# Baicalein alleviates long-term cognitive impairments induced by repeated neonatal sevoflurane exposure via inhibition of cortical microglial TLR4/NF-kB signaling

## TL;DR

Baicalein helps reduce long-term brain problems in rats caused by early exposure to a common anesthetic by reducing harmful inflammation.

## Contribution

Baicalein's neuroprotective effect is linked to its inhibition of the TLR4/NF-κB pathway in microglia.

## Key findings

- Baicalein reduced sevoflurane-induced cognitive impairments in rats.
- Baicalein inhibited microglial activation and reduced pro-inflammatory mediators.
- Targeting neuroinflammation may prevent early-life anesthesia-related brain injury.

## Abstract

Sevoflurane, a widely used pediatric anesthetic, has been associated with long-term cognitive impairments following repeated neonatal exposure. Baicalein, a flavonoid derived from Scutellaria baicalensis, exhibits neuroprotective and anti-inflammatory properties. This study evaluated whether baicalein can mitigate sevoflurane-induced neuroinflammation and cognitive deficits in developing rats. Neonatal rats were exposed to sevoflurane (3 %, 2 h/day) from postnatal day (P) 6 to P8. In the intervention group, baicalein (50 mg/kg) was administered intraperitoneally from P6 to P8 and orally via drinking water from P21 to P35. Cognitive performance was assessed between P35 and P40 using the open field test, novel object recognition, and fear conditioning paradigms. Brain tissues were collected for Western blot, ELISA, and immunofluorescence analyses. Baicalein treatment significantly attenuated sevoflurane-induced deficits in memory and learning, particularly in the novel object recognition and fear conditioning tasks. Mechanistically, baicalein inhibited microglial activation, reduced cortical expression of TLR4 and phosphorylated NF-κB p65, and decreased pro-inflammatory mediators including iNOS, IL-1β, and IL-6 at P8. These findings indicate that repeated neonatal sevoflurane exposure impairs cognitive function via microglial-mediated neuroinflammation, and that baicalein's neuroprotective effect is at least partly attributable to modulation of cortical microglial activity via TLR4/NF-κB signaling. This study highlights baicalein as a promising therapeutic strategy to prevent long-term neurodevelopmental deficits in neonates.

•Baicalein suppresses microglia-mediated inflammation via the TLR4/NF-κB pathway in neonatal rat cortex.•Repeated neonatal sevoflurane exposures lead to long-term cognitive impairments.•Baicalein significantly alleviates sevoflurane-induced neuroinflammation and cognitive deficits.•Targeting neuroinflammation may offer a novel strategy to mitigate early-life anesthesia-related brain injury.

Baicalein suppresses microglia-mediated inflammation via the TLR4/NF-κB pathway in neonatal rat cortex.

Repeated neonatal sevoflurane exposures lead to long-term cognitive impairments.

Baicalein significantly alleviates sevoflurane-induced neuroinflammation and cognitive deficits.

Targeting neuroinflammation may offer a novel strategy to mitigate early-life anesthesia-related brain injury.