Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The CNS inflammatory response is regulated by hepatic chemokine synthesis, which promotes leukocytosis and facilitates leukocyte recruitment to the site of injury. To understand the role of the individual cell populations in the liver during the hepatic response to acute brain injury, we selectively depleted Kupffer cells (KC), using clodronate-filled liposomes, and assessed the inflammatory response following a microinjection of IL-1beta into the rat brain or after a compression injury in the spinal cord. We show by immunohistochemistry that KC depletion reduces neutrophil infiltration into the IL-1beta-injected brain by 70% and by 50% into the contusion-injured spinal cord. qRT-PCR analysis of hepatic chemokine mRNA expression showed that chemokine expression in the liver after brain injury is not restricted to a single cell population. In non-depleted rats, CXCL-10, IL-1beta, CCL-2, and MIP-1alpha mRNAs were increased up to sixfold more than in KC depleted rats. However, CXCL-1 and MIP-1beta were not significantly affected by KC depletion. The reduction in chemokine mRNA expression by the liver was not associated with decreased neutrophil mobilisation as might have been expected. These findings suggest that in response to CNS injury, KC mediated mechanisms are responsible for increasing neutrophil entry to the site of CNS injury, but that neutrophil mobilisation is dependent on other non-KC mediated events. However, the suppression of KC activity may prevent secondary damage after acute brain injury.

Original publication

DOI

10.1016/j.neuropharm.2008.06.074

Type

Journal article

Journal

Neuropharmacology

Publication Date

10/2008

Volume

55

Pages

780 - 787

Keywords

Analysis of Variance, Animals, Bone Density Conservation Agents, Brain Injuries, Chemokines, Clodronic Acid, Disease Models, Animal, Encephalitis, Interleukin-1beta, Kupffer Cells, Liposomes, Male, Myelitis, RNA, Messenger, Rats, Rats, Wistar, Spinal Cord Injuries, Time Factors