Lipopolysaccharide worsens the prognosis of experimental cerebral ischemia via interferon gamma-induced protein 10 recruit in the acute stage.

Abstract

BACKGROUND:

Infection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood.

AIMS:

We tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO).

METHODS:

We used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT2 Profiler™ PCR array, and quantitative real-time PCR. The differential genes were subjected to Gene Ontology enrichment analysis and protein-protein interaction (PPI) network construction.

RESULTS:

Lipopolysaccharide profoundly aggravated the brain damage after 24 h post-MCAO. At the acute stage (ischemia/reperfusion 90 min/3 h), the brain homogenate gene expression of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and Interferon gamma-induced protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO + LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO + LPS group, which was also in an important position with degrees of ≥ 14 in PPI network.

CONCLUSIONS:

It was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 h post-MCAO.

• Authors: Ping Wang, Jiaqi Zhang, Feifei Guo, Shuang Wang, Yi Zhang, Defeng Li, Haiyu Xu, Hongjun Yang
• Journal: BMC neuroscience (BMC Neurosci) Vol. 20 Issue 1 Pg. 64 (12 27 2019) ISSN: 1471-2202 [Electronic] England
• PMID: 31881846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL10
• Cxcl10 protein, rat
• IL1B protein, rat
• Il6 protein, rat
• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Brain (metabolism, pathology)
• Brain Ischemia (diagnosis, metabolism, pathology)
• Cerebrovascular Circulation (physiology)
• Chemokine CXCL10 (metabolism)
• Inflammation (diagnosis, metabolism, pathology)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Lipopolysaccharides
• Male
• Prognosis
• Random Allocation
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (metabolism)