Dexmedetomidine alleviates neurobehavioral impairments and myelination deficits following lipopolysaccharide exposure in early postnatal rats.

AIMS: White matter injury (WMI) is the main form of brain injury in preterm neonate survivors, and perinatal inflammation is implicated in the pathogenesis of WMI. It has been demonstrated that dexmedetomidine, an anesthetic adjuvant, possesses neuroprotective effects in both preclinical and clinical trials. The present study was conducted to explore whether dexmedetomidine could protect against neurobehavioral impairments and myelination deficits caused by lipopolysaccharide (LPS) exposure in the early postnatal rat brain.

MAIN

METHODS

LPS (2 mg/kg) was intraperitoneally (i.p.) injected in Sprague-Dawley rat pups on postnatal day 2 (P2). Dexmedetomidine (25 μg/kg) or vehicle was given i.p. immediately after LPS injection. STAT3 and p-STAT3 expression were detected by western blot in rat brain 24 h after drug administration. Immunostaining for GFAP to was performed to evaluate astrocytic response at 24 h post-LPS and P14. Neurobehavioral tests (the righting reflex, negative geotaxis, and wire hanging maneuver tests) were performed from P5 to P10. Histological analysis of myelin content was accessed by immunohistochemistry for CNPase and MBP at P14.

KEY FINDINGS: Our results showed that treatment with dexmedetomidine significantly ameliorated LPS-induced neurobehavioral abnormalities and myelin damage, which is accompanied by suppression of STAT3 activation and reactive astrogliosis.

SIGNIFICANCE: Dexmedetomidine can alleviate neurobehavioral impairments and myelination deficits after LPS exposure in early postnatal rats, probably by mitigating STAT3-mediated reactive astrogliosis. Our results suggest that dexmedetomidine might be a promising agent to treat brain injury in neonates.