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Biomedical subjects

K A Conger

Publications and source records attributed to K A Conger.

13 recordsLinked to original sources
PubMed1991

The contribution of reoxygenation to ischemic brain damage.

This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue PO2% was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum electrodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the PO2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 microns of each of 19 electrode sites among seven rats was evaluated histologically. There was a positive correlation between reoxygenation level and severity of neuronal damage. Perineuronal lucent halo formation, probably representing astrocyte foot process swelling, was negatively correlated with reoxygenation level. This study demonstrates that ischemic neuronal damage was aggravated by increased reoxygenation but that perineuronal swelling, as evidenced by halo formation, was somewhat ameliorated.

Animals↗
PubMed1990

Histologic assessment of neurons in rat models of cerebral ischemia.

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 ischemic-reperfused 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 17.3% 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.

Animals↗
PubMed1989

Classifying cells from light microscopic bit features by binary logic. Application to grade neuronal injury in cerebral ischemia.

Degradative cellular processes within neurons were analyzed and graded by a conceptually new approach that decoupled the process of subcellular feature analysis and grading, the latter being based on the severity of observed deterioration in subcellular features. Rather than evaluate the cell's histologic image in a panoramic manner, investigators were required to give simple yes-no decisions about the presence or absence of a specific pathologic feature (bit feature as opposed to panoramic analysis). Multiple elementary decisions create a binary representation of the cell image that can be easily handled and analyzed using computer techniques to generate all possible unique phenotypes of the scanned neuronal population. In the first application of this method, however, the number of possible phenotypes were reduced by imposed a priori logic on the separation scheme focusing on a single cellular structure (the nucleus) that was followed through the stages of structural decay. We experimentally validated four neuronal types of five theoretical possibilities when three nuclear bit features were used in typing. Grading of neuronal injury for groups of normal, ischemic, and ischemic and reperfused rats into two, three, and four categories are reported. The consistency at which the method can be implemented was assessed by calculating the mean and standard deviation of the reconciled typing decisions given by the four investigators. The group of the four investigators showed less than 2, 3, and 5% error when grading cells from control, ischemic, and ischemic-reperfused animals, respectively.

Animals↗
PubMed1988

Mathematical analysis of network topology in the cerebrocortical microvasculature.

The three-dimensional branching pattern of deep cerebrocortical capillary networks was reconstructed from histological sections. The distribution of blood flow in a mathematical model of the reconstructed network was calculated. The transit of red blood cells through the network was simulated by computer, and the total path length traveled by the cells was estimated. The results support both anatomical and hemodynamic heterogeneity of the cerebrocortical microvascular system.

Animals↗
PubMed1988

Computer-regulated constant pressure ischemia in the rat: the animal model.

A system permitting computer control of partial ischemia in the normotensive rat brain was developed. Right carotid cannulation and bilateral subclavian artery occlusion made the input of blood to the brain dependent solely on left carotid artery flow. Perfusion pressure was controlled by partial compression of this artery with a balloon. The system can produce a range of partial ischemic states maintaining perfusion pressures from 4 to 20 mm Hg. The adequacy of the servo-control system was evaluated in greater detail at requested perfusion pressures of 7 and 12 mm Hg in 14 male Sprague-Dawley rats (300-450 g). Experimentally obtained cerebral perfusion pressures of 6.84 (SD = 0.25, n = 7) and 11.72 (SD = 0.89, n = 7) mm Hg, respectively, demonstrate the efficacy of the system. CBFs were concurrently measured at four separate bilaterally symmetric anatomic sites (cortex, hippocampus, thalamus, and substantia nigra). Significant intra- and interhemispheric differences were found to exist, with regional flows monitored ipsilaterally to the carotid balloon exceeding those of the opposite hemisphere. In summary, this acute model of cerebral ischemia permits control of perfusion pressure over the entire critical partial ischemic range.

Animals↗
PubMed1988

The role of tissue acidosis in ischaemic tissue injury: the concept of the pH integral.

Cerebral cortical tissue pH was monitored with an extracellular glass electrode in 32 rats subjected to total global cerebral ischaemia produced by ligation of the basilar and carotid arteries with systemic hypotension for periods of 8 to 60 min. The totality of the ischaemia, and its duration were confirmed by monitoring with a brain tissue O2 electrode. Reperfusion was induced by hypertension and maintained thereafter to exclude delayed ischaemia during 3 h survival after which the rats were sacrificed by perfusion fixation. The severity of tissue pH change was varied by inducing hyperglycaemia in some of the rats. Quantitative counts were made of neurons demonstrating changes reflecting severe ischaemic injury within 500 microns of the electrode tip. For the criterion of an ischaemically injured neuron count greater than 20%, there appeared to be a threshold at about 30 min, and more than 0.8 units change in pH. For quantitative assessment of the ischaemic insult a more satisfactory index was found by combining both time and acidosis as the integral of the pH change during the period of ischaemia. This was found to have a strong correlation with the histologic changes. There was a less strong correlation between the acidosis during reperfusion and the histologic change. Comparing these results with those for 3 rats subjected to 215 min of ischaemia without reperfusion, it appears that most of the effect of acidosis in aggravating ischaemic injury takes place during the first hour of ischaemia with little further aggravation for longer periods.

Acidosis↗
PubMed1988

Patterns of EEG frequency content during experimental transient ischaemia in subhuman primates.

EEGs were recorded with depth electrodes in 8 monkeys undergoing transient middle cerebral artery ligation. Electrodes measured EEG, cerebral blood flow (CBF), and tissue oxygen simultaneously during and after occlusion. An EEG frequency analysis was performed. Electrode sites were examined microscopically, and infarction size, tissue vacuolization index, and neuronal morphology were described quantitatively. Serial neurological examinations were performed. Two patterns of EEG frequency change were delineated, dependent upon degree of ischaemia. Mild ischaemia, as indicated by less severe clinical deficits, higher CBF during occlusion, and minor pathological changes was associated with large increases in slow EEG activity and decreases in fast EEG activity during occlusion, with recovery of slow activities to baseline, but continued suppression of fast activities 24 h later. Severe ischaemia was associated with suppression of both fast and slow frequencies during occlusion, with slow activities returning to baseline and fast activities remaining suppressed 24 h later. The best quantitative EEG indicator of severity of ischaemia was suppression of slow wave activity during occlusion. The best EEG indicator that an ischaemic event had occurred 24 h previously was continued suppression of fast EEG activities. These data may be helpful in the design of EEG frequency analysis studies for monitoring the time course of human cerebral ischaemia and for retrospective diagnosis of transient ischaemic attacks (TIAs).

Animals↗
PubMed1987

Pressure distribution in the pial arterial system of rats based on morphometric data and mathematical models.

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)

Animals↗
PubMed1978

Neuronal ischemic injury: light microscopy, ultrastructure and biochemistry.

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.

Alanine↗
PubMed1978

The effect of aldehyde fixation on selected substrates for energy metabolism and amino acids in mouse brain.

The effect of aldehyde fixation on concentrations of low molecular weight constituents was determined by comparing amounts of selected intermediates in brains of mice exposed to aldehyde fixative solutions with those perfused with phosphate buffer solution alone. Aldehyde perfusion resulted in excellent preservation of cerebral cortex ultrastructure in the presence of dramatic declines in adenosine triphosphate, phosphocreatine, glucose and glucose-6-phosphate that occureed before exposure of the tissue to aldehyde fixatives. Decreases in hexose were accompanied by approximately a 4-fold increase in lactate and a 2-fold increase in pyruvate. Glycogen levels decreased by about 60% during the initial operative procedure but remained constant after aldehyde fixation. Glycogen content declined approximately 90% in tissues that were not treated with aldehyde. Concentrations of aspartate and glutamate changed only slightly during the initial period (1-5 min) and remained constant for at least 90 min in cerebral cortices fixed with aldehydes. Alanine levels increased in both fixed and unfixed tissue; however, this increase was much smaller in tissues exposed promptly to aldehydes. Total ninhydrin-positive material in perchloric acid extracts of brain decreased in mice exposed to aldehyde solutions but increased in tissues that were not. These results indicated that several amino acids may be measured reliably in tissues preserved for light and electron microscopy. In addition, determination of glutamate: alanine ratios in tissues perfused with aldehydes may provide an indication of the timing of fixation.

Aldehydes↗
PubMedDate not supplied

Innervation of brain intraparenchymal vessels in subhuman primates: ultrastructural observations.

Sympathetic innervation of intraparenchymal blood vessels in the basal ganglia was demonstrated by transmission electron microscopy in arteries, arterioles, and capillaries of the subhuman primate brain. Small arteries (40-120 micron) and some arterioles (12-40 micron) are innervated only at branching sites. However, arterioles occasionally may be innervated at points distal to their origin. Capillary innervation was very infrequently observed.

Animals↗