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Biomedical subjects

M L Rennels

Publications and source records attributed to M L Rennels.

At least 19 recordsLinked to original sources

Focal cerebral edema impedes convective fluid/tracer movement through paravascular pathways in cat brain.

Cerebral blood vessels are accompanied by longitudinal paravascular fluid pathways that communicate with the subarachnoid space. After infusion into the subarachnoid space, the tracer protein, HRP, distributes throughout the brain with such rapidity as to suggest that the paravascular fluid transport system serves to flush the entire brain parenchyma. However, it was found that the tracer is largely excluded from regions of experimental vasogenic brain edema as well as from remotely situated white matter in the cold-lesioned hemisphere. The results suggest that the persistence and spread of vasogenic edema may be related to an impairment or disruption of the normal paravascular fluid transport system of the brain.

Animals↗

Rapid solute transport throughout the brain via paravascular fluid pathways.

Solutes in CSF have rapid access to ECS throughout the CNS (within 5-10 min). This occurs by solute/fluid influx through PVS around penetrating arteries, followed by longitudinal spread along the BL of capillaries to reach venules and veins. These paravascular pathways can be demonstrated light-microscopically by infusion of the tracer protein, HRP, into SAS and the subsequent localization of this probe molecule in brain sections using the sensitive histochemical method based on TMB. This unidirectional tracer/fluid movement along the intraparenchymal vascular network, with accompanying spread into the cerebral interstitium, appears to be facilitated by the pulsation of penetrating arterioles within their PVS with each cardiac contraction.

Animals↗

Marketing continuing education: a staff process.

State institutions of higher education are continually challenged to efficiently and effectively maximize every dollar spent. One means of realizing this goal is the development of an overall strategy to improve the marketing of continuing education programs. Because limited funds precluded hiring an individual to oversee marketing activities, one continuing education operation formed a steering committee of interested staff members to coordinate and expand its marketing efforts. This paper describes the evolution of staff involvement in an ongoing marketing process at a multidisciplinary center for continuing education and identifies some of the benefits of that involvement.

Academic Medical Centers↗

Evidence for a 'paravascular' fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space.

The protein tracer, horseradish peroxidase (HRP), was infused into the lateral cerebral ventricles or subarachnoid space of anesthetized cats and dogs after insertion of a cisternal cannula to permit drainage of cerebrospinal fluid (CSF) and tracer solution. The intracerebral distribution of the tracer was then determined by light microscopy of serial brain sections after postinfusion intervals of 4 min-2 h. For the localization of HRP, sections were incubated with diaminobenzidine (DAB) or the much more sensitive chromogen, tetramethylbenzidine (TMB). The TMB reaction showed a consistent 'paravascular' distribution of tracer reaction product, within the perivascular spaces (PVS) around large penetrating vessels and in the basal laminae around capillaries, far beyond the termination of the PVS. After infusion of HRP over 4 min, arterioles were surrounded by the tracer, but capillaries and venules were usually less densely demarcated; by 6 min, however, the intraparenchymal microvasculature was outlined in toto throughout the forebrain and brainstem. Electron microscopy of sections incubated in DAB after 10 or 20 min HRP circulation confirmed the paravascular location of the reaction product, which was also dispersed throughout the extracellular spaces (ECS) of the adjacent parenchyma. Our results demonstrate that solutes in the CSF have access to the ECS throughout the neuraxis within minutes via fluid pathways paralleling the intraparenchymal vasculature. The rapid paravascular influx of HRP could be prevented by stopping or diminishing the pulsations of the cerebral arteries by aortic occlusion or by partial ligation of the brachiocephalic artery. The exchange of solutes between the CSF and the cerebral ECS has generally been attributed to diffusion, however, HRP enters the neuraxis along the intraparenchymal microvasculature far more rapidly than can be explained on this basis. This apparent convective tracer influx may be facilitated by transmission of the pulsations of the cerebral arteries to the microvasculature. We postulate that a fluid circulation through the CNS occurs via paravascular pathways.

Anesthesia, General↗

A method for microscopic studies of cerebral angioarchitecture and vascular-parenchymal relationships, based on the demonstration of 'paravascular' fluid pathways in the mammalian central nervous system.

A new method is described for morphological studies of blood vessels and related cellular elements in the mammalian central nervous system (CNS). The tracer protein, horseradish peroxidase (HRP), in solution, is infused intraventricularly or intracisternally in anesthetized animals over 5-10 min. During this period, HRP in the subarachnoid space enters the perivascular spaces around penetrating arterioles and rapidly permeates the gliovascular basal laminae surrounding capillaries. After fixation by intravascular perfusion of aldehydes, brain sections are incubated with the highly sensitive chromogen, tetramethylbenzidine. Intraparenchymal blood vessels throughout the CNS are vividly demonstrated for light microscopy by HRP reaction product in their perivascular spaces or basal laminae. Correlative ultrastructural investigations of specific blood vessels and related parenchymal elements can be conducted using adjacent sections.

Animals↗

Innervation of capillaries by local neurons in the cat hypothalamus: a light microscopic study with horseradish peroxidase.

The protein tracer horseradish peroxidase (HRP) has been used in an attempt to define the cell bodies of origin of "nonadrenergic" varicose axons which terminate on the walls of hypothalamic capillaries. Capillaries in this region are also known to receive direct axonal contacts from adrenergic neurons in the pontine locus ceruleus. Solutions of HRP were infused into the lateral ventricles of adult cats of either sex and permitted to circulate in the cerebrospinal fluid spaces for 10 min, 20 min, or 2 h. During these periods HRP entered the perivascular spaces around penetrating arterioles and spread into the surrounding extracellular spaces of the hypothalamus. Certain neurons in the periarteriolar neuropil were consistently labeled by the tracer after all three circulation periods. These cells, including all of their processes, could be visualized in detail. Most neurons, by contrast, did not accumulate HRP. The axons of some tracer-filled neurons terminated on the walls of capillaries in the immediate vicinity of the penetrating arteriole. The arrangement and distribution of these cells suggest that they may provide a substrate for local neural influences on the hypothalamic microcirculation.

Animals↗

Spinal cord injury. The role of vascular damage in the pathogenesis of central hemorrhagic necrosis.

We postulated that damage to the endothelial lining of the spinal cord vasculature is a major factor in the pathogenesis of the characteristic lesion of the spinal cord (progressive, central, hemorrhage necrosis) that occurs after acute trauma. Endothelial damage may occur as a result of primary injury to the vessels or after arterial spasm. This damageresults in deposition of platelets and formation of thrombi on the exposed subendothelial tissues and embolization of such thrombi to smaller vessels of the spinal cord parenchyma.

Animals↗

Ultrastructure of pericytes in mouse heart.

The pericytes of mouse myocardium are extensively branched cells that form an incomplete layer around the endothelium of capillaries and postcapillary venules. The membranes of pericytes and endothelial cells are connected by specialized junctions. Microtubules, intermediate (10-nm) filaments and microfilaments are oriented within circumferentially-arranged cytoplasmic processes of pericytes so as partially to encircle the endothelial cylinder. The intracellular organization of these myocardial pericytes suggests that they are smooth muscle-like cells which may be capable of influencing microvascular dynamics in the heart.

Animals↗

Innervation of myocardial microcirculation; terminal autonomic axons associated with capillaries and postcapillary venules in mouse heart.

Efferent terminal axons are associated with numerous capillaries and postcapillary venules in both the atria and ventricles of mouse heart. These axons possess ultrastructural characteristics which are typical of peripheral autonomic fibers in other tissues. Many are found near pericytes, in a relationship closely resembling that between terminal axons and smooth muscle cells of larger vessels. To demonstrate adrenergic terminals, mice were pretreated with 5- or 6-hydroxydopamine; examination of these animals' hearts revealed that both adrenergic and cholinergic axons terminate near pericytes and endothelial cells. The results of this study are consistent with the view that there may be a functional innervation of capillaries and postcapillary venules of the mouse heart.

Adrenergic Fibers↗

Endothelial cell damage by temporary arterial occlusion with surgical clips. Study of the clip site by scanning and transmission electron microscopy.

The effects of temporary vascular occlusion with surgical clips on the underlying endothelial lining were studied with scanning (SEM) and transmission (TEM) electron microscopy. Twenty-five rabbits were anesthetized and both common carotid arteries exposed. A Heifetz clip was used to occlude the right carotid artery for 5, 15, and 30 minutes, and 2 hours in five animals each. The clips were removed and the vessels immediately perfused with glutaraldehyde. In five remaining animals, the right carotid arteries were occluded for 30 minutes followed by removal of the clip and resumption of blood flow for 30 minutes prior to fixation. Combined SEM and TEM examination of the endothelium of compressed segments revealed "craters" and "balloons", blebs and vacuoles, swollen mitochondria, dilated granular endoplasmic reticulum, and subendothelial edema. There were also areas of endothelial cell flattening, discontinuity, and desquamation exposing the subendothelial tissues. Following restoration of flow, platelets and fibrin were found adherent to altered endothelial cells and to exposed subendothelial tissues. Endothelial craters and balloons were also found distal and, significantly less frequently, proximal to the site of occlusion. It is suggested that antiplatelet aggregating agents may prove beneficial for the prevention of thrombus formation at the site of the clip as well as craters and balloons distal to the clip following procedures requiring temporary vascular occlusion.

Animals↗

Ischemic carotid endothelium. Transmission electron microscopic studies.

The endothelium of monkey and rabbit common carotid arteries subjected to ischemia was examined by transmission electron microscopy (TEM). The right carotid artery of 24 rhesus monkeys was occluded by proximal and distal placement of removable surgical clips for periods ranging from five minutes to four hours. A single clip was used to occlude the right carotid artery of 15 rabbits for periods ranging from 5 to 30 minutes. With TEM, numerous blebs, intracytoplasmic vacuoles, membranous whorls, and pseudopodia were found in the endothelium of arterial segments subjected to ischemia by double or single clipping for as little as five minutes. Following occlusion of one hour or longer, disruption of interendothelial junctions was also noted. These TEM findings were compared with earlier TEM studies of the response of endothelium to other injurious stimuli and with previous scanning electron microscopic studies in which the same ischemic models were utilized.

Animals↗

Ischemic carotid endothelium. Scanning electron microscopical studies.

The normal luminal surface and the effect of ischemia on the endothelium of the common carotid arteries of rhesus monkeys were examined by scanning electron microscopy. Clamps were placed proximally and distally on the right common carotid arteries, totally occluding the vessels for periods ranging from five minutes to four hours. The clamps were then removed and fixation carried out by intravascular perfusion. The contralateral sham-operated carotids, as well as those from unoperated animals were used as control specimens. The most obvious effect of ischemia was the appearance of conical, crater-like defects in the cytoplasm of endothelial cells. Such "craters" were observed following as little as 15 minutes of ischemia, were much less frequent in sham-operated vessels, and were not seen in the unoperated control specimens.

Animals↗