Plasma Osmolality and Brain Water Content in a Rat Glioma Model

Neurosurgery ◽  
1994 ◽  
Vol 34 (3) ◽  
pp. 505???511 ◽  
Author(s):  
Thomas D. Hansen ◽  
David S. Warner ◽  
Vincent C. Traynelis ◽  
Michael M. Todd
Neurosurgery ◽  
1994 ◽  
Vol 34 (3) ◽  
pp. 505-511 ◽  
Author(s):  
Thomas D. Hansen ◽  
David S. Warner ◽  
Vincent C. Traynelis ◽  
Michael M. Todd

1993 ◽  
Vol 5 (4) ◽  
pp. 293
Author(s):  
D. S. Warner ◽  
T. D. Hansen ◽  
V. C. Traynelis ◽  
M. M. Todd

2002 ◽  
Vol 96 (2) ◽  
pp. 416-421 ◽  
Author(s):  
Kokila Thenuwara ◽  
Michael M. Todd ◽  
Johnny E. Brian

Background Mannitol and furosemide are used to reduce increased intracranial pressure (ICP) and to reduce brain bulk during neurosurgery. One mechanism by which these changes might occur is via a reduction in brain water content. Although mannitol and furosemide are commonly used in combination, there has been no formal evaluation of the interactive effects of these two drugs on brain water. The effect of mannitol and furosemide alone and in combination on water content of normal rat brain was examined. Methods The lungs of rats anesthetized with halothane were mechanically ventilated to maintain normal physiologic parameters. After baseline measurement of plasma osmolality, mannitol (1, 4, or 8 g/kg), furosemide (2, 4, or 8 mg/kg), or a combination of furosemide (8 mg/kg) and mannitol (1, 4, or 8 g/kg) was administered intravenously over approximately 15 min. One hour later, plasma osmolality was measured, the animals were killed, and brain water content was determined by wet and dry weight measurements. Results Mannitol produced a dose-dependent increase in plasma osmolality and reduction of brain water content. There was a linear relation between plasma osmolality and brain water content. Furosemide alone did not affect plasma osmolality or brain water at any dose. The combination of furosemide with mannitol resulted in a greater increase in plasma osmolality than seen with mannitol alone and a greater decrease in brain water at 4 and 8 g/kg of mannitol. Conclusions The doses of mannitol and furosemide utilized were much larger than clinically applicable doses and were selected to maximize the ability to detect effect on brain water. The combination of mannitol and furosemide resulted in greater reduction of brain water content than did mannitol alone. Furosemide enhanced the effect of mannitol on plasma osmolality, resulting in a greater reduction of brain water content. Potential interaction (if any) of smaller, clinically used doses of mannitol and furosemide cannot be surmised from the current study.


2006 ◽  
Vol 105 (6) ◽  
pp. 1176-1181 ◽  
Author(s):  
Michael M. Todd ◽  
Johann Cutkomp ◽  
Johnny E. Brian

Background Furosemide and mannitol are used to reduce intracranial pressure, but the impact of furosemide on edema of injured brain is unclear. The authors examined the effects of furosemide and mannitol, alone and in combination, on brain water content in brain-injured rats. Methods Anesthetized rats were subjected to a 2.2-atm left hemispheric fluid percussion injury. Two and three-quarters hours later, animals received 0.5, 1, 4, or 8 g/kg mannitol; 8 mg/kg furosemide; a combination of 4 g/kg mannitol plus 4 mg/kg furosemide; or 8 g/kg mannitol plus 8 mg/kg furosemide. One hour later (4 h after injury), plasma osmolality was measured, and hemispheric water content was determined by drying. Other animals were subjected to injury without drug treatment (impact only) or did not undergo injury (control). Pairwise group comparisons regarding the effects of mannitol and furosemide were restricted to only four groups: impact only, 8 g/kg mannitol, 8 mg/kg furosemide, and 8 g/kg mannitol plus 8 mg/kg furosemide. Results The water content of both hemispheres in the impact-only group was greater than in the control group (left greater than right). Mannitol, 8 g/kg, increased osmolality from 306 +/- 4 to 351 +/- 6 mOsm/kg (mean +/- SD) and reduced water content in the left hemisphere from 80.06 +/- 0.84% (impact only) to 78.24 +/- 0.73%. Furosemide, 8 mg/kg, had no effect on osmolality or water content. Brain water in animals treated with 8 g/kg mannitol plus 8 mg/kg furosemide did not differ from that seen with 8 g/kg mannitol alone. Conclusions Mannitol increased plasma osmolality and reduced water content of the injured and contralateral hemispheres, whereas the authors observed no effect of furosemide when given either alone or in combination with mannitol.


1986 ◽  
Vol 250 (3) ◽  
pp. R444-R451 ◽  
Author(s):  
J. G. Verbalis ◽  
E. F. Baldwin ◽  
A. G. Robinson

Endogenous pituitary secretion of vasopressin (AVP) and oxytocin (OT) was studied in rats with induced dilutional hyponatremia that was sustained for 2-5 days. Graded infusions of hypertonic saline produced progressive increases in plasma osmolality, but despite large relative increases in osmolality, AVP and OT secretion was not significantly stimulated until plasma [Na+] reached normal ranges. Regression analysis of plasma AVP and OT levels once secretion was stimulated showed no significant shift of the osmotic threshold for neurohypophyseal secretion of either hormone, as well as equivalent slopes of plasma AVP and OT increases per unit increases in plasma osmolality, in the hyponatremic rats relative to normonatremic controls. After a 20-25% decrease in plasma osmolality, total brain water content of hyponatremic rats increased only 3-6%, whereas larger decreases (11-17%) in total brain electrolytes were found. During subsequent hypertonic saline infusions in the hyponatremic rats total brain water content decreased linearly, resulting in brain dehydration below normal total brain water levels before stimulation of AVP and OT secretion occurred. The stability of the osmotic threshold for neurohypophyseal secretion, despite evidence of brain adaptation to chronic hypotonicity, argues that cell volume regulation via solute loss is not a likely cause of resetting of the osmostat. Additionally, brains of hyponatremic rats were found to manifest significantly greater susceptibility to dehydration after hypertonic saline infusions than brains of normonatremic controls, which may be a consequence of brain solute loss from adaptation to chronic hypotonicity.


2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.


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