37 - Assessing myelination evolution to study neurorestoration in the neonatal hypoxic-ischemic brain

Poster Number: 37
Publication Number: 37.401

Background: Birth asphyxia and the related hypoxic-ischemic encephalopathy (HIE) continue to cause significant mortality and long-term morbidities. Currently, therapeutic hypothermia (TH) is the only treatment for these neonates in high-income countries. However, it remains often not successful, not efficient in low- and middle-income countries and it does not promote repair. Thus, there is a need to develop alternate therapies targeting brain repair in these neonates to improve their outcomes; one such candidate treatment is sildenafil (Viagra®).

Objective: To assess myelin evolution pattern over the first month of life in the context of HIE, TH and sildenafil.

Design/Methods: We conducted a prospective neuroimaging study of healthy neonates and neonates with HIE treated with TH; a subset of neonates with HIE, who developed brain injury despite TH, received a 7-day treatment of sildenafil given enterally q12h for 14 doses. Brain MRIs were performed around days 2, 10 and 30 of life. We evaluated myelination in eight different regions of interest (ROIs) using a T2* mapping sequence. We compared the T2* values between the neonates without injury (NoBI) (including the healthy neonates and the HIE neonates without brain injury treated only with TH), the HIE neonates with brain injury treated only with TH (BI+TH) and the HIE neonates with brain injury treated with TH and sildenafil (BI+TH/S).

Results: We acquired a total of 176 MRI scans during the first month of life in 9 healthy neonates, 32 NoBI+TH neonates, 25 BI+TH neonates, and 20 BI+TH/S neonates. On day 2 of life, T2* values were significantly increased in all ROIs in all the neonates with injury compared to those without injury. By days 10 and 30 after birth, T2* values remained significantly increased only in the HIE neonates with injury treated only with TH; the HIE neonates with brain injury treated with TH and sildenafil displayed T2* values not anymore significantly different from those without injury by days 10 (all ROIs, except PCC, OR and PWM) and 30 (all ROIs). In addition, by day 30 of life, the HIE neonates with brain injury treated with TH and sildenafil displayed T2* values significantly decreased compared to neonates treated only with TH (all ROIs, except lentiform). As examples, Figures 1 and 2 demonstrated the difference in myelination evolution in the thalamus (Figure 1) and posterior white matter (Figure 2) between the three experimental groups.

Conclusion(s): Myelination was impaired in the neonatal brain after HIE and despite TH. Sildenafil appeared to promote myelination in this context and may thus contribute to brain injury recovery.