Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats.
In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.
Tomimatsu
Takuji
T
Department of Obstetrics and Gynecology, Faculty of Medicine, Osaka University School of Medicine, 2-2, Yamada-oka, Suita, Osaka, Japan. tomimatu@gyne.med.osaka-u.ac.jp
Fukuda
Hirotugu
H
Endoh
Masayuki
M
Mu
Junwu
J
Watanabe
Noriyoshi
N
Kohzuki
Masatomo
M
Fujii
Eriko
E
Kanzaki
Toru
T
Oshima
Kazuo
K
Doi
Katsumi
K
Kubo
Takeshi
T
Murata
Yuji
Y
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001933:Brain Stem / Q000473:pathology / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005247:Feeding Behavior; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology*; D009048:Motor Skills / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases