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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.
Stroke 1990 Oct
PMID:Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. 221 11

Functional assessment of animals following experimental cerebral ischemia is often difficult due to the passive nature of many neurologic exams. We attempted to increase the objectivity of motor function evaluation by adapting quantifiable behavioral tests and actively testing rats' motor capability following a cerebral ischemic insult. It was hypothesized that active testing would reveal motor deficits which were not readily apparent upon casual observation and that such testing would provide a more sensitive means of experimental neurologic assessment. Wistar rats were exposed to reversible severe forebrain ischemia using the four-vessel occlusion technique. Motor function was evaluated using the total motor score (sum of scores for screen test, balance beam test, and prehensile-traction test) over the 48 hours which followed 20 minutes of cerebral ischemia. To manipulate neurologic outcome, rats were fed or fasted the day prior to ischemia and then pretreated with either 1,3-butanediol or saline. Fasted saline-treated animals demonstrated improved total motor performance compared with fed animals by 48 hours after ischemia. There was no improvement in motor performance by fasted vs. fed rats from among the butanediol-treated animals. Pretreatment with butanediol resulted in significantly better total motor performance among fasted rats 24 hours after ischemia; however, by 48 hours postischemia, no difference was detectable. This is the first demonstration of motor deficits produced by four-vessel occlusion in rats. The motor tests devised appear to be adequately sensitive to detect changes in motor function that are not apparent with passive observation in this model.
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PMID:Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol. 356 10

1,3-Butanediol is an ethanol dimer that induces systemic ketosis. It has previously been shown to increase hypoxic survival time and reduce neurologic deficit in several experimental preparations. The aim of this study was to determine if the mechanism of 1,3-butanediol-induced cerebral protection was elevation of blood ketone levels, blood glucagon levels, or both. Blood beta-hydroxybutyrate levels, glucagon levels, or both produced by a previously reported protective dose of 1,3-butanediol (47 mmol/kg) were simulated by direct i.v. infusion of the ketone beta-hydroxybutyrate and glucagon separately and in combination, and the effect on hypoxic survival time in instrumented Levine rats (unilateral carotid ligation and hypoxic exposure) was determined. To test if the mechanism was a direct or osmotic effect of the alcohol, an equimolar dose of ethanol (47 mmol/kg) was administered and the effect on hypoxic survival time was compared with that produced by 1,3-butanediol. As in previous studies, 1,3-butanediol significantly increased hypoxic survival time (241% of control, Scheffe p less than 0.05). Various doses of beta-hydroxybutyrate and glucagon were infused to approximate the blood levels of beta-hydroxybutyrate and glucagon produced by a protective dose of 1,3-butanediol. Although beta-hydroxybutyrate or glucagon infusions produced blood levels of these substances that were comparable with those produced by administering butanediol, they failed to prolong hypoxic survival time as long as 1,3-butanediol. No correlation was detected between hypoxic survival time and blood levels of beta-hydroxybutyrate, glucagon, insulin, or glucose. An equimolar dose of ethanol did not significantly increase hypoxic survival time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated blood ketone and glucagon levels cannot account for 1,3-butanediol induced cerebral protection in the Levine rat. 381 Jul 56

The objective of this study was to determine if 1,3-butanediol would reduce a neurologic deficit in rats exposed to ischemic-hypoxia (Levine rats). Age and weight matched male Sprague-Dawley rats were anesthetized with 2% halothane. The right common carotid and external jugular vein were ligated and cannulated and EEG screws were implanted followed by a 2 hour recovery period. Thirty minutes prior to exposure the rats received either 1,3-butanediol (47 mmole/kg i.v.; n = 11) or an equal volume of saline (n = 10). The rats were then exposed to 4.5% O2 until mean arterial blood pressure fell to 70 mm Hg. The oxygen level was then increased to 8% for 30 minutes, after which the rats were returned to room air. Posture, hemiparesis, circling, shuffling, activity, and ability to hang on to a vertical screen were scored 1 (normal) to 5 (severe deficit) at 2 and 20 hours after insult. The time to 70 mm Hg was extended from 7.9 +/- 0.9 min for saline treated rats to 19.0 +/- 2.3 min for the 1,3-butanediol treated rats (p less than 0.001). All eleven 1,3-butanediol treated rats survived the hypoxic insult; 90% (9/10) saline treated rats died. In an attempt to reduce the insult, six additional saline treated rats were switched to 8% O2 at 75 mm Hg and still 4/6 died. The mean score at 20 hours for three surviving saline treated rats was 3.4. A significantly better (p less than 0.002) mean 20 hour score for the surviving 8/11 1,3-butanediol treated rats was 1.2. 1,3-butanediol increases survival and decreases the neurologic deficits associated with this ischemic-hypoxic insult.
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PMID:Reduction of neurologic deficit by 1,3-butanediol induced ketosis in levine rats. 404 49

Previously we found that 1,3-butanediol-treated mice live longer during hypoxia. We hypothesized that 1,3-butanediol could reduce the brain's accumulation of potentially cytotoxic lactate and/or elevate brain substrate availability (ketones or glucose) and thus maintain the brain's energy producing capability even during reduced oxygen availability. To test these hypotheses, whole brain metabolites from normoxic and hypoxic mice, pretreated with 1,3-butanediol or insulin, were compared to saline controls. During hypoxia both pretreated groups had lower brain lactate than controls. If lactate accumulation was the sole factor responsible for hypoxic tolerance, insulin should have increased brain lactate since insulin has been shown previously to reduce hypoxic tolerance. In normoxic mice the ratio of lactate to pyruvate and the level of malate and fumarate were not changed by 1,3-butanediol as is found with other agents known to protect the hypoxic animal. When substrate availability was directly elevated by beta-hydroxybutyrate and glucose administration hypoxic survival time increased thus implicating substrate availability as an important factor in hypoxic tolerance. We conclude that reduced brain lactate and augmented substrate availability both contribute to 1,3-butanediol-enhanced hypoxic tolerance in this animal model.
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PMID:Role of tissue lactate and substrate availability in 1,3-butanediol-enhanced hypoxic survival in the mouse. 636 95

To determine if 1,3-Butanediol (BD), which protects mice from hypoxia, would extend the tolerance of rats to ischemic-hypoxia, the Levine rat (unilateral carotid ligation and conscious hypoxic exposure) was modified to record mean arterial pressure (BP), heart rate (HR), central venous pressure (CVP), spontaneous respiration and EEG. Age and weight matched, male, Sprague-Dawley rats were anesthetized under halothane (1-2%), ligated, instrumented, and recovered 2 hrs before hypoxia (4.5% oxygen). Thirty minutes prior to hypoxia, groups of rats received, BD (47 mmoles/kg i.v.; n = 7), equal volumes of saline (S) (n = 6) or no-infusion (NI) (n = 7). Since no significant difference was observed between S and NI they were combined into a single control group (C). In a parallel group administered BD, resultant beta- hydroxybutarate ( BHB ) levels increased from 0.13 +/- 0.02 to 0.84 +/- 0.03 mM and temperature declined only 1.5 degrees C. The EEG of all ischemic-hypoxic rats invariably became isoelectric before cessation of spontaneous respiration and eventual loss of BP. BD significantly (p less than 0.01, Student's t) increased ischemic-hypoxic tolerance (time to isoelectric EEG) from 875 +/- 56 for the control group to 1338 +/- 67 seconds for the BD group, without changing the interval from isoelectric EEG to loss of BP. Further, EEG activity persisted at a lower mean BP (p less than 0.01) in the BD group (44 +/- 5 mm Hg) than in the control group (66 +/- 4 mm Hg). In summary, isoelectric EEG invariably precedes ventilatory failure and cardiovascular collapse. BD increases ischemic-hypoxic tolerance in the conscious rat by extending, at a lower mean BP, the time to isoelectric EEG.
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PMID:Butanediol induced cerebral protection from ischemic-hypoxia in the instrumented Levine rat. 672 86

In previous studies from our laboratory a positive correlation between elevated blood ketone levels and the survival time (ST) during hypoxia (4-5% oxygen) was observed in fasted and alloxan diabetic mice. To test the hypothesis that ketosis was somehow increasing the tolerance of mice to hypoxia, we induced ketosis by either oral (PO), intraperitoneal (IP), or intravenous (IV) 1,3-butanediol (BD). Blood beta-hydroxbutyrate increased from 0.33 +/- 0.06 mM to 3.32 +/- 0.08 mM for PO, 1.2 +/- 0.2 mM for IV and 0.83 +/- 0.15 mM for IP. BD was associated with an increase in ST to 458% (n = 19) when given PO, 217% (n = 12) by IP route, and 560% (n = 13) by the IV route. The effect of ambient temperature (Ta) on this phenomenon was evaluated at 12, 22, 32, and 34 degrees C. At each Ta, IV BD at 1.4 mmole/mouse was associated with an increase in ST to 525, 559, 151, and 145% of control, respectively. The absolute ST of both control and treated mice was greater at Ta of 12 and 22 degrees C. Hypoxia, however, was associated with a decrease in body temperature in each group. It is concluded that the artificial induction of ketosis by BD is associated with an increase in ST of mice exposed to hypoxia.
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PMID:Butanediol induced ketosis increases tolerance to hypoxia in the mouse. 677 94

A coorelation has been observed between increased blood ketones and the tolerance of mice to hypoxia (4-5% oxygen). In previous studies fasted mice, alloxan diabetic mice and mice given 1,3-butanediol were found to be ketotic and to have increased tolerance to hypoxia. We attempted to induce a similar increased hypoxic tolerance by direct elevation of blood ketones with IV and IP beta-hydroxybutyrate (BHB). No increase in hypoxic tolerance was observed with BHB alone. Inasmuch as fasting and alloxan diabetes are both associated with elevated blood glucagon (G), hypoxic tolerance tests were made 30 min after G alone or a combination of G plus BHB. The mice given G alone or BHB alone had hypoxic survival times not different from saline controls. The mice given G plus BHB had increased survival times that could not be explained on the basis of a G mediated alteration in blood BHB.
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PMID:Hypoxic tolerance enhanced by beta-hydroxybutyrate-glucagon in the mouse. 677 95