Characterization of the temporo-spatial effects of chronic bilateral intrahippocampal cannulae on interleukin-1beta

ABSTRACT

The implantation of a foreign object in the brain produces an acute neuroinflammatory state in which glia (astrocytes and microglia) may remain chronically activated in response to the inert foreign object. Activated glia can exhibit a sensitized pro-inflammatory response to immunogenic stimuli. This may be relevant to intracranial cannula implantation, which is commonly used to administer substances directly into the brain. If intracranial cannulation activates glia, a subsequent neuroinflammatory stimulus might induce a potentiated pro-inflammatory response, thereby introducing a potential experimental confound. We tested the temporal and spatial responses of interleukin-1β (IL-1β) to an acute immune challenge produced by lipopolysaccharide (LPS) in animals with chronic bilateral intrahippocampal cannulae implants (stainless steel). Cannulation increased the gene expression of the microglia activation antigens MHC II and CD11b, but not the astrocyte antigen GFAP. Moreover, this activation was temporally and spatially dependent. In addition, IL-1β mRNA, but not IL-1β protein, was significantly elevated in cannulated animals. Administration of LPS, however, significantly potentiated the brain IL-1β response in cannulated animals, but not in stab wounded or naïve animals. This IL-1β response was also temporo-spatially dependent. Thus, the pro-inflammatory sequelae of intracranial cannulation should be considered when designing studies of neuroinflammatory processes(AU)