<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto"
id="d2862780e125">Neonatal hypoxic ischemic encephalopathy (HIE) is a neurological
disease caused by
restricted oxygen and blood flow to the brain at or around the time of birth. Long
term cognitive and motor sequelae are common and demonstrate sexual dimorphism in
animal studies. Therapeutic hypothermia (TH) is the standard of care for HIE, but
provides incomplete neuroprotection. Using the Vannucci model of neonatal HIE, term-equivalent
11-day old rat pups were subjected to mild-moderate hypoxic-ischemic injury (HII),
and a subset of animals were treated with TH. Sex-dependent neuroprotection was measured
with gross and fine motor control assays, and functional deficits detected with these
assays were correlated to injury in specific brain structures. At the equivalent of
human adolescence and adulthood (P51-89), accelerod and beam walking tests were used
to assess gross motor function, and string-pulling and food handling tests were used
to assess fine motor function. At necropsy (P94-97), brain lesions were primarily
focused to the posterior cerebrum and characterized by variable reduction in cortical,
thalamic and hippocampal regions and glial scarring. Gross motor impairment was detected
in male rats with untreated and TH-treated HIE in the accelerod test, but beam walk
test data was confounded by the lower body mass of untreated male rats. HIE animals
of both sexes demonstrated deficit in the forelimb contralateral to ischemic surgery,
observed as unilaterally impaired food handling behaviors, and in string pulling as
decreased string contacts and increased in bracing behavior. However, kinematic analyses
revealed sex-specific decreases in peak speeds in string reaching and pulling movements.
In both sexes, treatment with TH improved body mass, some measures of contralateral
forelimb impairment, and the severity of brain lesions to levels not different to
Sham surgery rats. Unique differences in behavior following TH were observed in female
rats, who took longer to consume food items but traversed beams and approached strings
faster than untreated and Sham females. Future use of these motor assays may unravel
the subtle, sex-specific differences in HIE outcomes and in developing a customized
therapeutic approach to neonatal brain injury.
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