Analysis of spatial and temporal protein expression in the cerebral cortex after ischemia-reperfusion injury.
OBJECTIVE
Hypoxia, or ischemia, is a common cause of neurological deficits in the elderly. This study elucidated the mechanisms underlying ischemia-induced brain injury that results in neurological sequelae.


METHODS
Cerebral ischemia was induced in male Sprague-Dawley rats by transient ligation of the left carotid artery followed by 60 min of hypoxia. A two-dimensional differential proteome analysis was performed using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to compare changes in protein expression on the lesioned side of the cortex relative to that on the contralateral side at 0, 6, and 24 h after ischemia.


RESULTS
The expressions of the following five proteins were up-regulated in the ipsilateral cortex at 24 h after ischemia-reperfusion injury compared to the contralateral (i.e., control) side: aconitase 2, neurotensin-related peptide, hypothetical protein XP-212759, 60-kDa heat-shock protein, and aldolase A. The expression of one protein, dynamin-1, was up-regulated only at the 6-h time point. The level of 78-kDa glucose-regulated protein precursor on the lesioned side of the cerebral cortex was found to be high initially, but then down-regulated by 24 h after the induction of ischemia-reperfusion injury. The expressions of several metabolic enzymes and translational factors were also perturbed soon after brain ischemia.


CONCLUSIONS
These findings provide insights into the mechanisms underlying the neurodegenerative events that occur following cerebral ischemia.
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Yuan-Hao
YH
Chen
Section of Neurosurgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC.
Yung-Hsiao
YH
Chiang
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Hsin-I
HI
Ma
cerebral ischemia; gerontology; neurodegenerative mechanisms; protein expression; proteomics; reperfusion injury