Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neonatology 2008;93:1–6 DOI: 10.1159/000106432 Nitrotyrosine in Human Neonatal Spinal Cord after Perinatal Asphyxia Floris Groenendaal a Johannes Vles c Harry Lammers b Jan De Vente d Diane Smit a Peter G.J. Nikkels b Departments of a Neonatology and b Pathology, University Medical Center Utrecht, Utrecht, and Departments of c Pediatric Neurology and d Psychiatry and Neuropsychology, University Hospital, Maastricht, The Netherlands Introduction Excessive nitric oxide (NO) production appears to play an important role in perinatal hypoxic-ischemic brain in- jury [1–5]. Both formation of nitrotyrosine (NT), as well as direct effects of NO on mitochondrial function are im- portant [6, 7]. In addition, NO may contribute to inflam- matory responses [7]. More than 20 years ago, spinal cord injury after peri- natal hypoxia-ischemia has been demonstrated [8, 9]. This spinal cord injury may contribute to the clinical pic- ture of hypoxic-ischemic encephalopathy (HIE). Unfor- tunately, the severity of spinal cord injury is difficult to assess by physical examination because most infants with HIE and seizures are treated with high doses of antiepi- leptic drugs which contribute to hypotonia. At present it is unknown whether excessive NO pro- duction is involved in spinal cord injury after perinatal hypoxia-ischemia. Knowledge of these pathways leading to pathology is important for the development of ade- quate neuroprotective strategies, such as whole-body hy- pothermia [10] . We examined spinal cord changes of full-term neo- nates who died during the first week of life after severe perinatal hypoxia-ischemia to study NO production and inflammation. Key Words Neonates, spinal cord changes  Spinal cord  Hypoxia-ischemia  Nitric oxide  Inflammation  Nitrotyrosine Abstract Background: Spinal cord injury has been reported after perinatal asphyxia in full-term neonates. Objectives: To ex- amine the role of excessive nitric oxide production in perina- tal spinal cord injury. Subjects and Methods: Tissue samples of 18 full-term neonates who died of hypoxic-ischemic en- cephalopathy were analyzed for the presence of nitrotyro- sine (NT). Results: NT was demonstrated in 5 of these 18 neonates. In addition, activated caspase 3, a marker of apo- ptosis, and CD68, as a marker of inflammation, could be demonstrated in some infants. Conclusions: excessive nitric oxide production and subsequent NT formation is seen in spinal cord tissue after severe perinatal asphyxia. This find- ing may be relevant for the development of neuroprotective strategies. Copyright © 2007 S. Karger AG, Basel Received: January 16, 2007 Accepted: May 9, 2007 Published online: July 25, 2007 formerly Biology of the Neonate Dr. Floris Groenendaal Department of Neonatology, Room KE 04.123.1 Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Lundlaan 6 NL–3584 EA Utrecht (The Netherlands) Tel. +31 30 250 4545, Fax +31 30 250 5320, E-Mail F.Groenendaal@umcutrecht.nl © 2007 S. Karger AG, Basel 1661–7800/08/0931–0001$24.50/0 Accessible online at: www.karger.com/neo