Sensory deficits and olfactory system injury detected by novel application of MEMRI in newborn rabbit after antenatal hypoxia-ischemia.
Sensory deficits are frequently observed in cerebral palsy patients. The motor response to smell was found to be abnormal in an animal model of cerebral palsy following fetal hypoxia-ischemia. We hypothesized that fetal hypoxia-ischemia causes long-lasting and selective olfactory tract injury. A population of newborn rabbits with motor deficits was selected after spontaneous delivery following uterine ischemia at 22 days gestation (E22, 70% term). MnCl(2), 20 mg/kg, was administered in both nostrils at postnatal day 1 (E32). One nostril was occluded to control for smell augmentation through the other open nostril by intermittent amyl acetate stimulation for 6 h. T1-weighted MRI images were obtained on newborn rabbits. Amyl acetate exposure increased augmentation of Mn(2+) uptake in olfactory epithelium on the open side in control group but the augmentation was decreased after hypoxia. The proportion of animals with a greater enhancement in the open side increased in controls after amyl acetate, but not in hypoxia. Mn(2+) took longer to arrive at the olfactory bulbs and the rate of subsequent increase was slower in hypoxia. Concomitantly, the thickness of olfactory epithelium and the number of mature olfactory neurons, detected on olfactory marker protein immunostaining, were significantly less in the hypoxic group. Functional MRI studies are superior to neurobehavioral smell testing in the rabbit kits as they are more sensitive and quantifiable measures and do not depend upon the motor response. Antenatal hypoxia-ischemia causes long-lasting injury to neuronal tracts of the olfactory system including olfactory epithelium.
Drobyshevsky
Alexander
A
Department of Pediatrics, Evanston Northwestern Healthcare Research Institute and Northwestern University, 2650 Ridge Avenue, Evanston, IL 60201, USA. oldrobys@northwestern.edu
Robinson
Alan M
AM
Derrick
Matthew
M
Wyrwicz
Alice M
AM
Ji
Xinhai
X
Englof
Ila
I
Tan
Sidhartha
S
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001369:Axons / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000378:metabolism; D009812:Odorants; D009830:Olfactory Bulb / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D012678:Sensation Disorders / Q000175:diagnosis* / Q000209:etiology; D012903:Smell / Q000502:physiology*; D013268:Stimulation, Chemical
D008345:Manganese