Global cerebral ischemia

Under physiologic conditions, the balance of membrane lipid metabolism, particularly that of arachidonoyl and docosahexaenoyl chains, favors a very small and tightly controlled cellular pool of free arachidonic acid (AA, 20 4n-3) and docosahexaenoic acid (DHA, 22 6n-3), but levels increase very rapidly upon cell activation, cerebral ischemia, seizures and other types of brain trauma [1, 2], Other free fatty acids (FFAs) in addition to AA, released during cell activation and the initial stages of focal and global cerebral ischemia, are stearic acid (18 0), palmitic acid (16 0) and oleic acid (18 1). 

Jin K, Mao XO, Eshoo MW, Nagayama T, Minami M, et al. 2001. Microarray analysis of hippocampal gene expression in global cerebral ischemia. Ann Neurol 50 93. 

In Section 1.1.1, L-deprenyl (2) was discussed as a potent selective MAO B inhibitor. Its p-fluoro analogue, fludeprenyl (7), was shown to retain the irreversible and selective inhibitory effects of its parent compound, with similar potency in vitro in rat tissue and in vivo in mice [33]. Both compounds have also been reported to have similar protective actions against transient global cerebral ischemia in gerbils. With L-deprenyl (2), these effects occurred at doses below those which inhibit MAO B, while the effects of the p-fluoro analogue 7 occurred only at doses that also inhibit MAO B activity [33b,34]. 

Grotta J. C., Picone C. M., Ostrow P. T., Strong R. A., Earls R. M., Yao L. P., Rhoades H. M., and Dedman J. R. (1990). CGS-19755, a competitive NMDA receptor antagonist, reduces calcium-calmodulin binding and improves outcome after global cerebral ischemia. Ann. Neurol. 27 612-619. 

Oxidative neuronal damage also contributes to delayed neuronal death after global cerebral ischemia as demonstrated by studies in humans (Love et al. 1998, 1999). 

We present here the first comprehensive analysis of the distribution, quantity, and phenotype of de novo-generated cells in several regions of adult primate brain after transient global cerebral ischemia. 

We performed transient global cerebral ischemia on adult macaque monkeys by reversibly stopping blood flow to the brain. We labeled de novo-generated cells in postischemic animals as well as in sham-operated controls by infusing the DNA synthesis indicator BrdU, and subsequently investigated the distribution and phenotype of BrdU-labeled cells in several telencephalic regions at various time-points after ischemia. 

Tonchev AB, Yamashima T, Sawamoto K, Okano H (2005) Enhanced proliferation of progenitor cells in the subventricular zone and limited neuronal production in the striatum and neocortex of adult macaque monkeys after global cerebral ischemia. J Neurosci Res 81 776-788... 

Distribution and Phenotype of Proliferating Cells in the Forebrain of Adult Macaque Monkeys After Transient Global Cerebral Ischemia... 

Martin, L. J., Al-Abdulla, N. A., Brambrink, A. M., Kirsch, J. R., Sieber, F. E., and Portera-Cailliau, C. (1998). Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation A perspective on the contributions of apoptosis and necrosis. Brain Res. Bull. 46, 281-309. 

Li, H., Colboume, F., Sun, P., Zhao, Z., Buchan, A. M., and Iadecola, C. (2000). Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats. Stroke 31, 176—182. 

The insight into the dynamic nature of ischemic brain lesions has raised growing attention over the past few years. Distinct temporal and spatial patterns of lesion evolution have been described for two types of cerebral ischemia that differ in many pathophysiological aspects namely conditions of focal and global cerebral ischemia. 

In 1987, however, a study by Busto et al. (5) showed that small decreases in brain temperature (as little as 2-5°C below normal brain temperature) conferred a marked protective effect against experimental global cerebral ischemia. This finding, as well as subsequent animal studies that modeled neurodegenerative diseases and CNS injury, led to a resurgence of interest in mild hypothermia as a method of cerebral protection. 

Chopp M., Knight R., Tidwell C. D., Helpern J. A., Brown E., and Welch K. M. (1989) The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat comparison to normothermia and hyperthermia. J. Cereb. Blood Flow Metab. 9, 141-148. 

Horn M., Schlote W., and Henrich H. A. (1991) Global cerebral ischemia and subsequent selective hypothermia. A neuiopathological andmorphometrical study on ischemic neuronal damage in cat. Acta Neuropathol. (Berl.) 81,443-449. 

Green E. J., Dietrich W. D., van Dijk F., et al. (1992) Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats. Brain Res. 580, 197-204. 

ChoppM., Welch K.M., TidwellC.D., Knight R., andHelpemJ. A. (1988) Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats. Stroke 19, 1521-1525. 

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