Cumulative effect of repeated ischemia on brain edema in the gerbil. Biochemical and physiological correlates of repeated ischemic insults.
Using a bilateral carotid artery occlusion model in the gerbil, we evaluated the cumulative effect of repeated ischemic insults on various physiological and biochemical parameters in brain. The most striking consequence of repeated occlusions is a profound, delayed increase in brain edema between 6- and 24-hr recirculation, after a series of three 5-min occlusions carried out at 1-hr intervals. This increment in brain water is accompanied by morphological evidence of compressed capillaries with increased filling of larger vessels, consistent with impaired microcirculation even though total blood flow and total vascular volume return toward control levels. The effect on edema is most severe when occlusions are repeated during the period of postischemic hypoperfusion, although the mechanisms responsible for this effect remain to be determined. Histograms of cerebral cortical oxygen tension show a shift toward progressively lower values during the recirculation interval after each occlusion, suggesting that secondary hypoxia accompanying hypoperfusion may worsen the impact of successive ischemic intervals. Although levels of PCr and ATP indicate adequate recovery of energy metabolism between occlusions, slight elevations of brain lactate persist, consistent with continued hypoxia. Under the conditions employed in these studies, repeated occlusions give rise to progressively more prolonged deficits in brain protein synthesis activity, which may thus provide a useful index of the severity of the accumulated ischemic insult. Continued studies using this well-defined model should provide further insight into the pathophysiology of ischemic brain edema.
Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
T S
TS
Nowak
S
S
Tomida
R
R
Pluta
S
S
Xu
M
M
Kozuka
K
K
Vass
H G
HG
Wagner
I
I
Klatzo
D000818:Animals; D001810:Blood Volume; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D005260:Female; D005849:Gerbillinae; D008297:Male; D008833:Microcirculation; D009419:Nerve Tissue Proteins / Q000032:analysis; D010100:Oxygen / Q000032:analysis; D012008:Recurrence; D015424:Reperfusion
D009419:Nerve Tissue Proteins; D010100:Oxygen