Cerebral global

Cerebral global transient ischaemia in rats induced a rise in cNOS activity from 62.0 6.1 to 133.3113.3 pmol/min x mg protein and cGMP levels from 459.3149.6 to 1974.11132.1 fmol/mg protein (FernAndez etal. 1997). Pre-treatment with 10 mg desmethyl tirilazad/kg intraperitoneally abolished these increases. 

Desmethyl tirilazad reduced brain nitric oxide synthase activity and cyclic guanosine monophosphate during cerebral global ischaemia in rats (Fernandez et al. 1997). 

Toung TJ, Hum PD, Traystman RJ, Bhardwaj A. Global brain water increases after experimental focal cerebral ischemia effect of hypertonic sahne. Crit Care Med 2002 30(3) 644-649. 

Linde, R., Schmalbruch, I. K., Paulson, O. B. etal. The Kety-Schmidt technique for repeated measurements of global cerebral blood flow and metabolism in the conscious rat. Acta Physiol. Scand. 165 395-401,1999. 

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). 

The initial neurological symptoms of hypoxia and hypoglycemia result from reduced synthesis of neurotransmitters rather than a global cerebral energy deficit 594... 

O Neill, M. J., Bond, A., Omstein, P. L., Ward, M. A., Hicks, C. A., Hoo, K., et al. (1998) Decahydroisoquinolines novel competitive AMPA/kainate antagonists with neuroprotec-tive effects in global cerebral ischaemia. Neuropharmacology 37,1211-1222. 

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. 

Unlike barbiturates, benzodiazepine derivatives administered orally lack a general anesthetic action cerebral activity is not globally inhibited (respiratory paralysis is virtually impossible) and autonomic functions, such as blood pressure, heart rate, or body temperature, are unimpaired. Thus, benzodiazepines possess a therapeutic margin considerably wider than that of barbiturates. 

A global view of consciousness is that it is generated throughout the entire brain, as a result of synchronisation of relevant neural networks. Specific systems or regions—for example the cerebral cortex, brainstem reticular formation and thalamic nuclei—may be key anatomical integrators. Areas with the most widespread interconnections are pivotal, and on this basis the cortex and thalamus are more relevant than cerebellum and striatum for example. Frontal cortex for example connects with every other brain region, both in terms of input and output, with 80% of such connections accounted for by cortico-cortical connections. Thalamic intralaminar nuclei are, in conjunction with the reticular nucleus, reciprocally connected to all cortical areas. By contrast the cerebellum has very few output pathways and striatal-cortical input is (via the thalamus) confined to frontal lobe. 

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]. 

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