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.

Cerebral ischemic postconditioning (IPO) refers to a series of rapid intermittent interruptions of blood flow in the early phase of reperfusion. It protects brain tissue against ischemia-reperfusion injury. IPO decreases infarct volume and neuron loss by activating protein kinases,blocking apoptosis pathways,inhibiting inflammation and oxidative stress. IPO can be applied after cerebral ischemia,and it has better application prospects in clinical practice. This article reviews IPO and its neuroprotective mechanisms.

The interaction between genetic and environmental factors influences the onset,development and prognosis of cerebral ischemia.Recently,epigenetic regulation is increasingly becoming a research focus on cerebral ischemia,and there has been great progress in research on DNA methylation,histone modification and miRNA network.Epigenetic regulation provides a new idea for identifying potential therapeutic targets of cerebral ischemia.

ObjectiveTo investigate the expression change of cathepsin B (CathB) in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after cortical infarction in rats.MethodsThe adult male Sprague-Dawley rats were randomly divided into either a sham operation group or a model group.The latter was further divided into postoperative 1-, 2-, 3-, 4-, and 8-week groups.A model of cerebral cortical infarction was induced by electrocoagulation the cortical branch of middle cerebral artery.Immunohistochemical staining and immunofluorescence were used to detect the protein expression and cellular localization of CathB in the VPN at each time point.ResultsThe expression level of VPN CathB in thalamus increased gradually after cerebral cortical infarction.It reached the peak at 4 weeks, and decreased at 8 weeks, however it was still higher than the control group (all P<0.05).The release of CathB from the lysosomes into the cytoplasm were found.In addition, the expression level of CathB in the activated astrocytes was significantly increased at 3 weeks after cerebral cortical infarction.ConclusionsDuring 1-8 week after cerebral cortex infarction, CathB in the VPN of the ipsilateral thalamus maintained higher expression level, suggesting that it might play a certain role in secondary degeneration in the thalamus after cerebral cortical infarction.

p75 neurotrophin receptor (p75 NTR) is a member of the tumor necrosis factor receptor superfamily, which interacts with tropomyosin receptor kinase (Trk) receptor or binds neurotrophic factors. It mediates a variety of complex signal transduction pathways, induces synaptic growth and affects cell survival. After acute cerebral ischemia, p75 NTR binds effector factors such as pro-nerve growth factor (proNGF) and sortilin, activating downstream apoptotic signal molecules and leading to neuronal death. Therefore, elucidating the pathways and molecular mechanisms of p75 NTR that mediate neuronal apoptosis in acute cerebral ischemia is of great significance for the development of new therapeutic drugs for acute cerebral ischemia.

Exosomes are extracellular small molecular vesicles with lipid bilayers, which contain biologically active substances such as RNA and proteins. Exosomes can conduct material transport and information transmission between cells. After cerebral ischemia, neuron-derived exosomes affect the occurrence and development of neuroinflammation by regulating the activation of glial cells, and the activated glial cells secrete exosomes containing inflammatory factors or inflammation related microRNAs to regulate the survival or death of neurons. Studies have shown that exosomes can be used as biomarkers and therapeutic targets for inflammatory injury after cerebral ischemia. This article describes the composition and function of exosomes, as well as their role and possible mechanism in neuroinflammation after cerebral ischemia.

Objective To investigate the relationship between inflammation and blood coagulation function in the patients with acute exacerbation of chronic cor pulmonale (AECCP) and discuss the potential mechanism and influence on the patients. Methods The present study was based on 30 healthy controls and 141 cases of AECCP in our hospital from January 2011 to June 2014.Levels of white blood cell (WBC), neutrophil (NEUT), high-sensitivity C-reactive protein (hs-CRP, Complement 3 (C3), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and thrombin time (TT) in the patients were determined. Results Compared with the healthy controls, the patients had higher levels of WBC, NEUT, hs-CRP, PT, APTT, FIB, TT (all P < 0.001) and lower level of C3 (P < 0.001). Significant positive correlations were found between the levels of WBC, NEUT and FIB (r = 0.196 and r = 0.199, both P < 0.05); hs-CRP and APTT, FIB(r = 0.234, P < 0.01 and r = 0.466, P < 0.001); C3 and FIB(r = 0.466, P < 0.001), and significant negative correlations were observed between the levels of C3 and PT, APTT, TT (r=-0.258, P<0.01;r=-0.279, P < 0.01 and r = -0.168, P < 0.05, respectively). Compared with the survival patients, the cases of death had higher levels of WBC and NEUT (both P < 0.01). The area under receiver operating characteristic curve of WBC and NEUT, predicting the prognosis, was 0.666 (95% CI 0.552, 0.780; P < 0.01) and 0.695 (95% CI 0.558, 0.801; P = 0.001) respectively. Conclusions Inflammation and blood coagulation function disorder usually coexist in the patients with AECCP, and are closely associated with the severity. Levels of both WBC and NEUT can be used as prognosis predictors for the patients.

Ischemic stroke is a common neurological disorder that can lead to neuronal death and neurological dysfunction. Microglia is the main immune cells in the central nervous system, involved in post-stroke inflammation and tissue repair. Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor expressed on the surface of microglia, plays a multifaceted role in neuronal survival and nerve repair after ischemic stroke, including promoting the phagocytosis of microglia, inhibiting excessive inflammatory response, maintaining the proliferation and survival of microglia, protecting neurons from damage, and promoting the recovery of nerve function. Therefore, elucidating the immunoregulatory mechanism of TREM2 on microglia after cerebral ischemia is of great significance for exploring new therapeutic directions for ischemic stroke.

Phagoptosis is a kind of cell death mode which has been widely concerned in recent years. Previous studies have shown that the phagocytosis of viable neurons by microglia (phagoptosis) may be involved in the pathophysiological processes of various neurological diseases, including ischemic stroke. After cerebral ischemia, microglia chemotaxis towards ischemic brain tissue, and then recognize and engulf the stressed neurons, leading to further damage or even death of neurons, thereby exacerbating cerebral ischemic injury. This article reviews the relationship between phagoptosis and cerebral ischemia, with a focus on elucidating the molecular mechanisms of phagoptosis after cerebral ischemia, in order to provide new targets and strategies for the treatment of cerebral ischemia.

Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase with a kinase domain, which plays an important role in the regulation of necroptosis. After cerebral ischemia, MLKL, as the substrate protein of the receptor-interacting protein 3, undergoes oligomerization and phosphorylation, and then translocates from the cytoplasm to the plasmalemma, causing mitochondrial division and cell membrane rupture. MLKL can also mediate the inflammatory response after cerebral ischemia by inducing necroptosis and directly activating inflammasomes, thereby aggravating brain injury. Therefore, to clarify the biological characteristics of MLKL and its role and mechanism in cerebral ischemia is very important for the treatment of cerebral ischemia.