Nitric Oxide Production in the Striatum and Cerebellum of a Rat Model of Preterm Global Perinatal Asphyxia

Melinda Barkhuizen, WDJ van de Berg, Jan de Vente, Carlos Blanco, Danilo Gavilanes, Harry Steinbusch

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7 Citations (Scopus)


Encephalopathy due to perinatal asphyxia (PA)
is a major cause of neonatal morbidity and mortality in
the period around birth. Preterm infants are especially at
risk for cognitive, attention and motor impairments.
Therapy for this subgroup is limited to supportive care,
and new targets are thus urgently needed. Post-asphyxic
excitotoxicity is partially mediated by excessive nitric oxide
(NO) release. The aims of this study were to determine
the timing and distribution of nitric oxide (NO) production
after global PA in brain areas involved in motor
regulation and coordination. This study focused on the rat
striatum and cerebellum, as these areas also affect cognition
or attention, in addition to their central role in motor
control. NO/peroxynitrite levels were determined empirically
with a fluorescent marker on postnatal days P5, P8
and P12. The distributions of neuronal NO synthase
(nNOS), cyclic guanosine monophosphate (cGMP),
astroglia and caspase-3 were determined with immunohistochemistry.
Apoptosis was additionally assessed by measuring
caspase-3-like activity from P2-P15. On P5 and P8,
increased intensity of NO-associated fluorescence and
cGMP immunoreactivity after PA was apparent in the striatum,
but not in the cerebellum. No changes in nNOS
immunoreactivity or astrocytes were observed. Modest
changes in caspase-3-activity were observed between
groups, but the overall time course of apoptosis over the
first 11 days of life was similar between PA and controls.
Altogether, these data suggest that PA increases NO/
peroxynitrite levels during the first week after birth within
the striatum, but not within the cerebellum, without
marked astrogliosis. Therapeutic benefits of interventions
that reduce endogenous NO production would likely be
greater during this time frame.
Original languageEnglish
Pages (from-to)400-409
JournalNeurotoxicity Research
Issue number3
Publication statusPublished - 30 Apr 2017


  • Asphyxia . Nitrosidative stress .cGMP .Neuronal

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