Effects of Shan-dou-gen (Euchresta formosana) on metabolic, respiratory and vasomotor activities as well as body temperature in rats

The effects of the Chinese herb Shan-dou-gen, Euchresta formosana, on metabolic, respiratory and vasomotor activities as well as body temperature were assessed in conscious rats at various ambient temperatures. Systemic administration of Shan-dou-gen produced a dose-dependent hypothermia in rats at room temperature (22 degrees C) and below. The hypothermia in response to Shan-dou-gen was brought about by both cutaneous vasodilatation and decreased metabolic heat production. There were no changes in respiratory evaporative heat loss. However, in the heat (30 degrees C), administration of Shan-dou-gen produced no changes in rectal temperature or other thermoregulatory variables. Furthermore, the hypothermia induced by Shan-dou-gen was greatly antagonized by pretreatment of animals with 5,6-dihydroxytryptamine (predominantly a depletor of central serotonin nerve fiber), but not with 6-hydroxydopamine (a relative depletor of central catecholamine nerve fiber). It appears that the hypothermic effects of Shan-dou-gen may be mediated through serotonin release within the brain.     

Biphasic changes in body temperature produced by intracerebroventricular injections of histamine in the cat

1. Intracerebroventricular administration of histamine to cats caused hypothermia followed by a rise in body temperature. 2-Methylhistamine caused a similar biphasic response, while 3-methylhistamine had no effect on body temperature and 4-methylhistamine produced a delayed hyperthermia. Some tolerance to the hypothermic activity developed when a series of closely spaced injections of histamine was given. 2. Doses of histamine and 2-methylhistamine which altered body temperature when given centrally were ineffective when infused or injected I.V. 3. Pyrilamine, an H1-receptor antagonist, prevented the hypothermic response to histamine. 4. Hypothermic responses to histamine at an environmental temperature of 22 degrees C were comparable to responses in a cold room at 4 degrees C in both resting animals and animals acting to depress a lever to escape an external heat load. A change in error signal from the thermostat could account for these results. However, lesser degrees of hypothermia developed when histamine was given to animals in a hot environment. In some, but not all animals, this smaller response could be attributed to inadequate heat loss in spite of maximal activation of heat-loss mechanisms. 5. The hyperthermic response to histamine was antagonized by central, but not peripheral, injection of metiamide, an H2-receptor antagonist. 6. The results indicate that histamine and related agents can act centrally to cause both hypothermia, mediated by H1-receptors, and hyperthermia, mediated by H2-receptors.     

Success rate of cytogenetic analysis at the time of second-trimester dilation and evacuation

Hypoxia elicits a number of compensatory responses in animals, including behavioral hypothermia. The hypothesis that hypoglycemia induces hypothermia in the bullfrog Rana catesbeiana was tested and that this behavioral response would be beneficial. Frogs equipped with a temperature probe were tested in a thermal gradient (10-40 degrees C). Insulin (15 IU kg-1) caused significant reduction of body temperature, from 25.0 to 17.8 degrees C. A non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG, 50 mg kg-1), which blocks intracellular glucose utilization, was also injected and caused a similar drop in body temperature, despite an increase in plasma glucose levels. To assess the possible benefits of hypoglycemia-induced hypothermia, the effects of insulin and 2-DG injections were measured on plasma glucose concentration and on oxygen consumption of frogs equilibrated at 10, 20 and 30 degrees C. The plasma glucose was elevated at higher temperatures and so was oxygen consumption. The insulin caused a significant reduction of plasma glucose concentration (about 1.22 muMol ml-1) whereas 2-DG caused a significant increase (about 0.70 muMol ml-1) at 30 degrees C. Both drugs caused a reduction of oxygen consumption (approximately 0.388 and 0.382 ml min-1 kg at 30 degrees C after insulin and 2-DG injection, respectively). No effect of either insulin or 2-DG was observed when the animals were equilibrated at 10 degrees C. In conclusion, hypothermia may be a beneficial response to hypoglycemia in frogs.     

Prior hypothermia attenuates malignant hyperthermia in susceptible swine

This study was designed to determine the extent by which mild or moderate hyperthermia attenuates the triggering of malignant hypothermia (MH) induced by the combined administration of halothane and succinylcholine. Sixteen susceptible swine were initially anesthetized with nontriggering drugs and then either kept normothermic (approximately equal to 38 degrees C, n = 6) or cooled to induce mild (approximately equal to 35 degrees C, n = 6), or moderate (approximately equal to 33 degrees C, n = 4) hypothermia. Next, after a 30-min control period, the normothermic and mildly hypothermic animals were administered 1 minimum alveolar anesthetic concentration (MAC) halothane followed by a bolus dose of succinylcholine (2 mg/kg). Within 10 min all normothermic animals developed fulminant MH, whereas the onset of MH was slowed or was absent in the mildly hypothermic group. To test whether moderate hypothermia could more effectively minimize the signs of a MH episode, this group of animals was exposed to 1.5 MAC halothane followed 10 min later by a 3-mg/kg bolus of succinylcholine. MH was not induced and anesthesia was then changed to nontriggering drugs (ketamine and pancuronium). The animals were then aggressively rewarmed to 38 degrees C: a slight increase in the ETCO2 was detected, but MH episodes did not spontaneously occur. Subsequently, the readministration of halothane and succinylcholine rapidly provoked fulminant MH. We concluded that the induction of mild hypothermia impairs triggering and reduces the progression of MH induced by the combined administration of halothane and succinylcholine, whereas moderate hypothermia was completely protective and thus could be considered for prophylaxis.     

Structure and expression of bombyxin E1 gene: a novel family gene that encodes bombyxin-IV, an insect insulin-related neurosecretory peptide

Comparison was made of the ability of two dihydropyridine calcium channel antagonists, nitrendipine and felodipine, to prevent a range of signs of ethanol withdrawal. The increases in handling-induced behavior seen in mice during withdrawal from chronic ethanol treatment were prevented by administration of nitrendipine, 50 mg/kg, but not by, felodipine, 10 mg/kg, a dose that caused a similar displacement of dihydropyridine binding in central nervous system tissue, in vivo and in vitro. A higher dose of felodipine, 20 mg/kg, also had no effects. Nitrendipine, but not felodipine, prevented audiogenic seizures during the withdrawal phase. Similarly, nitrendipine prevented both the decrease in thresholds for N-methyl-DL-aspartate seizures and the increase in thresholds for convulsions due to 4-aminopyridine, which were seen during the withdrawal period, while felodipine did not alter either of these changes. Withdrawal from the ethanol chronic treatment increased the thresholds to seizures produced by intravenous aminophylline; this change was also prevented by nitrendipine. The significance of this increase in thresholds was lost after felodipine administration. In naive mice (not treated with ethanol) the doses of nitrendipine and felodipine used in the withdrawal studies were tested against the effects of convulsant drugs. Both dihydropyridines increased, to similar extents, the thresholds for seizures produced by bicuculline, pentylenetetrazol, and by N-methyl-DL-aspartate. The thresholds for aminophylline were unaltered by either dihydropyridine. In contrast, the thresholds for seizures due to 4-aminopyridine in the naive animals were not changed by felodipine, but were increased by nitrendipine. The results suggest that changes in potassium, as well as calcium, may possibly be involved in some of the stages of the ethanol withdrawal syndrome.     

The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome

The effects of the anticonvulsant, gabapentin, were investigated, in mice, on the withdrawal convulsive behaviour and anxiety-related behaviour that are produced by cessation of prolonged intake of ethanol. When given at 50 or 100 mg/kg, this compound decreased the rise in handling-induced hyperexcitability which occurs during the withdrawal period; the effects were most pronounced for the first 4 hr after administration. Gabapentin also decreased the convulsive response to an audiogenic stimulus during the withdrawal period. The elevated plus-maze, with both traditional and ethological indices of activity was used as a test of anxiety-related behaviour after cessation of chronic ethanol treatment. Gabapentin, at 50 and 100 mg/kg, was found to decrease some, although not all, of the signs of withdrawal-induced anxiety. At doses up to and including 200 mg/kg, gabapentin had no effect on motor co-ordination or spontaneous locomotor activity in control animals. The results demonstrated that gabapentin has a selective action in decreasing both convulsive and anxiety-related aspects of withdrawal behaviour after chronic ethanol treatment. It is possible that further studies with this compound may shed further light on the mechanisms involved in the withdrawal syndrome.     

Ethanol anapyrexia in rats

In the present series of experiments we tested whether ethanol decreases body temperature by impairing thermal regulation (poikilothermia) or by shifting the set point downwards. The central temperature of rats kept in a thermocline and the selected ambient temperature were recorded by telemetry. After an IP injection of 2 g/kg of ethanol the rats selected an ambient temperature 7 degrees C lower than the one they selected before the ethanol injection and 8 degrees C lower than the one selected by the same rats after saline injection. At the same time the central temperature decreased by 2.5 degrees C. After about 40 min the rats preferred warmer ambient temperatures and 10 min later the central temperature began to rise. When, after ethanol, the rats were kept at 30 degrees C the central temperature remained at the normal level. At 35-36 degrees C the central temperature of normal rats without ethanol rose, in 1 h, from 37 degrees C to 39.75 degrees C. The results suggest that ethanol hypothermia is due to a downward shift of the set point and, in fact, is an anapyrexia, a condition inverse to fever.     

V(H) repertoire of a marsupial (Monodelphis domestica)

We have been using a genetic strategy to define the contribution of specific candidate genes, such as those encoding subunits of the gamma-aminobutyric acid type A receptor, to various ethanol sensitive responses. We have used the gene knockout approach in mouse embryonic stem cells to create mice in which the gene encoding the alpha6 subunit of the gamma-aminobutyric acid type A receptor is rendered nonfunctional. In the present report, we provide a detailed characterization of several behavioral responses to ethanol in these null allele mice. In a separate series of experiments, behavioral response to ethanol was compared between two inbred strains of mice that are commonly used as background stock in knockout experiments, namely C57BL/6J and Strain 129/SvJ. Wild type (alpha6+/+) and homozygous null allele (alpha6-/-) mice did not differ to the ataxic effects of ethanol on acute functional tolerance (95.8 +/- 8.7 vs. 98.8 +/- 5.7 mg/dl +/- SEM, respectively). Withdrawal hyperexcitability was assessed following chronic exposure to ethanol vapor (EtOH) or air (CONT) in inhalation chambers in a multiple withdrawal treatment paradigm. At the end of the last treatment cycle, mice were scored for handling induced convulsions (HIC). After adjusting for differences in blood ethanol concentration between genotypes at the end of the final treatment cycle, we observed a greater area under the 24-hr HIC curves in mice treated with ethanol (p < 0.0001) but did not detect an effect of genotype (alpha6+/+/CONT 3.1 +/- 2.0; alpha6-/-/CONT 5.5 +/- 2.5; alpha6+/+/EtOH 30.1 +/- 6.2; alpha6-/-/EtOH 33.0 +/- 5.8 mean units +/- SEM). We also examined these mice for differences in protracted tolerance; at approximately 26 hr into the final withdrawal cycle, each mouse was injected with ethanol (3.5 mg/g body weight) and sleep time was measured. We detected a significant effect of treatment (p < 0.001) with ethanol-treated mice demonstrating signs of tolerance as reflected by a reduction in duration of sleep time. However, effect of genotype was not significant (alpha6+/+/CONT 57.4 +/- 7.6; alpha6-/-/CONT 59.0 +/- 7.6; alpha6+/ +/EtOH 34.8 +/- 7.4; alpha6-/-/EtOH 30.8 +/- 5.6 min +/- SEM). From these data we conclude that the alpha6 subunit of the GABA(A)-R exerts little if any influence on acute functional tolerance, withdrawal hyperexcitability, or protracted tolerance. Strain 129/SvJ and C57BL/6J mice were also compared for acute functional tolerance and were found not to differ (96.3 +/- 4.4 vs. 94.8 +/- 11.3 mg/dl +/- SEM, respectively). Withdrawal hyperexcitability was assessed by comparing the area under the 24 hr HIC curves. Strain 129/SvJ mice displayed a much greater basal HIC response compared to C57BL/6J mice (19.8 +/- 4.3 vs. 0.2 +/- 0.2 mean units +/- SEM, respectively); after adjusting for differences in blood ethanol concentration between strains at the end of the final ethanol treatment cycle, the HIC response was markedly enhanced by ethanol treatment in Strain 129/SvJ mice but not in C57BL/6J mice (50.4 +/- 3.1 vs. 9.5 +/- 5.4 mean units +/- SEM, respectively). The effects of treatment (p < 0.0001), strain (p < 0.0001), and the interaction of strain with treatment (p < 0.01) were significant. Since many gene knockout mice are maintained on a mixed genetic background of Strain 129/SvJ and C57BL/6J, we conclude that significant differences in tests of withdrawal hyperexcitability may be confounded by the influence of genes that cosegregate with the gene targeted allele.     

Rapid development of tolerance to the hypothermic effect of ethanol in mice

The hypothermic response to i.p. injection of ethanol (2.0-4.0 g/kg) in mice was found to be attenuated by a single equivalent ethanol injection given 24 hr earlier. The diminished hypothermic response was not an artifact since it could not be attributed to changes in body weight and was independent of familiarity with test environment and procedures. A parallel shift in the dose-response curve was found. It appears, therefore, that the reduced change in body temperature is indicative of tolerance. If the second ethanol injection was given 48 or 72 hr later, tolerance could no longer be seen. With injections spaced 24 hr apart, a third administration of ethanol did not further increase the tolerance seen after the second injection. Since blood ethanol levels did not differ in tolerant and nontolerant mice, and since tolerance was already present 10 min after the second ethanol injection, a functional rather than a metabolic tolerance is likely.     

Conspiring to succeed: the process of a joint military health care merger

The exact mechanism of hypothermic cerebroprotection after traumatic brain injury (TBI) is not fully understood. The present study was conducted to investigate the effects of mild hypothermia on trauma-induced synthesis of nitric oxide (NO), which has been implicated in the pathogenesis of ischemic brain damage associated with glutamate neurotoxicity. Cerebral contusion was created in the rat parietal cortex by a weight-drop method, and extracellular concentrations of the NO end products nitrite and nitrate were measured using in vivo brain microdialysis and capillary electrophoresis under normothermic (37 degrees C) and mild hypothermic (32 degrees C) conditions. In normothermic animals, the level of NO end products increased markedly 10 min after contusion, reaching a maximum level at 20 min. In the hypothermic rats, such increases were absent. Although it is unknown whether endothelial NO synthase, neuronal NO synthase, or both caused the elevation of the NO end products seen in the normothermic animals, the present results indicate that inhibition of NO synthesis may play a part in hypothermic cerebroprotection following TBI.     

Results of systematic speech sound monitoring in children with cleft palate

Two potent inhibitors of nitric oxide synthase (NOS), namely, NG-nitro-L-arginine (NNA) and NG-monomethyl-L-arginine (NMMA) were administered intracerebroventricularly (i.c.v.) in morphine-dependent mice to investigate their effects on abrupt withdrawal and naltrexone-precipitated abstinence signs. Male Swiss-Webster mice were rendered dependent on morphine by subcutaneous implantation of a morphine pellet containing 75 mg of morphine base. Mice implanted with placebo pellets served as controls. NMMA or NNA administered i.c.v. had minimal effects on body weight loss and hypothermia that occur during abrupt withdrawal of morphine. When administered i.c.v., both NNA or NMMA (0.1, 1 and 10 micrograms/mouse) dose-dependently inhibited naltrexone-induced stereotyped jumping behavior in mice. I.c.v. administration of NMMA also attenuated withdrawal induced fecal pellet formation. This effect, however, was not dose-dependent. In conclusion, these results suggest that brain NO plays an important role in the expression of behavioral signs of morphine withdrawal syndrome. In addition, these results support the idea that NOS inhibitors may be potentially useful in the treatment of opioid withdrawal syndrome.     

Conditioning and extinction of tolerance to the hypothermic effect of ethanol in rats.

Examined the contribution of classical conditioning to tolerance to the hypothermic effect of ethanol in 56 male albino rats. During the tolerance acquisition phase, Ss were exposed at 4-day intervals to a distinctive set of environmental cues paired with injections of ethanol (1.4 g/kg, ip). Interspersed between these drug trials were exposures to an alternate set of cues paired with injections of saline. In addition, 3 groups experienced different amounts of stimulation and activity during drug exposure in order to determine whether "behavioral augmentation" of tolerance would occur. In subsequent tests, Ss were tolerant only in the presence of cues previously paired with ethanol. Moreover, this environmentally specific tolerance was associated with a conditioned hyporthermic response to placebo (saline) injections in the drug environment. An extinction procedure designed to weaken tolerance mediated by classical conditioning was also found to be effective. Evidence for conditioned tolerance was weakest in Ss experiencing low levels of activity during the initial drug exposure periods. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lowering ambient or core body temperature elevates striatal MPP+ levels and enhances toxicity to dopamine neurons in MPTP-treated mice

The neuroprotective effects of lowering body temperature have been well documented in various models of neuronal injury. The present study investigated the effects a lower ambient or core body temperature would have on damage to striatal dopamine (DA) neurons produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice received systemic MPTP treatment at two different temperatures, 4 degrees C and 22 degrees C. MPTP-treated mice maintained at 4 degrees C demonstrated (1) a greater hypothermic response, (2) a significant reduction in striatal DA content and tyrosine hydroxylase (TH) activity, and (3) significantly greater striatal 1-methyl-4-phenylpyridinium (MPP+) levels, as compared to mice dosed with MPTP at room temperature. Parallel studies with methamphetamine (METH) were conducted since temperature appears to play a pivotal role in the mediation of damage to DA neurons by this CNS stimulant in rodents. As previously reported, METH-induced hyperthermia and the subsequent loss of striatal DA content were attenuated in animals dosed at 4 degrees C. We also evaluated the effects a hypothermic state induced by pharmacological agents would have on striatal neurochemistry and MPP+ levels following MPTP treatment. Concurrent administration of MK-801 or 8-OHDPAT increased the striatal MPP+ levels following MPTP treatment. However, only 8-OHDPAT potentiated the MPTP-induced decrements of striatal DA content and TH activity; MK-801 did not affect MPTP decreases in these striatal markers of dopaminergic damage. Altogether, these findings indicate that temperature has a profound effect on striatal MPP+ levels and MPTP-induced damage to DA neurons in mice.     

Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions

The effects of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, LY235959, were determined on the analgesic and hypothermic effects as well as on the development of tolerance to these effects of U-50,488H, a kappa-opioid receptor agonist in mice and rats. In the mouse, a single injection of LY235959 given 10 min prior to U-50,488H did not modify the analgesic action of the latter. Similarly, chronic administration of LY235959 twice a day for 4 days did not modify U-50,488H-induced analgesia in mice. Repeated pretreatment of mice with LY235959 dose-dependently attenuated the development of tolerance to the analgesic actions of U-50,488H. In the rat, LY235959 by itself produced a significant analgesia and prior treatment of rats with LY235959 enhanced the analgesic action of U-50,488H. Similar effects were seen with the hypothermic action. Pretreatment of rats with LY235959 attenuated the development of tolerance to the analgesic but not to the hypothermic action of U-50,488H. These results provide evidence that LY235959 produces differential actions on nociception and thermic responses by itself and when given acutely with U-50,488H in mice and rats. However, when the animals are pretreated with LY235959, similar inhibitory effects are observed on the development of tolerance to the analgesic action of U-50,488H in both the species. These studies demonstrate an involvement of the NMDA receptor in the development of kappa-opioid tolerance and suggest that the biochemical consequences of an opioid's interaction with the opioid receptor are not the only factors that contribute to the acute and chronic actions of opioid analgesic drugs.     

Chronic ethanol consumption: from neuroadaptation to neurodegeneration

In this review first we evaluate evidence on the role of the neurobiological alterations induced by chronic ethanol consumption in the development of ethanol tolerance, dependence and withdrawal. Secondly, we describe the neuropathological consequences of chronic ethanol on cognitive functions and on brain structures. Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. While tolerance mechanisms are unlikely to contribute to the neuroadaptive changes associated with ethanol dependence, it is otherwise clear that repeated high, intoxicating doses of ethanol trigger those neuroadaptive processes that lead to dependence and contribute to the manifestation of the abstinence syndrome upon withdrawal. An unbalance between inhibitory and excitatory neurotransmission is the most prominent neuroadaptive process induced by chronic ethanol consumption. Due to the diffuse glutamatergic innervation to all brain structures, the neuroadaptive alterations in excitatory neurotransmission can affect the function of most if not all of neurotransmitter systems. The expression of the withdrawal syndrome is the major causal factor for the onset and development of the neuropathological alterations. This suggests a link between the neuroadaptive mechanisms underlying the development of ethanol dependence and those underlying the functional and structural alterations induced by chronic ethanol. In animals and humans, specific alterations occur in the function and morphology of the diencephalon, medial temporal lobe structures, basal forebrain, frontal cortex and cerebellum, while other subcortical structures, such as the caudate nucleus, seem to be relatively spared. The neuropathological alterations in the function of mesencephalic and cortical structures are correlated with impairments in cognitive processes. In the brain of alcoholics, the prefrontal cortex and its subterritories seem particularly vulnerable to chronic ethanol, whether Korsakoff's syndrome is present or not. Due to the role of these cortical structures in cognitive functions and in the control of motivated behavior, functional alterations in this brain area may play an important role in the onset and development of alcoholism.     

Screening for ENU-induced mutations in mice that result in aberrant ethanol-related phenotypes.

One way to investigate the genetic underpinnings of ethanol-related phenotypes is to create random mutations and screen the mutagenized mice for their behavioral phenotypes. The purposes of this article are to assess the efficacy of a novel high throughput screen to detect known strain differences and to provide evidence of the ability of this screen to detect phenodeviants, as illustrated by two new lines of mutant mice. All mice were tested for the following phenotypes after a dose of 2.25 g/kg of ethanol: ataxia, anxiolytic response, locomotor activity, core body temperature, and blood ethanol concentration, as well as ethanol consumption based on a two-bottle choice test. The authors obtained several baseline measures that allowed for the detection of phenodeviants on these measures as well. To validate this screen, A/J, DBA/2J, and C57BL/6J mouse strains were tested, and previously reported strain differences were found in all phenotypes except ethanol-induced hypothermia. Additionally, two mutant pedigrees were identified: 7TNJ, which exhibited abnormal ethanol-induced locomotor activity, and 112TNR, which exhibited an enhanced ability on the rotarod. These data demonstrate the efficacy of this screen to detect known as well as novel phenotypic differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The street food culture of Guatemala City: a case study from a downtown, urban park

A number of experimental studies have reported that moderate hypothermia can produce significant protection against behavioral deficits and/or morphopathological alterations following traumatic brain injury; a Phase 3 clinical trial is currently examining the therapeutic potential for moderate hypothermia (32 degrees C) to improve outcome following severe traumatic brain injury in humans. The current study examined whether hypothermia (32 degrees C) provided behavioral protection following experimental cortical impact injury. The extent of focal cortical contusion was also examined in the same rats. A total of 30 male Sprague-Dawley rats were trained on beam balance and beam walking tasks prior to injury. Under isoflurane anesthesia, cortical impact was produced on the right parietal cortex of 20 rats. Ten rats underwent all surgical procedures but were not impacted (sham-injured rats). Ten of the injured rats were cooled to 32 degrees C (measured in temporalis muscle) beginning 5 min postinjury, maintained for 2 h and rewarmed slowly for 1 h. In the other 10 injured rats, normothermic temperatures (37.5 degrees C) were maintained for the same duration. Beam balance and beam walking performance was assessed daily for 5 days following injury. At 11 days postinjury, rats were assessed for 5 days on acquisition of the Morris water maze task. Following behavioral assessments, rats were perfused and the brain removed. Coronal sections were cut through the site of cortical impact injury and stained with hematoxylin and eosin. Hypothermic treatment resulted in significantly less beam balance and beam walking deficits than observed in normothermic rats. Hypothermia also significantly attenuated spatial memory performance deficits. Quantitative morphometric analyses failed to detect any significant differences in volumes of necrotic tissue cavitation in cortices of hypothermic and normothermic rats. Hypothermic treatment also had no effect on volumes of dorsal hippocampal tissue or numbers of cells in CA1 or CA3 regions of the hippocampus. These data suggest that hypothermia, consistent with the reports of others, can produce significant behavioral protection following cortical impact injury that is not necessarily correlated with changes in focal cortical necrosis within the first 15 days following injury.     

Influence of cold or hyperbaric helium-oxygen environments on mouse response to a respiratory viral infection

In investigating the stress effects of chilling (2-3 degrees C) and hypothermia (2-3 degrees C drop in body core temperature mediated by exposure to hyperbaric helium-oxygen atmosphere) on mouse resistance to "influenza," it was noted that these stresses adversely affected the course of pulmonary infection produced by aerosols of the NWS strain of influenza virus. Comparatively, respiratory LD50 values for control animals were about 25 virus plaque-forming units (PFU) with median mortality occurring on day 13. The LD50 values for mice chilled at 2-3 degrees C were about 15 PFU with median mortality on day 7, and for mice exposed to hyperbaric helium, about 12 PFU with median mortality on day 6. Cold or hyperbaric stress impaired interferon production. Impairment was observed at 24 h but not at 12 h post-challenge and persisted for several days until mice became moribund.     

Comparison of brain tissue metabolic changes during ischemia at 35 degrees and 18 degrees C

BACKGROUND: We evaluated brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during ischemia with brain temperature at 35 degrees and 18 degrees C in the same patient. METHODS: Surgery was performed in a 60-year-old woman to clip a large aneurysm in the left internal carotid artery (ICA). A Paratrend 7 probe measuring PO2, PCO2, and pH was inserted into tissue at risk for ischemia during ICA occlusion and brain protection was provided with 9% desflurane. One week later, hypothermic circulatory arrest with brain temperature at 18 degrees C was performed for aneurysm clipping and tissue measurements were obtained during ischemia and rewarming. RESULTS: At 35 degrees C, ICA occlusion for 16 minutes produced tissue hypoxia (PO2 = 0) and acidosis (pH = 6.70). The rate of increase of hydrogen ion (H+) reached 50 nEq.L(-1).min(-1) during ICA occlusion and there was a slow recovery of acidosis at the end of the ischemic period. During hypothermic circulatory arrest, tissue PO2 was sensitive to decreases in blood pressure and decreased rapidly during exsanguination. Although tissue pH decreased to 6.5 with 30 min of no pump flow, the rate of H+ increase during hypothermic arrest was one-third of that seen during ischemia at 35 degrees C. During rewarming from profound hypothermia, two phases of recovery from acidosis were observed, one during CO2 clearance and one after tissue reoxygenation. Recovery of acidosis occurred sooner at 18 degrees C than at 35 degrees C. CONCLUSIONS: These results show that tissue acidosis develops more slowly and recovers more rapidly with hypothermic ischemia. This may be an important mechanism of reduced ischemic injury during hypothermia.     

CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol

Although tolerance to cannabinoids has been well established, the question of cannabinoid dependence had been very controversial until the discovery of a cannabinoid antagonist, SR141716A. The objective of this study was to develop and characterize a mouse model of precipitated withdrawal indicative of cannabinoid dependence. Using a dosing regimen known to produce pharmacological and behavioral tolerance, mice were treated with Delta9-tetrahydrocannabinol (Delta9-THC) twice a day for 1 wk. SR141716A administration after the last Delta9-THC injection promptly precipitated a profound withdrawal syndrome. Typical withdrawal behavior was an increase in paw tremors and head shakes that was accompanied with a decrease in normal behavior such as grooming and scratching. Of the three Delta9-THC regimens tested, daily Delta9-THC injections of 10 and 30 mg/kg produced the greatest number of paw tremors and head shakes and the least number of grooms after challenge with SR141716A. Precipitated withdrawal was apparent after 2, 3, 7 and 14 days of treatment based on an increase in paw tremors in Delta9-THC-treated mice as compared with vehicle-treated mice. These findings are consistent with SR141716A-precipitated withdrawal in rats. Moreover, these results suggest that mice are a viable model for investigating dependence to cannabinoids.