Abstract
Aim: previous studies have demonstrated nitric oxide toxicity in neonatal hypoxic-ischemic brain injury. Although neonatal hypoxic-ischemic injury of the spinal cord has been reported, pathways of spinal cord injury have not been studied in detail, but may well be relevant for neuroprotective strategies. In the present study, we examined the presence of nitrotyrosine (indicating nitric oxide toxicity), activated caspase-3 (indicating apoptosis), and activated microglia and macrophages (CD-68) in spinal cord tissue of asphyxiated fullterm neonates. Parental informed consent was obtained, and studies were approved by the Ethics Committee of the University Medical Center Utrecht.
Patients, methods: studies were performed in 18 fullterm neonates who died within the first week of life after perinatal asphyxia. All has severe hypoxic-ischemic encephalopathy and multiple organ failure. Histological examinations were performed at three levels of the spinal cord, and included in addition to hematoxylin-eosin (HE) staining for nitrotyrosine, activated caspase-3 and CD-68. Staining was scored on a 3-point scale from 0 (none) to 3 (massive).
Results: nitrotyrosine (score >= 1) was present in 5/18, activated caspase 3 (score >= 1) was present in 8/18 (white matter), 4/18 (motor neurons), and CD-68 (score >= 1) in 3/18 (white and gray matter). Nitrotyrosine staining correlated positively with caspase-3 (P< 0.05). Nitrotyrosine was most prominent in the neonates who died within 24 hours after birth, as was activated caspase-3. CD-68 was demonstrated only after 24 hours. Routine HE staining did not show abnormalities.
Conclusion: HE staining was normal, but activated caspase-3, nitrotyrosine and CD-68 could be demonstrated in spinal cord tissue of some asphyxiated fullterm neonates. Neuroprotective strategies for asphyxiated fullterm neonates should also aim at the spinal cord. This study was funded by the 'Dr.W.M. Phelps-Stichting voor Spastici', Bussum, the Netherlands.
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Groenendaal, F., Lammers, H. & Nikkels, P. 156 Nitrotyrosine, Activated Caspase-3, and CD-68 in the Spinal Cord of Asphyxiated Fullterm Neonates. Pediatr Res 58, 381 (2005). https://doi.org/10.1203/00006450-200508000-00185
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DOI: https://doi.org/10.1203/00006450-200508000-00185