Abstract
IntroductionSystemic inflammation has been shown to significantly worsen the outcome of neurological disease. However, after acute injuries to the brain both pre- and post-conditioning with bacterial endotoxin has been shown to reduce leukocyte recruitment to the CNS. Here, we sought to determine whether viral pre-challenge would have an effect on the outcome of acute CNS inflammation that was distinct from endotoxin.MethodsAnimals received a single intracranial microinjection of IL-1β in the presence or absence of a viral pre-challenge 24 hours prior to surgery. Liver and brain tissue were analysed for chemokine expression by qRT-PCR and leukocyte and monocyte infiltration 12 hours, 3 days and 7 days after the IL-1β injection.ResultsHere, a single injection of adenovirus prior to IL-1β injection resulted in adhesion molecule expression, chemokine expression and the recruitment of neutrophils to the injured CNS in significantly higher numbers than in IL-1β injected animals. The distribution and persistence of leukocytes within the CNS was also greater after pre-challenge, with neutrophils being found in both the ipsilateral and contralateral hemispheres. Thus, despite the absence of virus within the CNS, the presence of virus within the periphery was sufficient to exacerbate CNS disease.ConclusionsThese data suggest that the effect of a peripheral inflammatory challenge on the outcome of CNS injury or disease is not generic and will be highly dependent on the nature of the pathogen.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0178-3) contains supplementary material, which is available to authorized users.
Highlights
Systemic inflammation has been shown to significantly worsen the outcome of neurological disease
Chemokine expression in the central nervous system (CNS) is selectively affected by viral pre-challenge In keeping with previous observations, the microinjection of IL-1β into the brain caused an up-regulation of cytokines and chemokines known to be involved in leukocyte migration and recruitment (CXCL-1, IL-1β, and C-C chemokine ligand (CCL)-3) at 12 hours post-injection (Additional file 2: Figure S1)
While cytokine and chemokine expression profiles were examined at all time points, significant differences in expression were found between vehicle/IL-1β and AdLuc/IL-1β at 3 days post-injection (Figure 1)
Summary
Systemic inflammation has been shown to significantly worsen the outcome of neurological disease. After acute injuries to the brain both pre- and post-conditioning with bacterial endotoxin has been shown to reduce leukocyte recruitment to the CNS. Systemic infections are known to be associated with the exacerbation of central nervous system (CNS) pathologies such as multiple sclerosis (MS) [1], stroke [2], Parkinson’s and Alzheimer’s diseases [3,4,5]. An increased hepatic APR to brain injury and disease would suggest that any factors that exacerbate the systemic inflammatory response are likely to adversely affect disease outcome [1,10,11,12]. We have shown that the administration of individual exogenous APRs, such as CCL-2, will exacerbate a brain injury model. Pre- and post-conditioning studies suggest that stimulating the immune system can confer a degree of tolerance to CNS injury. The systemic administration of bacterial lipopolysaccharides (LPS) has been reported to confer neuroprotection from a subsequent ischemic challenge [16,17]
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