Low-dose lipopolysaccharide injection prior to subarachnoid hemorrhage modulates Delayed Deterioration associated with vasospasm in subarachnoid hemorrhage.
There is increasing evidence that inflammation plays a role in the development of Delayed Deterioration associated with vasospasm (DDAV) after subarachnoid hemorrhage (SAH). Lipopolysaccharide (LPS) is an activator of the innate inflammatory system that causes DDAV in animal models. The effect of low-dose LPS has been shown to be protective in stroke models but has not been investigated in SAH. Two treatments were studied: (1) a single intraperitoneal dose of 0.6 mg/kg injected 24 h prior to SAH and (2) four daily doses administered prior to SAH. DDAV was determined by India ink angiography at day 6; behavioral testing was done in a different cohort of animals, and analysis of brain chemokine levels was accomplished by dot blot. Vessel caliber was improved compared to the SAH group in the single-injection group (ldLPS ×1) (p < 0.05). In the multiple-injection group (ldLPS ×4), the vessel caliber was similar to SAH (p < 0.05). ldLPS ×1 improved performance on the Barnes maze test, whereas the ldLPS ×4 was worse (p < 0.001). Brain levels of the inflammatory chemokine KC (keratinocyte-derived chemokine) were decreased in the ldLPS ×1 and increased in the ldLPS ×4 group. Single-injection low-dose LPS preconditioning was protective for delayed deterioration associated with vasospasm (DDAV), whereas the multiple-injection course exacerbated DDAV. This further supports that inflammation plays an important role in the development of DDAV, and that modulating the inflammatory system may be a potential target for future therapies in SAH.
Department of Neurosurgery, Cleveland Clinic, Cleveland, OH, USA. smithas@ccf.org
Saksith
S
Smithason
Shari K
SK
Moore
J Javier
JJ
Provencio
D000704:Analysis of Variance; D000818:Animals; D001921:Brain; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002244:Carbon; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000517:prevention & control*
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; C028433:chinese ink; D018799:Intercellular Adhesion Molecule-1; D002244:Carbon