apoptosis, cell cycle progression and glucose metabolism, etc. Akt/PKB carries out these functions mainly through phosphorylation of a number of cellular substrates. As one of the important substrates of Akt, FOXO transcription factors have attracted more and more attention in regulating cell cycle and apoptosis. FOXO transcription factors are primarily regulated by the phosphatidylinositol 3-kinase/Akt signal pathway via phosphorylation,and re-positioning accompanied by sub-cellular distribution. This article reviews the role of FOXO transcri ption factors in neuronal apoptosis after cerebral ischemia.

The basic functions of the Na+/K+ -ATPase is to maintain the balance of the Na+/K+ electrochemical gradient. The latter is indispensable for maintaining cell osmotic pressure,regulating cell volume,and maintaining excitable membrane resting potential. The maintenance of the Na+/K+ -ATPase activity plays the important roles in neurotransmitter uptake in neurons and Ca2+ effiux. The decreased Na+/K+ -ATPase activity and dysfunction participate in the process of ischemic brain injury after cerebral ischemia. Ischemic precondi-tioning induces ischemic tolerance by maintaining the Na+/K+ -ATPase activity after ischemia.Cardiotonic steroids and citicoline may play a neuroprotective effect on cerebral ischemia by improving the Na +/K+ -ATPase activity.

β-Catenin is an adhesion molecule that mediates intercellular adhesion.It can be activated by the classical Wnt signaling pathway and promote cell survival.During cerebral ischemia,the stability of β-catenin decreases and the phosphorylated β-catenin level increases.Up-regulation of β-catenin can inhibit the schemia-induced neuronal apoptosis,promote neurogenesis,maintain the stability of blood-brain-barrier,and protect against cerebral injury.

Glutamate is an essential excitatory neurotransmitter which regulates brain functions.An increase in extracellular glutamate could excessively activate ionotropic glutamate receptors,initiate calcium overload,and lead to cell death after cerebral ischemia.Glutamate transporter-1 (GLT-1) is one of the major glutamate transporters expressed predominantly in astrocytes.Astrocytes also express the enzyme glutamine synthetase (GS) which converts the glutamate to glutamine; the latter is then 'recycled' into neurons.Pretreatment with ceftriaxone (CEF),ischemia and intermittent hypobaric hypoxia could lead to neuroprotection by increasing the expression of GLT-1 and regulating the activity of glutamate transporter in brain.

Autophagy is a degradation process of intracellular composition.It can be divided into four different stages,including initiation,elongation,maturation and autophagosome breakdown.Its role is associated with the degree of cell damage.Moderate activation of autophagy in the case of starvation and hypoxia can promote cell survival; whereas excessive activation during cerebral ischemia can cause cell lysis and promote cell death.Preconditioning may produce ischemic tolerance by appropriate activation of autophagy.Autophagy is strictly regulated by a variety of protein kinases,apoptotic molecules and oxidative stress pathways.

Hypoxia-induciole factor-1 (HIF-1) is an important transcription factor.It participates in the body's response to the hypoxic environment mainly through its active subunit HIF-1α.During cerebral ischemia and hypoxia,the expression of HIF-1α is upregulated and may activate the expressions of multiple downstream target genes involving glycolysis,vascular growth,cell survival and apoptosis.It has an important significance for the improvement of energy metabolism and the establishment of microcirculation after cerebral ischemia.HIF-1α can not only promote the neuronal survival,but also mediate delayed neuronal death.A variety of preconditioning and postconditioning methods may regulate the survival and death of neuronal cells by activating HIF-1α.

Glycogen synthase kinase 3β (GSK3β) is a serine/threonine kinase.Several signaling pathways,such as growth factors and Wnts,inhibit the GSK3β activity,thereby it promotes cell survival At the time of cerebral ischemia,with the changes of the phosphorylated GSK3β level,its upstream and downstream phosphorylation levels also change.Ischemic preconditioning and postconditioning may induce cerebral ischemic tolerance by regulating the GSK3β signaling pathway.

Animals ; Apoptosis ; Bone Neoplasms ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Cell Proliferation ; Chondrosarcoma ; metabolism ; pathology ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Ovarian Neoplasms ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; SOX9 Transcription Factor ; biosynthesis ; genetics ; physiology