0000000000160993
AUTHOR
Ludwig Schürer
Effect of Torasemide — A New Cl--Transport Inhibitor on Glial Swelling by Lactacidosis and Glutamate
Cytotoxic brain edema, i.e. swelling of glial- and nerve cells is a common result of cerebral ischemia, brain trauma, metabolic disorders, and develops secondarily in vasogenic edema. During ischemia and severe head injury, brain tissue homeostasis is severely changed, and many parameters are simultaneously affected. To dissect and isolate the causal mechanisms leading to swelling of nerve- and glial cells, our laboratory has established an in vitro model [4, 5]. Thereby pathomechanisms can be studied in isolation without interference of epiphenomena taking place in damaged brain tissue under circumstances of cerebral ischemia or trauma. In previous studies the role of acidosis in cell swel…
Cerebral protection against ischemia by locomotor activity in gerbils. Underlying mechanisms.
Background and Purpose A previous communication of this laboratory demonstrated reduced mortality and neuronal damage by spontaneous locomotor activity preceding forebrain ischemia in Mongolian gerbils. The present experiments seek to elucidate potential mechanisms of protection by measurement of cerebral blood flow, cerebral tissue conductance as an indicator of ischemic cell swelling, and the cerebral release of eicosanoids. Methods Gerbils were maintained either in conventional cages (nonrunners) or with free access to running wheels (runners) for 2 weeks preceding 15 minutes of forebrain ischemia. During ischemia and 2.5 hours of reperfusion, cerebral tissue conductance was determined …
Electrical Impedance, ICP and Histology in Rats with Sagittal Sinus Occlusion
The diversity of clinical symptoms developing after thrombosis of the cerebral superior sagittal sinus is not well understood [2, 4], This is largely related to our ignorance of the underlying pathophysiology. An improvement in the pathophysiological understanding can be expected by experimental studies. Although animal models are available fot that purpose they are, however, in short supply. A few years ago, our laboratory in collaboration with the department of neurology at the University of Munich made another attempt to establish a reproducible experimental model for the induction of thrombosis of the superior sagittal sinus in rats. In the present studies this model has been used to ev…
Relationship of Cerebral Blood Flow Disturbances with Brain Oedema Formation
Brain oedema is an important factor which compromises maintenance of the cerebral blood flow. Conversely, primary blood flow disturbances are leading to brain oedema. The mechanisms underlying blood flow impairment by brain oedema are associated with an increased regional tissue pressure in proportion to the degree of water accumulation in the parenchyma. The release of vasoactive mediator compounds might be considered in addition. Primary disturbances of the cerebral blood flow, such as focal or global cerebral ischaemia are leading to an increased cerebral water content. A decrease of the cerebral blood flow to ca. 40% of normal or below has been found to result in the development of brai…
Swelling of glial cells in lactacidosis and by glutamate: significance of Cl(-)-transport.
Swelling of glial and nerve cells is characteristic of brain damage in cerebral ischemia or trauma. The therapeutical efficiency of inhibition of Cl(-)-transport by a novel antagonist, the diuretic torasemide, on cytotoxic swelling of glial cells from lactacidosis, or glutamate was analyzed. Lactacidosis and the interstitial accumulation of glutamate are hallmarks of the pathophysiological alterations in ischemic or traumatic brain tissue. C6 glioma cells harvested from culture and suspended in a physiological medium were either exposed to pH 6.2, or 5.0 by lactic acid, or exposed to 1 mM glutamate at normal pH. Cell swelling and viability were quantified by flow cytometry. Lactacidosis of …