Minocycline Mitigates Sepsis-Induced Neuroinflammation and Promotes Recovery in Mice: Insights into Neuroprotection and Inflammatory Modulation

Abstract

Aim: Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, particularly within the brain, was investigated in this study for its protective effects against sepsis-induced brain injury. Methods: Adult male C57 mice received pretreatment with varying doses of minocycline (12.5, 25, and 50 mg/kg) three days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Results: Septic mice exhibited significant weight loss and impaired spontaneous locomotor activity. Initially, minocycline did not attenuate the severity of weight loss (1 day) or locomotor activity impairment (4 hours post-sepsis), but it significantly accelerated the recovery of the mice in later days. Sepsis led to elevated mRNA expression of IL-1β and TNF-α, increased MDA levels, and decreased thiol content and SOD activity 24 hours after sepsis induction. Minocycline dose-dependently mitigated brain inflammation and oxidative stress damage. Conclusion: Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications.