Microglia are a prominent source of inflammatory mediators, these cells undergo profound activation in response to injury. sellckchem They constantly survey the microenvironment for noxious agents and injurious processes, respond to extracellular signals, clean cellular debris and toxic substances, and secret trophic factors, thereby providing neuroprotection after central nervous system injury. On the other hand, activation of microglia, with resultant production of proinflammatory mediators and neurotoxic mole cules, is involved in the spread of secondary injury. There is mounting evidence that microglia activation is one of the major causes of secondary damage after SCI, and that suppressing it can reduce tissue damage and improve morphological functional recovery.

Modulating the microglial inflammatory process might create a niche environment for tissue repair. Recently, a well documented receptor, epidermal Inhibitors,Modulators,Libraries growth factor re ceptor, attracted much attention for its potency in regulating cell activation. Binding of ligands like EGF and tumor necrosis factor, the tyrosine specific protein kinase intrinsic Inhibitors,Modulators,Libraries to EGFR, results in activation, and is followed by transactivation of mitogen activated protein kinase and other downstream signal pathways. The activation of MAPK has been reported to be essential for production of several inflam matory cytokines, such as interleukin Inhibitors,Modulators,Libraries 1B, TNF and IL 6. In the CNS, EGFR localizes in neurons, astrocytes, and oligodendrocytes, as well as in microglia. Activation of EGFR was reported to cause for mation of cribriform structures in astrocytes, related Inhibitors,Modulators,Libraries to guided migration.

EGFR mediates the EGF induced chemotactic and chemokinetic migration of microglia, and EGFR signaling functions in several CNS disor ders, such as ischemia, tuberous sclerosis, and Alzheimers disease, as well as after SCI. Therefore, we hypothesized that regulation of EGFR Inhibitors,Modulators,Libraries signaling may influence activation of microglia and associated neuroinflammation, thus attenuating second ary damage after SCI. In the present study, lipopolysac charide activated microglia cultures and traumatic SCI rats were used as model systems to ob serve phosphorylated EGFR expression, micro glia activation, cytokine production, morphological and functional outcomes, as well as the underlying mechan isms resulting after EGFR blockade by C225 and AG1478, a blocking antibody and a specific tyrosine kinase inhibitor, respectively.

Methods Detailed information of reagents has been provided in Additional file 1. Surgical procedures and reagent delivery All experimental procedures were performed full report in accord ance with protocols approved by the Governmental Ani mal Care Committee of Tongji Medical College. During surgery, rats were placed on a warming pad to maintain body temperature of 37. 0 0. 5 C.