Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia

Abstract

Objective Birth asphyxia (BA) is the most frequent cause of neonatal death as well as central nervous system (CNS) injury. BA is often associated with neonatal seizures, which only poorly respond to anti‐seizure medications and may contribute to the adverse neurodevelopmental outcome. Using a non‐invasive rat model of BA, we have recently reported that the potent benzodiazepine, midazolam, prevents neonatal seizures in ~50% of rat pups. In addition to its anti‐seizure effect, midazolam exerts anti‐inflammatory actions, which is highly relevant for therapeutic intervention following BA. The 2 major aims of the present study were to examine (1) whether midazolam reduces the adverse outcome of BA, and (2) whether this effect is different in rats that did or did not exhibit neonatal seizures after drug treatment. Methods Behavioral and cognitive tests were performed over 14 months after asphyxia, followed by immunohistochemical analyses. Results All vehicle‐treated rats had seizures after asphyxia and developed behavioral and cognitive abnormalities, neuroinflammation in gray and white matter, neurodegeneration in the hippocampus and thalamus, and hippocampal mossy fiber sprouting in subsequent months. Administration of midazolam (1 mg/kg i.p.) directly after asphyxia prevented post‐asphyctic seizures in ~50% of the rats and resulted in the prevention or decrease of neuroinflammation and the behavioral, cognitive, and neurodegenerative consequences of asphyxia. Except for neurodegeneration in the thalamus, seizures did not seem to contribute to the adverse outcome of asphyxia. Interpretation The disease‐modifying effect of midazolam identified here strongly suggests that this drug provides a valuable option for improving the treatment and outcome of BA. ANN NEUROL 2023;93:226–243

The Application Value of Combined Detection of Serum IL-6, LDH, S100, NSE, and GFAP in the Early Diagnosis of Brain Damage Caused by Neonatal Asphyxia

“…Neonatal asphyxia is a severe pathological condition that occurs when various factors disrupt the exchange of gases between the mother and fetus, resulting in oxygen deprivation and the inability to establish and maintain normal breathing after birth, which can lead to cerebral hypoxia ( 1 ). The neonatal brain has a high metabolic rate and requires significant oxygen for proper functioning.…”