Biomedical subjects

K U Frerichs

Publications and source records attributed to K U Frerichs.

22 records · Page 2Linked to original sources

PubMed1990

Increased cerebral lactate output to cerebral venous blood after forebrain ischemia in rats.

Increased cerebral lactate levels are a well-known aspect of the sequelae of the metabolic derangements that follow cerebral ischemia. A new technique has recently become available to sample cerebral venous blood from the superior sagittal sinus on a long-term basis in conscious rats. We report the applicability of this method to assess serial biochemical responses to brain injury. Serum samples were obtained from the superior sagittal sinus, the common carotid artery, and the external jugular vein of nine anesthetized rats before and up to 7 days after 10 minutes of forebrain ischemia was produced by carotid occlusion and hypovolemic hypotension (mean arterial blood pressure 50 +/- 4 mm Hg). The cerebral venous-arterial difference in serum lactate concentration was increased for up to 3 hours after ischemia, while there was no significant change in the difference in serum lactate concentrations in the common carotid artery and the external jugular vein. This indicates an elevated output of lactate from brain tissue to blood, detectable only in the superior sagittal sinus, which underlines the usefulness of the technique. We observed a persistent elevation in brain lactate production after virtually complete recovery from the acute insult.

Animals↗

PubMed1990

Platelet-activating factor and progressive brain damage following focal brain injury.

The effects of a platelet-activating factor (PAF) antagonist on brain edema, cortical microcirculation, blood-brain barrier (BBB) disruption, and neuronal death following focal brain injury are reported. A neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to induce highly reproducible focal cortical lesions in anesthetized rats. Secondary brain damage in this model was characterized by progressive cortical hypoperfusion, edema, and BBB disruption in the vicinity of the hemispheroid lesion occurring acutely after injury. The histopathological evolution was followed for up to 4 days. Neuronal damage in the cortex and the hippocampus (CA-1) was assessed quantitatively, revealing secondary and progressive loss of neuronal tissue within the first 24 hours following injury. Pretreatment with the PAF antagonist BN 50739 ameliorated the severe hypoperfusion in 12 rats (increasing local cerebral blood flow from a mean +/- standard error of the mean of 40.5% +/- 8.3% to 80.2% +/- 7.8%, p less than 0.01) and reduced edema by 70% in 10 rats (p less than 0.05) acutely after injury. The PAF antagonist also reduced the progression of neuronal damage in the cortex and the CA-1 hippocampal neurons (decrease of neuronal death from 88.0% +/- 3.9% to 49.8% +/- 4.2% at 24 hours in the cortex and from 40.2 +/- 5.0% to 13.2% +/- 2.1% in the hippocampus in 30 rats; p less than 0.05). This study provides evidence to support progressive brain damage following focal brain injury, associated with secondary loss of neuronal cells. In this latter process, PAF antagonists may provide significant therapeutic protection in arresting secondary brain damage following cerebral ischemia and neurological trauma.

Animals↗

PubMed1990

Platelet-activating factor--key mediator in neuroinjury?

A growing body of evidence supports the hypothesis that platelet-activating factor (PAF) may be a key mediator in neuroinjury. PAF, originally isolated from stimulated basophils, can be produced by a variety of cells, such as polymorphonuclear leukocytes (PMNLs), platelets, monocytes, macrophages, and endothelial cells and has been suggested as a mediator of inflammation, platelet and neutrophil activation, plasma extravasation, and anaphylactic shock. Enhanced phospholipid metabolism in the ischemic penumbral zone has been reported and provides opportunity for production of PAF. A possible involvement of this lipid mediator in processes associated with cerebral ischemia and neurotrauma has been suggested by an increasing number of reports. PAF exerts cytotoxic effects on neuronal cells, causes vasoconstriction, and increases the blood-brain barrier permeability. Beneficial effects of PAF antagonists have been shown in various models of cerebral ischemia: pre- as well as postischemic application of the PAF antagonist resulted in reduction of edema and improved neurological outcome and improved cerebral microcirculation. These effects were correlated with improved neuronal survival and reduced accumulation of PMNLs, supporting a link and positive feedback between PAF and PMNLs in these processes. Since PAF appears to be uniquely involved in various pathophysiological events, it may function as a key mediator in ischemic and traumatic neuroinjury. The current review summarizes the current understanding of the function and biochemistry of PAF with respect to CNS physiology and pathology.

Brain↗

PubMed1989

Long-term sampling of cerebral venous blood in conscious rats.

The mechanisms of secondary brain damage following cerebral ischemia or CNS trauma are still unknown. A variety of mediators, released by the injured brain, are held to be responsible for delayed neuronal cell damage. No technique is available yet for repeated sampling of cerebral venous blood (CVB) on a long-term basis, which allows to assess the neurobiochemical responses to brain injury chronically in conscious laboratory animals. This is a report on the establishment of a method to sample CVB from the superior sagittal sinus (SSS) for at least 7 days in conscious freely moving rats. The torcular was exposed for implantation of a catheter into the caudal SSS. Patency was preserved by perfusion with a nonsystemic dose of heparin by an Alzet osmotic pump and verified daily by aspirating of 0.5 ml CVB for blood analysis. No neuropathology was seen in histological examination. The rats appeared comfortable and without distress, and the transient weight loss was rapidly regained. The present model provides the opportunity to evaluate acute or chronic neurobiochemical responses to stroke, CNS trauma, or any other typ of brain injury in the conscious rat.

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