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Updated: May 17, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
Post-stroke infections exacerbate ischemic brain injury in middle-aged rats: immunomodulation and neuroprotection by
1Department of Emergency Medicine, Brain Research Laboratory, Emory University, Atlanta, GA 30322, USA.
Abstract:
We investigated the effect of delayed, prolonged systemic inflammation on stroke outcomes and progesterone (P4) neuroprotection in middle-aged rats. After transient middle cerebral artery occlusion/reperfusion (MCAO) surgery, rats received P4 (8 or 16 mg/kg) or vehicle injections at 2h, 6h and every 24h until day 7 post-occlusion. At 24h post-injury systemic inflammation was induced by giving three doses of lipopolysaccharide (LPS; 50 μg/kg, at 4h intervals) to model post-stroke infections. We measured serum brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines, and behavioral parameters at multiple times. Serum BDNF levels decreased more in the vehicle+LPS group compared to vehicle-alone at 3 and 7 days post-injury (P<0.05). Vehicle-alone showed a significant increase in interleukin-1β, interleukin-6, and tumor necrosis factor alpha levels at different times following stroke and these levels were further elevated in the vehicle+LPS group. P4 at both doses produced a significant (P<0.05) decline in cytokine levels compared to vehicle and vehicle+LPS. P4 restored BDNF levels at 3 and 7 days post-stroke (P<0.05). Behavioral assessment (rotarod, grip strength, sensory neglect and locomotor activity tests) at 3, 5 and 7 days post-stroke revealed that the vehicle group had significant (P<0.05) deficits in all tests compared to intact controls, and performance was worse in the vehicle+LPS group. P4 at both doses produced significant functional improvement on all tests. Systemic inflammation did not show an additive effect on infarct volume but P4 at both doses showed significant infarct reduction. We suggest that post-stroke infection exacerbates stroke outcomes and P4 exerts neuroprotective/modulatory effects through its systemic anti-inflammatory and BDNF regulatory actions.
Insights
Post-stroke infections worsen outcomes, but progesterone (P4) treatment improves recovery by reducing inflammation and boosting brain-derived neurotrophic factor (BDNF). This study highlights P4
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Systemic inflammation following stroke can worsen neurological outcomes.
- Progesterone (P4) has shown neuroprotective potential, but its effects on inflammation-induced stroke complications are not fully understood.
Purpose of the Study:
- To investigate the impact of delayed systemic inflammation on stroke outcomes and the neuroprotective effects of progesterone (P4) in a rat model.
- To assess P4's ability to modulate inflammatory markers and brain-derived neurotrophic factor (BDNF) levels post-stroke.
Main Methods:
- Middle cerebral artery occlusion/reperfusion (MCAO) surgery was performed on middle-aged rats.
- Systemic inflammation was induced using lipopolysaccharide (LPS) at 24 hours post-stroke.
- Rats received varying doses of P4 or vehicle, and outcomes were assessed via behavioral tests, cytokine analysis, and BDNF levels.
Main Results:
- Lipopolysaccharide (LPS) administration significantly increased pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor alpha) and decreased serum BDNF levels.
- Progesterone (P4) treatment significantly reduced cytokine levels and restored BDNF levels.
- P4 administration improved functional recovery in behavioral tests and reduced infarct volume, despite systemic inflammation.
Conclusions:
- Post-stroke systemic inflammation exacerbates stroke outcomes and neurological deficits.
- Progesterone (P4) demonstrates significant neuroprotective and modulatory effects by counteracting inflammation and regulating BDNF.
- P4 holds therapeutic potential for managing stroke patients, particularly those experiencing post-stroke infections.