Immuno-modulator inter-alpha inhibitor proteins ameliorate complex auditory processing deficits in rats with neonatal hypoxic-ischemic brain injury

- Neonatal HI is linked to auditory processing deficits in humans and rodent models.
- Subjects with HI injury and those with HI and IAIP had reductions in brain weight.
- HI subjects regardless of treatment showed basic auditory acuity (gap detection)
- IAIP prevented complex tone-order discrimination impairments in HI subjects.

Hypoxic-ischemic (HI) brain injury is recognized as a significant problem in the perinatal period, contributing to life-long language-learning and other cognitive impairments. Central auditory processing deficits are common in infants with hypoxic-ischemic encephalopathy and have been shown to predict language learning deficits in other at risk infant populations. Inter-alpha inhibitor proteins (IAIPs) are a family of structurally related plasma proteins that modulate the systemic inflammatory response to infection and have been shown to attenuate cell death and improve learning outcomes after neonatal brain injury in rats. Here, we show that systemic administration of IAIPs during the early HI injury cascade ameliorates complex auditory discrimination deficits as compared to untreated HI injured subjects, despite reductions in brain weight. These findings have significant clinical implications for improving central auditory processing deficits linked to language learning in neonates with HI related brain injury.