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Understanding sedative effects within the context of acute neuroinflammation in the developing brain: Potential

Amanda Furman1, Nikki Miller Ferguson2, Audrey D Lafrenaye3

  • 1Department of Physical Medicine and Rehabilitation, Richmond, VA, United States.

Experimental Neurology
|June 11, 2023
PubMed

Insights

Pediatric critical illness can cause delirium. Combining inflammation with opioid and benzodiazepine sedation in young rats worsened delirium-like behaviors and altered neuroinflammation markers.

Area of Science:

  • Neuroscience
  • Pediatric Critical Care
  • Pharmacology

Background:

  • Neurologic morbidity is common in critically ill children.
  • Opioid and benzodiazepine sedation is a risk factor for delirium and long-term issues.
  • The interaction between multidrug sedation and brain inflammation in pediatric critical illness is understudied.

Purpose of the Study:

  • To investigate the combined effects of inflammation and multidrug sedation (opioids and benzodiazepines) on neuroinflammation and delirium-like behaviors in developing rats.
  • To understand the impact on neuroimmune responses and neurodevelopment.

Main Methods:

  • Mild-moderate inflammation was induced using lipopolysaccharide (LPS) in weanling rats.
  • Rats received repeated opioid (morphine) and benzodiazepine (midazolam) sedation.
  • Delirium-like behaviors were assessed using a composite z-score, and neuroinflammatory markers (Iba1, GFAP) and cytokines were measured in brain homogenates.

Main Results:

  • LPS, MorMdz, or LPS/MorMdz treatments significantly increased delirium-like behaviors compared to controls.
  • While LPS alone increased neuroinflammatory markers and cytokines, co-administration with MorMdz did not show the same increase.
  • Specifically, ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expression was higher after LPS than LPS/MorMdz.

Conclusions:

  • Combined inflammation and multidrug sedation in developing rats exacerbates delirium-like behaviors.
  • This combination may modulate the neuroinflammatory response, potentially masking some effects of inflammation alone.
  • Findings highlight the need to consider sedation's impact on neuroimmune responses in pediatric critical illness.

Keywords:
BenzodiazepineDeliriumIntensive care sedationJuvenile ratLipopolysaccharideNeurodevelopmentNeuroinflammationOpioidProinflammatory cytokinesSedative neurotoxicity

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