Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

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Purpose The optimal management of CSF drainage in acute hydrocephalus, in particular when to initiate drain weaning, remains uncertain. This study aimed to evaluate the impact of timing and method of drain weaning on patient outcomes. Methods This prospective observational study in a large-volume tertiary neuroscience centre including all adult patients who required temporary CSF drainage for acute hydrocephalus of any cause, between January 2020 and March 2021. Contemporaneous data collection was conducted, including patient demographics, time to clamp, weaning methods, and clinical outcomes of hospital length of stay (LOS), rate of shunt insertion, drain-related infections, and mechanical complications. Univariate and multivariate statistical analyses were performed to identify the independent associations of timing-related factors. Results 69 patients were included (mean age = 59.4 years). 59% had CSF diversion for aneurysmal subarachnoid haemorrhage, and 88% had EVD drainage. The length of drainage prior to the first clamp was significantly associated with overall length of drainage (p<0.0001), LOS (p=0.004) and time to shunt (p=0.02) following multivariate adjustment. For each day delayed in initiating the drain challenge, the overall LOS increased by an additional 1.25 days. There was no association between weaning method and LOS, the rate of shunting, or CNS infection, however those in the gradually weaned group had more mechanical complications such as drain blockage or CSF leakage than those rapidly weaned (p = 0.03) after adjustment. Discussion The study recommends challenging the drain early, via a rapid wean, to reduce LOS, mechanical complications, and possibly infections. The consequences of temporary CSF diversion have significant implications at financial and patient levels, but the quality of evidence regarding weaning remains poor. Further randomized multi-center studies and national databases of practice are required to allow definitive conclusions to be drawn.