Neural injury following stroke: are Toll-like receptors the link between the immune system and the CNS?
Article first published online: 7 MAY 2010
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 160, Issue 8, pages 1872–1888, August 2010
How to Cite
Downes, C. E. and Crack, P. J. (2010), Neural injury following stroke: are Toll-like receptors the link between the immune system and the CNS?. British Journal of Pharmacology, 160: 1872–1888. doi: 10.1111/j.1476-5381.2010.00864.x
- Issue published online: 21 JUL 2010
- Article first published online: 7 MAY 2010
- Received; 20 December 2009; Revised; 24 March 2010; Accepted; 28 March 2010
- toll-like receptors;
- neural inflammation;
The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and complement, chemokines and adhesion molecules that recruit immune cells, and activate glia and microglia. Cerebral ischaemia triggers acute inflammation, which exacerbates primary brain damage. The regulation of inflammation after stroke is multifaceted and comprises vascular effects, distinct cellular responses, apoptosis and chemotaxis. There are many cell types that are affected including neurons, astrocytes, microglia and endothelial cells, all responding to the resultant neuroinflammation in different ways. Over the past 20 years, researchers examining brain tissue at various time intervals after stroke observed the presence of inflammatory cells, neutrophils and monocytes at the site of injury, as well as the activation of endogenous glia and microglia. This review examines the involvement of these cells in the progression of neural injury and proposes that the Toll-like receptors (TLRs) are likely to be an integral component in the communication between the CNS and the periphery. This receptor system is the archetypal pathogen sensing receptor system and its presence and signalling in the brain following neural injury suggests a more diverse role. We propose that the TLR system presents excellent pharmacological targets for the design of a new generation of therapeutic agents to modulate the inflammation that accompanies neural injury.