Induced cerebral hypothermia reduces post-hypoxic loss of phenotypic striatal neurons in preterm fetal sheep.
Perinatal hypoxic-ischemic injury of the basal ganglia is a significant cause of disability in premature infants. Prolonged, moderate cerebral hypothermia has been shown to be neuroprotective after experimental hypoxia-ischemia; however, it has not been tested in the preterm brain. We therefore examined the effects of severe hypoxia and the potential neuroprotective effects of delayed hypothermia on phenotypic striatal neurons. Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (fetal extradural temperature reduced from 39.4+/-0.3 degrees C to 29.5+/-2.6 degrees C) from 90 min to 70 h after the end of occlusion. Hypothermia was associated with a significant overall reduction in striatal neuronal loss compared with normothermia-occlusion fetuses (mean+/-SEM, 5.5+/-1.2% vs. 38.1+/-6.5%, P<0.01). Immunohistochemical studies showed that occlusion resulted in a significant loss of calbindin-28 kd, glutamic acid decarboxylase isoform 67 and neuronal nitric oxide synthase-immunopositive neurons (n=7, P<0.05), but not choline acetyltransferase-positive neurons, compared with sham controls (n=7). Hypothermia (n=7) significantly reduced the loss of calbindin-28 kd and neuronal nitric oxide synthase, but not glutamic acid decarboxylase-immunopositive neurons. In conclusion, delayed, prolonged moderate head cooling was associated with selective protection of particular phenotypic striatal projection neurons after severe hypoxia in the preterm fetus. These findings suggest that head cooling may help reduce basal ganglia injury in some premature babies.
George
S
S
Department of Physiology, Faculty of Medicine and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Scotter
J
J
Dean
J M
JM
Bennet
L
L
Waldvogel
H J
HJ
Guan
J
J
Faull
R L M
RL
Gunn
A J
AJ
D000818:Animals; D001238:Asphyxia Neonatorum / Q000503:physiopathology / Q000628:therapy*; D001831:Body Temperature / Q000502:physiology; D020520:Brain Infarction / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D064026:Calbindins; D016923:Cell Death / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D002534:Hypoxia, Brain / Q000503:physiopathology / Q000628:therapy*; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012756:Sheep; D016896:Treatment Outcome
D064026:Calbindins; D007527:Isoenzymes; D064030:S100 Calcium Binding Protein G; D052248:Nitric Oxide Synthase Type I; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1