Benzodiaze pine receptors consist of two types of receptors, cent

Benzodiaze pine receptors consist of two types of receptors, central type benzodiazepine Romidepsin HDAC receptors, which are coupled to type A gamma amminobutyric acid receptors, and peripheral type benzodiazepine receptors, which are not coupled to GABAA receptors. Although it has been demonstrated that midazolam binds to and activates both CBRs and PBRs, midazolam Inhibitors,Modulators,Libraries has a hypnotic effect that is mediated via CBRs in neurons. With regard to receptor expres sion, CBRs are expressed exclusively in the CNS. Expression of CBRs coupled to GABAA receptors in astrocytes has been shown to be influenced by astrocytic maturation, differentiation, and activation. In con trast, PBRs are detected in many peripheral tissues and cells, such as kidney, endocrine organs and monocytes.

While the expression levels of PBRs are low in normal human Inhibitors,Modulators,Libraries brain, levels in both astrocytes and microglia increase in conditions of glial activation, for example, inflammation, brain injury, neurodegenerative states, and gliomas. C6 cells, derived from rat glioma cells, have been shown to express PBRs and few CBRs. These cells are thus suitable for investigations of PBR functions in astrocytes. PBRs have been reported to function in the regulation of cellular Inhibitors,Modulators,Libraries proliferation, immunomodulation, steroido genesis, oxidative processes, and programmed cell death. Several animal studies have demonstrated that midazolam can improve neural recovery after anoxia and ischemia. Cytokines, particularly interleukin 1b and tumor necrosis factor a, activate the immune system and enhance brain damage.

Midazo lam has been Inhibitors,Modulators,Libraries shown to inhibit IL 6 mRNA expression in human peripheral blood mononuclear cells, and to suppress lipopolysachccaride induced nitric oxide and TNF a release from rat microglia via PBRs. Thus, these results led us to speculate Inhibitors,Modulators,Libraries that midazo lam might modulate immune system function in the CNS. However, the exact mechanism of action of mida zolam effects on immune system in the CNS remain to be fully elucidated. In the physiological CNS, IL 1b, a pro inflammatory cytokine, is expressed at low levels. IL 1 plays a role in some physiological processes including sleep and synaptic plasticity. Levels of IL 1b increase in cere brospinal fluid in patients with traumatic brain injury, stroke and neurodegenerative diseases. The main source of brain IL 1b after acute insult is microglia.

Astrocytes also produce IL 1b in response to such stimuli, with a time course slightly later than that of microglia. IL 1b induces the production of other cytokines, such as TNF a and IL 6, from micro glia and astrocytes. We have previously cisplatin mechanism of action reported that IL 1b significantly induces IL 6 synthesis in C6 glioma cells. Cytokines like IL 1b and IL 6 have been implicated in neuroinflammation, astrogliosis, brain ischemia and chronic CNS diseases. In the present study, we investigated the effect of midazo lam on IL 1b induced IL 6 release from C6 cells, and the mechanisms underlying this effect.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>