Published Online
on September 16, 2004

A more recent version of this article appeared on November 1, 2004

This Article Full Text (PDF) All Versions of this Article: 35/11/2576    most recent 01.STR.0000143450.04438.aev1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosenzweig, H. L. Articles by Stenzel-Poore, M. P. Search for Related Content PubMed PubMed Citation Articles by Rosenzweig, H. L. Articles by Stenzel-Poore, M. P. Pubmed/NCBI databases Substance via MeSH Related Collections Animal models of human disease Ischemic biology - basic studies Acute Cerebral Infarction

Submitted on May 17, 2004
Revised on July 14, 2004
Accepted on August 6, 2004

Endotoxin Preconditioning Prevents Cellular Inflammatory Response During Ischemic Neuroprotection in Mice

Holly L. Rosenzweig BA; Nikola S. Lessov MD; David C. Henshall PhD; Manabu Minami MD, PhD; Roger P. Simon MD; and Mary P. Stenzel-Poore PhD^*

From the Department of Molecular Microbiology and Immunology (H.L.R., M.P.S.-P.) and the Oregon Stroke Center (N.S.L.), Oregon Health and Science University, Portland; and Robert S. Dow Neurobiology Laboratories (D.C.H., M.M., R.P.S.), Legacy Research, Portland, Ore.

^* To whom correspondence should be addressed. E-mail: poorem{at}ohsu.edu.

Background and Purpose--Tolerance to ischemic brain injury is induced by several preconditioning stimuli, including lipopolysaccharide (LPS). A small dose of LPS given systemically confers ischemic protection in the brain, a process that appears to involve activation of an inflammatory response before ischemia. We postulated that LPS preconditioning modulates the cellular inflammatory response after cerebral ischemia, resulting in neuroprotection.

Methods--Mice were treated with LPS (0.2 mg/kg) 48 hours before ischemia induced by transient middle cerebral artery occlusion (MCAO). The infarct was measured by 2,3,5-triphenyltetrazolium chloride staining. Microglia/macrophage responses after MCAO were assessed by immunofluorescence and flow cytometry. The effect of MCAO on white blood cells in the brain and peripheral circulation was measured by flow cytometry 48 hours after MCAO.

Results--LPS preconditioning induced significant neuroprotection against MCAO. Administration of low-dose LPS before MCAO prevented the cellular inflammatory response in the brain and blood. Specifically, LPS preconditioning suppressed neutrophil infiltration into the brain and microglia/macrophage activation in the ischemic hemisphere, which was paralleled by suppressed monocyte activation in the peripheral blood.

Conclusions--LPS preconditioning induces neuroprotection against ischemic brain injury in a mouse model of stroke. LPS preconditioning suppresses the cellular inflammatory response to ischemia in the brain and circulation. Diminished activation of cellular inflammatory responses that ordinarily exacerbate ischemic injury may contribute to neuroprotection induced by LPS preconditioning.

Key words: cerebral ischemia, focal • inflammation • leukocytes • mice • microglia

This article has been cited by other articles:

				S. Malaeb and O. Dammann Fetal Inflammatory Response and Brain Injury in the Preterm Newborn J Child Neurol, September 1, 2009; 24(9): 1119 - 1126. [Abstract] [PDF]

				B. Marsh, S. L. Stevens, A. E. B. Packard, B. Gopalan, B. Hunter, P. Y. Leung, C. A. Harrington, and M. P. Stenzel-Poore Systemic Lipopolysaccharide Protects the Brain from Ischemic Injury by Reprogramming the Response of the Brain to Stroke: A Critical Role for IRF3 J. Neurosci., August 5, 2009; 29(31): 9839 - 9849. [Abstract] [Full Text] [PDF]

				Z. TAIRA, H. MONMASU, and Y. UEDA Innate Host-defensive Function of a Hepatic Lipid Fraction Produced in Low-dose Carbon Tetrachloride-pretreated Mice Anticancer Res, March 1, 2009; 29(3): 837 - 841. [Abstract] [Full Text] [PDF]

				R. E. Hulse, W. G. Swenson, P. E. Kunkler, D. M. White, and R. P. Kraig Monomeric IgG Is Neuroprotective via Enhancing Microglial Recycling Endocytosis and TNF-{alpha} J. Neurosci., November 19, 2008; 28(47): 12199 - 12211. [Abstract] [Full Text] [PDF]

				P. J. Franco, D. C. Fernandez, P. H. Sande, M. I. Keller Sarmiento, M. Chianelli, D. A. Saenz, and R. E. Rosenstein Effect of Bacterial Lipopolysaccharide on Ischemic Damage in the Rat Retina Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4604 - 4612. [Abstract] [Full Text] [PDF]

				T. P. Obrenovitch Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia Physiol Rev, January 1, 2008; 88(1): 211 - 247. [Abstract] [Full Text] [PDF]

				E. J. Hickey, X. You, V. Kaimaktchiev, M. Stenzel-Poore, and R. M. Ungerleider Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1588 - 1596. [Abstract] [Full Text] [PDF]

				A. Chamorro, X. Urra, and A. M. Planas Infection After Acute Ischemic Stroke: A Manifestation of Brain-Induced Immunodepression Stroke, March 1, 2007; 38(3): 1097 - 1103. [Abstract] [Full Text] [PDF]

				M. P. Stenzel-Poore, S. L. Stevens, J. S. King, and R. P. Simon Preconditioning Reprograms the Response to Ischemic Injury and Primes the Emergence of Unique Endogenous Neuroprotective Phenotypes: A Speculative Synthesis Stroke, February 1, 2007; 38(2): 680 - 685. [Abstract] [Full Text] [PDF]