Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment.
Perinatal asphyxia (PA) is able to induce sequelae such as spinal spasticity. Previously, we demonstrated hypothermia as a neuroprotective treatment against cell degeneration triggered by increased nitric oxide (NO) release. Because spinal motoneurons are implicated in spasticity, our aim was to analyze the involvement of NO system at cervical and lumbar motoneurons after PA as well as the application of hypothermia as treatment. PA was performed by immersion of both uterine horns containing full-term fetuses in a water bath at 37 degrees C for 19 or 20 min (PA19 or PA20) or at 15 degrees C for 20 min (hypothermia during PA-HYP). Some randomly chosen PA20 rats were immediately exposed for 5 min over grain ice (hypothermia after PA-HPA). Full-term vaginally delivered rats were used as control (CTL). We analyzed NO synthase (NOS) activity, expression and localization by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity, inducible and neuronal NOS (iNOS and nNOS) by immunohistochemistry, and protein nitrotyrosilation state. We observed an increased NOS activity at cervical spinal cord of 60-day-old PA20 rats, with increased NADPH-d, iNOS, and nitrotyrosine expression in cervical motoneurons and increased NADPH-d in neurons of layer X. Lumbar neurons were not altered. Hypothermia was able to maintain CTL values. Also, we observed decreased forelimb motor potency in the PA20 group, which could be attributed to changes at cervical motoneurons. This study shows that PA can induce spasticity produced by alterations in the NO system of the cervical spinal cord. Moreover, this situation can be prevented by perinatal hypothermia.
Dorfman
Verónica Berta
VB
Laboratorio de Neuropatología Experimental-Instituto de Biología Celular y Neurociencia "Prof. Eduardo De Robertis," Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Rey-Funes
Manuel
M
Bayona
Julio César
JC
López
Ester María
EM
Coirini
Héctor
H
Loidl
César Fabián
CF
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005552:Forelimb / Q000294:innervation; D006801:Humans; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D007231:Infant, Newborn; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology*; D009129:Muscle Tonus; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase