A uniform, predictable pattern of cellular abnormalities is seen after complete, irreversible ischemic injury to the central nervous system. This is in contrast to the heterogeneous, multifocal picture which characterizes incomplete ischemia. The range of abnormalities in neuronal soma after an arterial occlusion changes considerably as a function of time and site. There is no single pattern of neuronal alteration that can be ascribed exclusively to ischemia. Red neurons are a relatively late (about 18 h) indicator of ischemia and are seen only in areas where blood supply is marginal. In addition to depletion of high-energy-phosphate reserves, brain ischemia results in characteristic alterations of amino acid concentrations in the ischemic tissue. Glutamate, glutamine, and aspartate either decrease or remain constant while alanine increases. Proportional decreases in the former three amino acids may be explained by simple dilution due to edema. Increases in alanine relative to glutamate and aspartate may be utilized as a biochemical index of perfusion to various brain regions.
We describe a method for typing neurons into four progressive stages of ischemic deterioration based on visual characterization of the nucleus in terms of its optical contrast, delineation along the nuclear-cytoplasmic interface, and its shape. Difficulty in assessing nuclear shape required the introduction of an angularity comparator chart to improve the investigator's accuracy. Three investigators typed neurons obtained from normal, ischemic, and ischemicreperfused rat brains. Accuracy and reproducibility of the investigators' typing decisions with and without the angularity comparator charts were evaluated. The accuracy of subjective shape assessment was compared with objective digitizer measurements of the same. The angularity comparator charts reduced subjective shape classification error by two thirds, and group error (overall performance expressed by the coefficient of variance) decreased from 15.9% to 4.7% for Type I (normal cells), from 33.9% to 173% for Type II (cells with angular nuclei), from 15.5% to 14.1% for Type III (cells with smeared nuclei), and from 3.2% to 5.5% for Type IV (dead cells). Thus, Type I and IV neurons can be assessed at a higher reproducibility than the intermediate Types II and III. Our typing method can also be used to evaluate the effect of treatment regimes on ischemic neuronal damage. (Stroke 1990^1:299-304) T he last two or three decades have witnessed significant advances in our basic understanding of the pathophysiology of cerebrovascular ischemic disease. Fundamental mechanisms contributing to ischemic neuronal damage have been elucidated. The most secure strides in scientific progress have generally occurred in those fields insisting on strict quantification. Despite the advent of exciting technologic advances that permit in vivo imaging of metabolic derangements associated with brain ischemia, it is likely for the foreseeable future that light microscopy will remain the most practical, reliable, and definitive laboratory tool for assessing the degree of ischemic tissue damage. However, shortcomings do exist in the histologic assessment of ischemic brain damage. Experimental investigations of neuronal grading schemes to date, virtually without exception, have certain weaknesses in common. To our knowledge, no cell typing scheme has yet been examined critically or documented fully for user reliability, accuracy, and internal redundancy. Until Received June 7, 1989; accepted September 19, 1989. such an evaluation is performed, any proposed taxonomy of ischemic neuronal injury must be viewed as suspect and arbitrary. It is the burden of each research group using an ischemic grading scale to establish its scientific rationale and to prove the discriminative capabilities of its choices. A human observer perceives many distinct features of cellular pathology under oil-immersion light microscopy in l-^,m-thick plastic sections. Only a small fraction of these features are pertinent to ischemic cellular decay and can be detected at an acceptable level of confidence. These fe...
Summary: This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue Po 2 % was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum elec trodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the P0 2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 fLm of each of 19 electrode sites among seven rats was evaluated histologically. There was a posAn important controversy in brain ischemia re search is whether the time course of reperfusion after ischemia can influence the extent or degree of neuronal injury. It seems desirable to terminate the ischemic energy deficit and acidosis as quickly as possible. Some brain regions that develop multiple capillary occlusions during ischemia may not regain circulation ("no reflow") when the main feeding vessel is reopened unless hypertension with global hyperemia is induced. But such hyperemia may ag gravate postischemic edema. It has not been con clusively established, however, if the resulting edema contributes significantly to subsequent tis sue injury.Recent research has revealed at least three pro cesses that contribute to neuronal necrosis: opening
The objective of the present work was a theoretical evaluation of pial arterial pressures in normotensive rats and spontaneously hypertensive rats based on the geometry and topography of the pial arterial system as well as on various topological models of the vascular trees. Pial branches of the middle cerebral artery in the diameter range of 30-320 microns were selectively visualized by corrosion compound, and the diameter and length of vascular segments were measured. The vessels were classified into branching orders by the methods of Horsfield and Strahler. The steady-state pressure distribution in the pial arterial system was calculated assuming that the flow at the bifurcations was partitioned in proportion to a given power of the diameters of the daughter branches (diameter exponent). The maximum number of vascular segments along the longest branch varied between 16 and 33. The mean branching ratio was 4.14 +/- 0.23 (SD). The mean diameter of vessels classified into Strahler orders 1-5 were: 50 +/- 12, 71 +/- 19, 106 +/- 22, 168 +/- 22, and 191 +/- 7 microns, respectively. The calculated pressure drop in the pial trees of normotensive rats was approximately twice as large in proximal orders 3 and 4 than in distal orders 1 and 2. The mean pressure in arteries of order 1 ranged from 54.4 to 58.4 mm Hg in the normotensive rat (input pressure: 83 mm Hg), and from 77.2 to 89.0 mm Hg in the spontaneously hypertensive rat (input pressure: 110 mm Hg). The coefficient of variation of terminal pressures in vessels of order 1 increased linearly with the mean pressure drop in the system. The coefficient of variation in terminal pressure had a minimum as a function of the diameter exponent in case of each pial tree. At its minimum, it was higher in all spontaneously hypertensive rats (10.1-22.9%) than in any normotensive rats (6.0-8.5%). The corresponding diameter exponents were in most cases lower in the spontaneously hypertensive rat (1.3-2.5) than in the normotensive rat (2.5-3.0). Topologically consistent models of the pial arterial network predicted significantly less variation in intravascular pressures than was obtained by direct calculations. More idealized models suggested the dependence of coefficient of variation in terminal pressure on the total number of vascular segments contained by the tree. All models predicted the existence of the minimum of coefficient of variation in terminal pressure in function of the diameter exponent.(ABSTRACT TRUNCATED AT 400 WORDS)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.