Brain global ischemia

Energy metabolites in gerbil brain Global Ischemia... 

Globus MY, Busto R, Lin B, Schnippering H, Ginsberg MD. Detection of free radical activity during transient global ischemia and recirculation effects of intraischemic brain temperature modulation. J Neurochem 1995 65 1250-1256. 

Shutenko Z, Henry Y, Pinard E, Seylaz J, Potier P, Berthet F. 1999. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol 57 199-208. 

Endoh, M., Pulsinelli, W. A., and Wagner, J. A. (1994). Transient global ischemia induces dynamic changes in the expression of bFGF and FGF receptor. Mol. Brain Res. 22, 76-88. 

Dijkhuizen RM, de Graaf RA, Tulleken KA, Nicolay K (1999) Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain. J Cereb Blood Flow Metab 19 341-349... 

Hossmann KA (1997) Reperfusion of the brain after global ischemia hemodynamic disturbances. Shock 8 95-101 Hossmann K-A (1987) Pathophysiology of cerebral infarction. In Vinken PJ, Bruyn GW, Klawans HL (eds) Handbook of clinical neurology. Elsevier, Amsterdam, pp 107-153 Hossmann K-A (1991) Animal models of cerebral ischemia. 1. 

Fig. 1. (previouspage) Paraffin-embedded coronal brain sections stained with hematoxylin and eosin from normothermic—ischemic (a, b) and hypothermic-ischemic (c, d) rats, (a) Two months after 12.5 min of normothermic (37°C) global ischemia, severe necrosis of CA1 hippocampus is evident (xl20). 

Ten years ago, it was observed in a model of 5-min global ischemia in gerbils that the expected severe hippocampal neuronal loss could be markedly attenuated by prolonging the period of halothane anesthesia, which blunted the mild postischemic hyperthermia (approx 1,5°C) that would otherwise occur (55). This effect was not specific to halothane but rather could be duplicated by warming the head by a similar amount in its absence. This study established the marked sensitivity of the postischemic brain to even mild hyperthermia. 

Postischemic oxygen radical production is also accentuated by hyperthermia. Microdialysis studies sampling the brain s extracellular fluid for a signal of hydroxyl radical production have revealed two- to threefold elevations after normothermic global ischemia, but four- to... 

Pazos A. J., Green E. J., Busto R., et al. (1999) Effects of combined postischemic hypothermia and delayed A-tert-butyl-alpha-pheylnitrone (PBN) administration on histopathological and behavioral deficits associated with transient global ischemia in rats. Brain Res. 846, 186-195. 

Based on experimental and clinical data, cerebral hypothermia appears to be a potent therapeutic approach to treating brain trauma. However, recent results from the Multicenter National Brain Injury Study Hypothermia (NABIS H) clinical trial appear to be disappointing, and more refinement of the clinical application of hypothermia is required (73). Additional clinical trials are now required to evaluate systematically the beneficial effects of clinical hypothermia in different populations of brain-injured patients. In addition, experimental data regarding the beneficial effects of combination therapy are required to evaluate whether hypothermia plus pharmacotherapy may provide a better outcome. Forexample, mildpostischemichypothermia(33-39°C) combined with the antiinflammatory cytokine IL-10 has recently been reported to produce long-term protection of the C Al hippocampus after transient global ischemia (74). Hypothermia or IL-10 treatment alone did not protect chronically. In contrast, Kline etal. (75) showed that acute systemic administration of IL-10 suppressed the beneficial effects of... 

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