Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH.
 ...
PMID:Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. 1 21

Experimental occlusion of the middle cerebral artery and the reduction of cerebral blood flow (CBF) below 15 ml/100 gm/per minute cause failure of the somatosensory evoked response and lethargy of cortical neurones. Increase of CBF to normal value normalises the bioelectrical activity within the "penumbra"--the zone surrounding the necrotic area. In this "risk zone" neurones can survive only a few hours. So the penumbra is a "therapeutic window" in which therapy can save some neurones from death. However, if decrease of CBF is continued, numerous cells within the penumbra gradually die. The phenomenon of the penumbra, based on experiments, was applied to human ischaemic stroke; however great differences between experimental and human brain ischaemia do exist. The human course of disease and the size of necrotic lesion depend on numerous additional factors. The three very important critical values of CBF which decrease in human brain ischaemia are difficult to examine. New imaging methods play a great diagnostic role in searching for the penumbra, but their diagnostic possibilities and results are limited. In the short-time duration of the therapeutic window both CT and MRI often do not indicate ischaemic lesion. So, it is not known whether the penumbra is present or not. Conclusive estimation of MRI diffusion-weighted imaging and perfusion-imaging and of their coefficient is impossible to obtain in the time exceeding the "therapeutic window'" Numerous additional various diseases and compensatory vascular mechanisms influence the necrotic zone in human focal ischaemia. Probably for this reason a difficulty in the estimation of the penumbra in human is observed. So, it seems that the penumbra--the therapeutic window or risk zone--in human probably occurs only in some cases. It may be one of numerous reasons for the limited effectiveness of ischaemic stroke therapy. It is not known when the penumbra is overspread with oedema, which always appears to a greater or a lesser degree. Maybe the efforts of experimental investigators, physicians and pharmacologists should also be taken into consideration to find drugs decreasing oedema and BBB permeability.
 ...
PMID:Experimental and human ischaemia: is the penumbra present in human ischaemic stroke? 1257 78