Effects of profound hypothermia on the blood–brain barrier permeability in acute and chronically ethanol treated rats

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Abstract

This study examines the effects of profound hypothermia on the blood–brain barrier (BBB) permeability in ethanol administrated rats. Vascular permeability to intravenously injected Evans blue (EB) was quantitatively examined in the brain regions of rats. Rats were treated with ethanol acute and chronically. Rectal temperature of rats was dropped into 20±1°C during profound hypothermia. Mean arterial blood pressure in both acute and chronic ethanol treatments plus hypothermia significantly dropped into low levels as well as in hypothermia alone (P<0.01). Hypothermia led to a significant increase in the content of EB dye in the brain regions of rats (P<0.05). Both acute and chronic ethanol treatments plus hypothermia did not lead to a significant increase in the BBB permeability against intravenously injected EB dye. We conclude that ethanol intake protects the BBB against the effects of hypothermia.

Introduction

Hypothermia and ethanol are often closely linked and in hypothermic accidents ethanol is often a contributing factor for brain as well as for other organs [1]. Eighty percent of deaths based on urban hypothermia have occurred in winter months when the outdoor temperature was between 0 and 5°C [2]. It has been shown that a high alcohol concentration had often been found in those in their 40s and 50s who died from hypothermia [2], [3]. Alcohol has been shown as the main contributing cause of deaths connected with urban hypothermia [4]. During hypothermia, ethanol stays significantly longer in circulation and this may contribute to a more profound effect from ethanol [2], [3]. Ethanol, during hypothermia, on the one hand causes an increase in blood catecholamine levels; on the other hand, it enhances the loss of body temperature [5]. Hypothermia reduces regional cerebral blood flow in the brain in situ and decreases cerebral metabolic rates for oxygen, glucose and lactate [6], [7].

Profound hypothermia has been reported to stimulate or to have no effects on BBB permeability [8], [9], [10]. Data have indicated that damage to the BBB occurs after profound hypothermia, allowing the passage of macromolecules and ions that are normally restricted from the central nervous system (CNS) [9], [10], [11], [12]. However, the mechanisms that govern BBB permeability during ethanol intake plus hypothermia are not well understood. Understanding these mechanisms could be important in hypothermic and ethanol-related deaths for forensic medicine.

Previous reports have provided contradictory results on whether ethanol alone increases or decreases the BBB permeability to various tracers [13], [14]. However, it has been reported that the BBB permeability increased to a tracer, horseradish peroxidase, after giving ethanol and pentobarbital together [15]. Braun and Juhl suggested that ethanol protects the myocardium against arrhythmia in hypothermia [16]. The BBB permeability in acute hypertension during profound hypothermia increased more than in normothermic conditions [17]. Nevertheless, the data concerning the changes of BBB permeability during acute and chronic ethanol treatment plus profound hypothermia is less clear.

To get more insight into this problem, we investigated the effect of profound hypothermia induced during both acute and chronic ethanol intake on the permeability of BBB by using a macromolecular tracer, Evans blue, widely used to evaluate the integrity of the BBB.

Section snippets

Materials and methods

Adult male Wistar rats weighing between 230 and 300 g were used for all experiments. Rats were allowed free access to food and water before the experiments. Rats were randomly allocated into six experimental groups; saline treatment (group I, n=10), acute ethanol treatment (group II, n=10), chronic ethanol treatment (group III, n=10), hypothermia (group IV, n=10), acute ethanol treatment plus hypothermia (group V, n=10), and chronic ethanol treatment plus hypothermia (group VI, n=10). Rats were

Results

Mean arterial blood pressure (MABP) and body weight in all groups are shown in Table 1. The MABP values were significantly dropped in animals with hypothermia compared with those in normothermic groups (P<0.05, P<0.01). The body weight of rats with chronic alcohol treatment dropped at the end of 4 months (Table 1). Hypothermic groups demonstrated a greater rate of temperature decline, and furthermore, chronic alcoholic rats with cold water exposure took less time to reach the rectal temperature

Discussion

The results of this study show for the first time that profound hypothermia does not affect the BBB permeability to EB during both acute and chronic ethanol treatments. Both acute and chronic ethanol treatments produced a protection on the permeability of BBB against hypothermia (Fig. 2). This study also showed that the BBB permeability did not increase after both acute and chronic ethanol treatments in normothermic conditions. The results indicated in this study agree with the studies that

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