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Experimental models for the investigation of brain ischemia

Konstantin-Alexander Hossmann
DOI: http://dx.doi.org/10.1016/S0008-6363(98)00075-3 106-120 First published online: 1 July 1998
Keywords
  • Brain ischemia
  • Animal models
  • Stroke
  • Circulatory arrest
  • Resuscitation
  • Treatment

Time for primary review 28 days.

1 Introduction

More than any other organ of the body, brain integrity depends on the continuous blood supply of oxygen and glucose for covering the energy demands of the tissue. Cessation or severe reduction of blood flow results in almost instantaneous biochemical and functional deficits which become rapidly irreversible unless blood flow is promptly restored. The ischemia time that is tolerated by the brain depends, among others, on the density of ischemia, the tissue concentration of primary and secondary energy stores and the rate of energy consumption which, in turn, depends on the temperature, the degree of functional activity and the absence or presence of anesthetics and other drugs. There is also a major difference between the ischemic vulnerability of different regions of the brain. As an example, the CA1 sector of hippocampus may suffer irreversible injury after ischemia of as short as 5 min [94]whereas other nerve cell populations survive normothermic cerebrocirculatory arrest of as long as 1 h [77].

The pathophysiology of cerebral ischemia is further complicated by the fact that the severity of cell injury is modulated by numerous indirect or secondary consequences of the primary ischemic impact. Recirculation disturbances, stress responses, peroxidative changes, or the activation of genomic responses are only few examples of the large number of hemodynamic and molecular responses which determine the final outcome [153, 97]. The interpretation of experimental data of cerebral ischemia, therefore, requires intimate knowledge of the models and conditions under which the data have been collected. The number and diversity of such models, has become very large over the years because researchers have sought in vain for the ideal approach to study ischemic injury and its therapeutic reversal. Such an ideal model should be relevant to the clinical situation, it should be …

* Corresponding author. Tel.: +49 (221) 4726 211; Fax: +49 (221) 4726 325; E-mail: hossmann@mpin-koeln.mpg.de