Influence of Cilostazol on Changes in Cyclin D1 Expression in Cerebral Cortex of Rats with Chronic Cerebral Ischemia.

The influence of cilostazol on learning and memory, and cyclin D1 expression in the cerebral cortex of rats with chronic cerebral ischemia were investigated. A chronic cerebral ischemia model was established using the permanent bilateral common carotid artery occlusion method (2VO), learning and memory capacity was detected using the Morris water maze, and expression changes in apoptosis regulating gene cyclin D1 were tested by RT-PCR. Results of the Morris water maze indicated that significant extensions were found in the escape latent period and swimming path of rats in the ischemia group (2VO group), learning and memory results in the cilostazol group was obviously superior compared to the 2VO group (P<0.05), and the expression of cyclin D1 was observed to increase in both the ischemia and cilostazol intervention groups at the 9th week of ischemia. A significant difference was observed, compared with the sham operation group (P<0.05), the expression level decreased in the ischemia group compared with the cilostazol group, and a significant difference was identified compared with the ischemia group (P<0.05). Cilostazol can reduce nerve function impairment and improve learning and memory functions by affecting changes in apoptosis regulating genes.

Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation.

OBJECTIVE: Nodal is a member of the transforming growth factor ß (TGF-ß) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the  role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury. MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells. RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.

Effects of c-Jun N-terminal kinase on Activin A/Smads signaling in PC12 cell suffered from oxygen-glucose deprivation.

Activin A (Act A), a member of transforming growth factor-ß (TGF-ß) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-ß induced epithelial-mesenchymal transition. However, in neural ischemia, the speculative regulation between JNK and Act A/Smads signaling pathways has not been clarified. To explore this issue, an Oxygen Glucose Deprivation (OGD) model was introduced to nerve-like PC12 cells. We found that JNK signal activation occurred at the early time of OGD injury (1 h). Act A administration suppressed JNK phosphorylation. In addition, JNK inhibition could elevate the strength of Smads signaling and attenuate neural apoptosis after OGD injury. Our results indicated a negative regulation effect of JNK on Smads signaling in ischemic injury. Taken together, JNK, as a critical site for neural apoptosis and negative regulator for Act A/Smads signaling, was presumed to be a molecular therapeutic target for ischemia.

Ultralow-density nanostructured metal foams: combustion synthesis, morphology, and composition.

The synthesis of low-density, nanoporous materials has been an active area of study in chemistry and materials science dating back to the initial synthesis of aerogels. These materials, however, are most often limited to metal oxides, e.g., silica and alumina, and organic aerogels, e.g., resorcinol/formaldehyde, or carbon aerogels, produced from the pyrolysis of organic aerogels. The ability to form monolithic metallic nanocellular porous materials is difficult and sometimes elusive using conventional methodology. Here we report a relatively simple method to access unprecedented ultralow-density, nanostructured, monolithic, transition-metal foams, utilizing self-propagating combustion synthesis of novel transition-metal complexes containing high nitrogen energetic ligands. During the investigation of the decomposition behavior of the high-nitrogen transition metal complexes, it was discovered that nanostructured metal monolithic foams were formed in a post flame-front dynamic assembly having remarkably low densities down to 0.011 g cm(-3) and extremely high surface areas as high as 270 m(2) g(-1). We have produced monolithic nanoporous metal foams via this method of iron, cobalt, copper, and silver metals. We expect to be able to apply this to many other metals and to be able to tailor the resulting structure significantly.