case western reserve university





Ita Kaiserman-Abramof, Ph.D.

Electron Microscopic Analysis of Functional Adaptations to Metabolic Stress in Brain Tissues

The primary interest of this laboratory is to closely assess and substantiate, on an ultrastructural level, the tissue responses to pathological changes resulting from stroke and hypoxia in brain. Cytotoxic edema causes metabolic and vascular failure and it has detectable structural characteristics which can be observed, analyzed, and reconstructed at an ultrastructural level. Two of the parameters which are likely to be sensitive to metabolic and vascular failure are endothelial cells and astrocytes, especially those closer to capillaries.

The central nervous system sequelae of cardiac arrest and resuscitation can be understood as two distinct phenomena. The first is the acute dysfunction or death of CNS neurons which result in cardiovascular and respiratory collapse leading to death of the organism. The acute phase can limit resuscitation from longer arrest and can also occur up to three days after resuscitation leading to secondary ischemic death. This phenomenon is most likely occurring through metabolic and functional failure of the brainstem, since the ischemic pressor response and apnea are known to be mediated by the ventral medulla. The second phenomenon is that of selective delayed neuronal degeneration. Some event triggered during the ischemia, and set into motion during the first few hours after resuscitation, results 3 or 4 days later in selective neuronal degeneration typified by the CA1 neurons of the hippocampus. Electron micrographs from rats perfused 5 minutes after resuscitation from 10 minutes of cardiac arrest show that the hippocampus capillaries exhibit swelling of pericapillary astrocytes and endothelial cells. However, neurons from CA1 hippocampal region are indistinguishable from control neurons with intact mitochondria and no swelling. In addition, the capillaries from the brainstem exhibit damage to the endothelial cells in the form of blebbing, but no swelling of the pericapillary astrocytes.


Selected References:

LaManna JC, JK Griffith, BR Cordisco, HE Bell, C-W Lin, S Pundik, and WD Lust: Rapid recovery of rat brain intracellular pH after cardiac arrest and resuscitation. Brain Res 687:175-181 (1995).


LaManna JC: Hypoxia/Ischemia and the pH Paradox. In: "Oxygen Transport to Tissue XVII," Ince C et al.., eds., Plenum Press, New York, pp. 283-292 (1996).


Hoxworth JM, K Xu, Y Zhou, WD Lust, and JC LaManna: Similar metabolic recovery of acute and chronic hyperglycemic rat brains following cardiac arrest and resuscitation. J Cereb Blood Flow Metab 17(Suppl 1):S360(1997).(Abs)


Stewart PA, H Isaacs, JC LaManna, and SI Harik: Ultrastructural concomitants of hypoxia-induced angiogenesis. Acta Neuropathol 93:579-584 (1997).

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