Prolonged, 24-h delayed peripheral inflammation increases short- and long-term functional impairment and histopathological damage after focal ischemia in the rat
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Updated: Jun 14, 2026
Methods for Acute and Subacute Murine Hindlimb Ischemia
Published on: June 21, 2016
Kristopher D Langdon1, Crystal L Maclellan, Dale Corbett
1Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
Abstract:
The incidence of infection among stroke patients is alarmingly high and both acute and delayed infections increase morbidity and mortality. Experimental studies support the acute clinical data, but little attention has focused on delayed systemic infections. Here, we investigated the effects of prolonged systemic inflammation either before or 24-h after ischemia. Systemic inflammation was induced by injecting rats with three separate doses of lipopolysaccharide (LPS; 50 mug/kg, i.p.) with core temperature monitoring for 48-h after middle cerebral artery occlusion (MCAo). Lipopolysaccharide injected before MCAo increased injury by approximately 30%, whereas delayed injection increased injury by approximately 85% (30-day survival). Proinflammatory cytokines assessed repeatedly for 72 h were significantly and persistently elevated with inflammation. This was accompanied by increases in microglia/macrophage and infiltrating leukocyte numbers in delayed LPS-treated animals. Behavioral assessments at 7 and 30 days revealed approximately 15% deficit in hindlimb function in animals treated with LPS 24-h after ischemia. Clearly, delayed and prolonged postischemic systemic inflammation has devastating effects on stroke outcome, in the absence of a prolonged febrile response. These findings, together with corroborative clinical data, emphasize the importance of early intervention to counteract the deleterious consequences of stroke-associated inflammation and infection.
Insights
Delayed systemic inflammation significantly worsens stroke outcomes. Early intervention is crucial to mitigate the severe effects of post-stroke inflammation and infection on patient recovery and survival.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Stroke-associated infections are common and increase mortality.
- While acute inflammation is studied, delayed systemic infections post-stroke are less understood.
- Systemic inflammation can exacerbate brain injury after stroke.
Purpose of the Study:
- To investigate the impact of prolonged systemic inflammation, induced by lipopolysaccharide (LPS), administered either before or 24 hours after ischemic stroke.
- To analyze the effects of delayed inflammation on stroke severity, survival rates, and neurological deficits.
Main Methods:
- Rats underwent middle cerebral artery occlusion (MCAo) to induce stroke.
- Systemic inflammation was induced using three doses of lipopolysaccharide (LPS).
- Core body temperature, proinflammatory cytokines, immune cell infiltration, and behavioral function were monitored.
Main Results:
- Pre-stroke LPS administration increased injury by ~30%, while post-stroke LPS increased injury by ~85% (30-day survival).
- Delayed LPS treatment led to persistent elevation of proinflammatory cytokines and increased microglia/macrophage and leukocyte infiltration.
- Animals receiving delayed LPS showed a ~15% deficit in hindlimb function at 7 and 30 days post-stroke.
Conclusions:
- Delayed systemic inflammation significantly worsens stroke outcomes and mortality.
- Early intervention is critical to counteract the detrimental effects of post-stroke inflammation.
- These findings highlight the importance of managing inflammation to improve stroke recovery.
