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Prophylactic progesterone prevents adverse behavioural and neurocognitive effects of neonatal anaesthesia exposure in
Bushra Wali1, Iqbal Sayeed1, Donald G Stein2
1Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Insights
Progesterone treatment before general anesthesia exposure protected young rats from long-term neurocognitive and behavioral deficits. This finding suggests progesterone may shield the developing brain from anesthesia-induced harm.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Early exposure to general anesthesia is linked to neurocognitive deficits and anxiety.
- Millions of children undergo anesthesia annually, necessitating protective strategies for the developing brain.
Purpose of the Study:
- To investigate if progesterone administration before general anesthesia can prevent long-term neurocognitive and behavioral changes.
- To assess the neuroprotective potential of progesterone against anesthesia-induced developmental effects.
Main Methods:
- Long-Evans rat pups were exposed to sevoflurane (anesthetic) or control conditions at critical developmental stages.
- Progesterone or vehicle was administered subcutaneously prior to anesthesia exposure.
- Neurobehavioral and cognitive functions were assessed using the elevated plus maze and Morris water maze.
Main Results:
- Progesterone treatment attenuated the inflammatory chemokine (CXCL1) response to sevoflurane.
- Rats exposed to anesthesia without progesterone showed increased anxiety and impaired learning/memory.
- Progesterone-treated rats did not exhibit these deficits, performing similarly to controls.
Conclusions:
- Progesterone mitigated anesthesia-induced inflammation and prevented cognitive/behavioral impairments.
- Pre-anesthesia progesterone treatment shows promise in protecting the developing brain from anesthesia-related harm.
Background:
Evidence from animal models and human studies suggests an association between early general anaesthesia exposure and development of long-lasting neurocognitive problems including learning and memory impairments and an anxious phenotype. Because millions of children each year undergo procedures that require anaesthesia, it is important to investigate ways to protect the vulnerable developing brain. We evaluated whether progesterone treatment administered before general anaesthesia exposure could prevent long-term anaesthesia-induced neurocognitive and behavioural changes.
Methods:
Female and male Long-Evans rat pups were repeatedly exposed to 2 h of sevoflurane or control procedures at postnatal days 7, 10, and 13. Subcutaneous injections of progesterone or vehicle were administered immediately before general anaesthesia exposure or control procedures. Neurobehavioural and cognitive outcomes were evaluated using elevated plus maze and Morris water maze tests.
Results:
Prophylactic progesterone treatment attenuated the chemokine (C-X-C motif) ligand 1 (CXCL1) response to sevoflurane exposure. Rats given vehicle treatment with general anaesthesia exposure exhibited increased anxiety on the elevated plus maze and learning and memory impairments on the Morris water maze. However, rats treated with progesterone before general anaesthesia lacked these impairments and performed in a similar manner to controls on both tasks.
Conclusions:
Progesterone attenuated the anaesthesia-induced, acute peripheral inflammatory response and prevented cognitive and behavioural alterations associated with early repeated general anaesthesia exposure. Importantly, our results suggest that progesterone treatments given before general anaesthesia may help to protect the developing brain.
