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Biomedical subjects

P L Lutz

Publications and source records attributed to P L Lutz.

At least 19 recordsLinked to original sources
PubMed1999

Maintenance of adenosine A1 receptor function during long-term anoxia in the turtle brain.

It has been established that adenosine has a critical role in the extraordinary ability of the turtle brain to survive anoxia. To further investigate this phenomenon we compared rat and turtle brain adenosine A1 receptors using cyclopentyl-1,3-dipropylxanthine, 8-[dipropyl-2,3-3H(N)] ([3H]DPCPX) saturation binding analyses and determined the effects of prolonged anoxia (6, 12, and 24 h) on the adenosine A1 receptor of the turtle brain. The rat brain had a 10-fold greater density of A1 receptors compared with the turtle [rat cortex receptor density (Bmax) = 1,400 +/- 134.6 fmol/mg protein, turtle forebrain Bmax = 103.2 +/- 4.60 fmol/mg protein] and a higher affinity [dissociation constant (Kd) rat cortex = 0.328 +/- 0.035 nM, Kd turtle forebrain = 1.16 +/- 0.06 nM]. However, the turtle Kd is within the reported mammalian range, and the Bmax is similar to that reported for other poikilotherms. Unlike the mammal, in which A1 receptor function is rapidly compromised in anoxia, in the turtle forebrain no significant changes in the A1 receptor population were seen during 24-h anoxia. However, in the hindbrain, whereas the Bmax remained unchanged, the Kd significantly decreased from 2.1 to 0.5 nM after 6 h anoxia and this higher affinity was maintained at 12- and 24-h anoxia. These findings indicate that, unlike the GABAA receptor, the protective effectiveness of adenosine in the anoxic turtle brain is not related to an enhanced receptor number. Protection from a hypoxia-induced compromise in A1 receptor function and an increased A1 sensitivity in the hindbrain may be important factors for maintaining the adenosine-mediated downregulation of energy demand during long-term anoxia.

Animals↗
PubMed1998

Low extracellular dopamine levels are maintained in the anoxic turtle (Trachemys scripta) striatum.

The uncontrolled increase of extracellular dopamine (DA) has been implicated in the pathogenesis of hypoxic/ischemic damage in the mammalian brain. But unlike the harmful release of excitatory neurotransmitters such as glutamate and aspartate, which occurs on brain depolarization, excessive extracellular DA levels occur even with mild hypoxia in the mammalian brain. The purpose of this study was to determine whether hypoxia/anoxia provokes a similar increase in the anoxic tolerant turtle brain. Extracellular DA was measured in the striatum of the turtle using microdialysis followed by high-performance liquid chromatography analysis. Results show that extracellular DA was held to normoxic levels over 4 hours of anoxia. Treatment with the specific DA transport blocker GBR 12909 during anoxia resulted in a significant increase in DA to 236% over basal levels. The ability to maintain low striatal extracellular DA may be an important adaptation for anoxic survival in the turtle brain; a contributing factor is the continued functioning of DA uptake mechanisms during anoxia.

Animals↗
PubMed1998

ATP-sensitive K+ channel activation provides transient protection to the anoxic turtle brain.

There is wide speculation that ATP-sensitive K+ (KATP) channels serve a protective function in the mammalian brain, being activated during periods of energy failure. The aim of the present study was to determine if KATP channels also have a protective role in the anoxia-tolerant turtle brain. After ouabain administration, rates of change in extracellular K+ were measured in the telencephalon of normoxic and anoxic turtles (Trachemys scripta). The rate of K+ efflux was reduced by 50% within 1 h of anoxia and by 70% at 2 h of anoxia, and no further decrease was seen at 4 h of anoxia. The addition of the KATP channel blocker glibenclamide or 2,3-butanedione monoxime prevented the anoxia-induced decrease in K+ efflux during the first hour of anoxia, but the effect of these blockers was diminished at 2 h of anoxia and was not seen after 4 h of anoxia. This pattern of change in KATP channel blocker sensitivity can be related to a previously established temporary fall and subsequent recovery of tissue ATP during early anoxia. We suggest that activated KATP channels are involved in the downregulation of membrane ion permeability (channel arrest) during the initial energy crisis period but are switched off when the full anoxic state is established and tissue ATP levels have been restored. We also found that, in contrast to those in mammals, KATP channels are not a major route for K+ efflux in the energy-depleted turtle brain.

Adenosine Triphosphate↗
PubMed1997

Brain Na+/K+-ATPase activity in two anoxia tolerant vertebrates: crucian carp and freshwater turtle.

The crucian carp (Carassius carassius) and freshwater turtles (Trachemys scripta) are among the very few vertebrates that can survive extended periods of anoxia. The major problem for an anoxic brain is energy deficiency. In the brain, the Na+/K+-ATPase is the single most ATP consuming enzyme, being responsible for maintaining ion gradients. We here show that the Na+/K+-ATPase activity in the turtle brain is reduced by 31% in telencephalon and by 34% in cerebellum after 24 h of anoxia. Both changes were reversed upon reoxygenation. By contrast, the Na+/K+-ATPase activities were maintained in the anoxic crucian carp brain. These results support the notion that crucian carp and turtles use divergent strategies for anoxic survival. The fall in Na+/K+-ATPase activities displayed by the turtle is likely to be related to the strong depression of brain electric and metabolic activity utilized as an anoxic survival strategy by this species.

Animals↗
PubMed1997

Release of adenosine and ATP in the brain of the freshwater turtle (Trachemys scripta) during long-term anoxia.

Extracellular adenosine and ATP levels were monitored by microdialysis in the striatum of the freshwater turtle Trachemys scripta during long-term N2 respiration. After an initial rise in extracellular adenosine, a second peak of longer duration and higher in intensity, followed. The frequencies of these adenosine cycles varied considerably between individual turtles, such that the shortest time between the peaks was 80 min and the longest was 300 min (mean 151 min). After about 60 min anoxia, there was also a slow increase in extracellular ATP, rising from a normoxic concentration of 1.21 +/- 0.12 to 7.58 +/- 3.70 nmol l(-1) at 240 min anoxia. The results suggest that adenosine may continue to have a protective function in the turtle brain during long-term anoxia and that extracellular ATP might not function as an excitatory neurotransmitter in the anoxic turtle brain.

Adenosine↗
PubMed1997

Electroencephalogram activity in the anoxic turtle brain.

The anoxia-tolerant turtle brain slowly undergoes a complex sequence of changes in electroencephalogram (EEG) activity as the brain systematically downregulates its energy demands. Following N2 respiration, the root mean square voltage rapidly fell, reaching approximately 20% of normoxic levels after approximately 100 min of anoxia. During the first 20- to 40-min transition period, the power of the EEG decreased substantially, particularly in the 12- to 24-Hz band, with low-amplitude slow wave activity predominating (3-12 Hz). Bursts of high voltage rhythmic slow (approximately 3-8 Hz) waves were seen during the 20- to 100-min period of anoxia, accompanied by large sharp waves. During the next 400 min of N2 respiration, two distinct patterns of electrical activity characterized the anoxic turtle brain: 1) a sustained but depressed activity level, with an EEG amplitude approximately 20% of the normoxic control and with total EEG power reduced by one order of magnitude at all frequencies, and 2) short (3-15 s) periodic (0.5-2/min) bursts of mixed-frequency activity that interrupted the depressed activity state. We speculate that the EEG patterns seen during sustained anoxia represent the minimal or basic electrical activities that are compatible with the survival of the anoxic turtle brain as an integrated unit, which allow the brain to return to normal functioning when air respiration resumed.

Animals↗
PubMed1997

Role for adenosine in channel arrest in the anoxic turtle brain.

The remarkable ability of the turtle brain to survive anoxia is based on its ability to match energy demand flexibly to energy production. Earlier studies indicate that reduced ion leakage is an important mechanism for energy conservation during anoxia. We tested the hypothesis that extracellular adenosine plays a role in the reduction of K+ flux (channel arrest) that occurs in the anoxic turtle brain. Changes in extracellular K+ concentration ([K+]o in the in situ brain of the turtle Trachemys scripta were monitored following inhibition of Na+/K(+)-ATPase with ouabain. The time to reach full depolarization ([K+]o plateau) was three times longer in the anoxic brain than in normoxic controls and the initial rate of K+ leakage was reduced by approximately 70%. Superfusing the brain before the during anoxia with the general adenosine receptor blocker theophylline, or the specific adenosine A1 receptor blocker 8-cyclopentyltheophylline, significantly shortened the time to full depolarization in the ouabain-challenged anoxic brain and increased the rate of K+ efflux. The results suggest that adenosine A1 receptors are involved in the expression of anoxia-induced ion channel arrest in the turtle brain.

Adenosine↗
PubMed1997

Contrasting strategies for anoxic brain survival--glycolysis up or down.

Anoxia-tolerant turtles and carp (Carassius) exhibit contrasting strategies for anoxic brain survival. In the turtle brain, the energy consumption is deeply depressed to the extent of producing a comatose-like state. Brain metabolic depression is brought about by activating channel arrest to reduce ion flux and through the release of inhibitory gamma-aminobutyric acid (GABA) and the upregulation of GABAA receptors. Key glycolytic enzymes are down-regulated during prolonged anoxia. The result is a suppression of neurotransmission and a substantial depression in brain electrical activity. By contrast, Carassius remain active during anoxia, though at a reduced level. As in the turtle, there is an adenosine-mediated increase in brain blood flow but, in contrast to the turtle, this increase is sustained throughout the anoxic period. Key glycolytic enzymes are up-regulated and anaerobic glycolysis is enhanced. There is no evidence of channel arrest in Carassius brain. The probable result is that electrical activity in the brain is not suppressed but instead maintained at a level sufficient to regulate and control the locomotory and sensory activities of the anoxic carp. The key adaptations permitting the continued high level of glycolysis in Carassius are the production and excretion of ethanol as the glycolytic end-product, which avoids self-pollution by lactate produced during glycolysis that occurs in other vertebrates.

Adaptation, Physiological↗
PubMed1997

Survival of energy failure in the anoxic frog brain: delayed release of glutamate.

This study investigated the relationship between energy failure and neurotransmitter release in the frog (Rana pipiens) brain during 1-3 h of anoxia. Unlike truly anoxia-tolerant species, the frog does not defend its brain energy charge. When exposed to anoxia at 25 degrees C, there is an immediate fall in brain ATP levels, which reach approximately 20% of normoxic levels in approximately 60 min. The frog, nevertheless, survives another 1-2 h of anoxia. At 100 min of anoxia, there is an increase in extracellular adenosine concentration, probably originating from the increased intracellular adenosine concentration caused by the breakdown of intracellular ATP. Increases in the levels of extracellular glutamate and GABA do not occur until 1-2 h after ATP depletion. This response is quite unlike that recorded for other vertebrates, anoxia-tolerant or anoxia-intolerant, where energy failure quickly results in an uncontrolled and neurotoxic release of excitatory neurotransmitters. In the frog, the delay in excitotoxic neurotransmitter release may be one of the factors that allow a period of survival after energy failure. Clearly, energy failure by itself is not a fatal event in the frog brain.

Adaptation, Physiological↗
PubMed1997

Effects of inhibition of nitric oxide synthesis and of hypercapnia on blood pressure and brain blood flow in the turtle.

In the mammalian brain, nitric oxide (NO) is responsible for a vasodilatory tonus as well as the elevation of cerebral blood flow (CBF) induced by hypercapnia. There have been few comparative studies of cerebral vasoregulation in lower vertebrates. Using epi-illumination microscopy in vivo to observe CBF velocity on the brain surface (cerebral cortex), we show that turtles (Trachemys scripta) exposed to hypercapnia (inspired PCO2 = 4.9 kPa) displayed a 62% increase in CBF velocity, while systemic blood pressure remains constant. Exposing turtles to a PCO2 of 14.9 kPa caused an additional increase in CBF velocity, to 104% above control values, as well as a 30% increase in systemic blood pressure. The elevated CBF velocity during hypercapnia could not be blocked by a systemic injection of the NO synthase (NOS) inhibitor NG-nitro-L-arginine (L-NA). However, L-NA injection caused a temporary stop in CBF as well as a persistent increase in systemic blood pressure, suggesting that there is a NO tonus that is attenuated by the NOS inhibitor and that CBF is strongly dependent on this tonus, although compensatory mechanisms exist. Thus, although the cerebrovascular reaction to hypercapnia appeared to be NO-independent, the results suggest that there is a NO-dependent vasodilatory tonus affecting both cerebral and systemic blood circulation in this species.

Animals↗
PubMed1996

Anoxia tolerant animals from a neurobiological perspective.

This paper discusses the mechanisms for brain anoxia survival seen in crucian carp (Carassius carassius) and a few species of freshwater turtle (Chrysemys and Trachemys species). Comparisons are made with the hypoxic tolerant mammalian neonate brain. In the anoxic tolerant species the basic strategy for anoxia survival appears to be the maintenance of ion gradients, and thereby the avoidance of anoxic depolarization. Important facilitating factors involve having huge glycogen stores, increased blood supply to the brain, the suppression of electrical activity, increased release of inhibitory neuromodulators and neurotransmitters, upregulation of inhibitory neuroreceptors, the down-regulation of excitatory ion conductance and the down-regulation of Ca2+ channels. By contrast, for the mammalian neonate the most important causes of its increased hypoxia tolerance may be just simple consequences of the comparatively undifferentiated state of the brain of the newborn, with its lower energy requirements, slower decline in ATP and lower excitability levels acting to delay depolarization.

Adaptation, Physiological↗
PubMed1996

Role of nitric oxide in the elevation of cerebral blood flow induced by acetylcholine and anoxia in the turtle.

Nitric oxide (NO)-dependent regulation of brain blood flow has hitherto not been studied in reptiles. By observing the brain surface (telencephalon) of the freshwater turtle (Trachemys scripta) with epiillumination microscopy, we show that topical application of acetylcholine (ACh) induces an increase in CBF velocity that can be completely blocked by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was reversed by L-arginine. Also, sodium nitroprusside (SNP), which decomposes to liberate NO, caused an increase in CBF velocity. By contrast, L-NAME could not block the increase in blood flow velocity caused by anoxia. Interestingly, superfusing the brain with ACh or SNP during anoxia had no effect on the blood flow velocity. The results suggest that NO is an endogenous vasodilator in the turtle brain, mediating the effects of ACh during normoxia. By contrast, anoxia does not rely on NO as a vasodilator.

Acetylcholine↗
PubMed1995

Physiologic and clinicopathologic effects of crude oil on loggerhead sea turtles.

The physiologic and clinicopathologic effects of weathered South Louisiana crude oil exposure were studied in the laboratory in juvenile loggerhead sea turtles. Sea turtles ingested oil incidentally, and oil was observed clinging to the nares, eyes, and upper esophagus, and was found in the feces. Oiled turtles had up to a four-fold increase in white blood cell counts, a 50% reduction in red blood cell counts, and red blood cell polychromasia. Most serum blood chemistries (e.g., BUN, protein) were within normal ranges, although glucose returned more slowly to baseline values than in the controls. Gross and histologic changes were present in the skin and mucosal surfaces of oiled turtles, including acute inflammatory cell infiltrates, dysplasia of epidermal epithelium, and a loss of cellular architectural organization of hte skin layers. The cellular changes in the epidermis are of particular concern because they may increase susceptibility to infection. Although many of the observed physiological insults resolved with a 21-day recovery period, the long-term biological effects of oil on sea turtles remain completely unknown.

Animals↗
PubMed1995

Upregulation of the GABAA/benzodiazepine receptor during anoxia in the freshwater turtle brain.

The freshwater turtle brain survives anoxia by decreasing its energy expenditure. During this anoxic period there is a sustained release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This study investigated whether there was a corresponding change in the binding properties of the GABAA/benzodiazepine (GABA/BDZ) receptor. Turtles (Trachemys scripta) were subjected to a 100% N2 atmosphere for up to 24 h. After exposure, the cerebral cortex was dissected out, and saturation binding assays for GABA/BDZ receptors were performed using the radioligand [3H]flunitrazepam. Control turtles had a dissociation constant (Kd) of 1.97 +/- 0.54 nM and a receptor density (Bmax) of 2,404 +/- 221 fmol/mg protein. The Kd showed no significant change over 24 h of anoxia. However, significant increases were seen in Bmax after 12 h (21%, P < 0.05) and 24 h (29%, P < 0.01) of anoxia. We suggest that a long-term upregulation of GABAA receptors occurs in the anoxic turtle brain that acts to increase the inhibitory effectiveness of the released GABA and thereby contributes to anoxia survival of the turtle.

Animals↗
PubMed1994

Regional changes in amino acid levels of the neonate rat brain during anoxia and recovery.

The aim of this study was to compare the changes in amino acids (alanine, aspartate, GABA, glutamate, glutamine, glycine, serine taurine) that are produced in different regions of the neonate brain (telencephalon, diencephalon cerebellum, brain stem) following a survivable period of anoxia and after the re-establishment of air respiration. Anoxia provoked different responses in the different regions. The changes during the anoxic period were as follows. In the brain stem there was a decrease in aspartate, in the telencephalon there was a significant increase in GABA and alanine and a decrease in aspartate, in the diencephalon, glutamate and GABA increased, and in the cerebellum, glycine and alanine levels were enhanced. The changes during recovery were even more dissimilar. Here the greatest shifts were seen in the brain stem with increases in glutamine, GABA, aspartate, glycine, serine, alanine, and taurine. In the telemcephalon glutamate fell and alanine increased, in the diencephalon GABA increased, and in the cerebellum, glutamate fell while glycine and alanine increased. In none of the major brain regions did the pattern of changes in neurotransmitters correspond to that seen in anoxic tolerant species.

Amino Acids↗
PubMed1994

Time course of anoxia-induced increase in cerebral blood flow rate in turtles: evidence for a role of adenosine.

The exceptional ability of the turtle brain to survive prolonged anoxia makes it a unique model for studying anoxic survival mechanisms. We have used epi-illumination microscopy to record blood flow rate in venules on the cortical surface of turtles (Trachemys scripta). During anoxia, blood flow rate increased 1.7 times after 45-75 min, whereupon it fell back, reaching preanoxic values after 115 min of anoxia. Topical superfusion with adenosine (50 microM) during normoxia caused a 3.8-fold increase in flow rate. Superfusing the brain with the adenosine receptor blocker aminophylline (250 microM) totally inhibited the effects of both adenosine and anoxia, while aminophylline had no effect on normoxic flow rate. None of the treatments affected systemic blood pressure. These results indicate an initial adenosine-mediated increase in cerebral blood flow rate during anoxia, probably representing an emergency response before deep metabolic depression sets in.

Adenosine↗
PubMed1993

Unchanged [3H]MK-801 binding and increased [3H]flunitrazepam binding in turtle forebrain during anoxia.

In order to determine if functional changes in N-methyl-D-aspartate receptors and GABAA receptors play a role in the remarkable anoxia tolerance of freshwater turtle brain, we used autoradiographic techniques to assay [3H]MK-801 and [3H]flunitrazepam binding in turtle forebrain after turtles had been subjected to anoxia for 2 or 6 h. The effects of glutamate, glycine, competitive N-methyl-D-aspartate antagonists, glycine antagonists, polyamines, magnesium, and zinc on [3H]MK-801 binding were the same in anoxic and control turtle forebrains. These results indicate that NMDA receptor regulation plays no role in the adaptive responses to anoxia in turtle brain. In contrast, [3H]flunitrazepam binding was significantly increased in the anoxic dorsal cortex and striatum. The most parsimonious explanation for elevated benzodiazepine receptor binding is that the rise in extracellular GABA levels known to accompany anoxia enhances benzodiazepine receptor affinity. It is possible, however, that GABAA receptor upregulation during anoxia increases the effectiveness of the inhibitory action of released GABA and contributes to the anoxia tolerance of turtles.

Animals↗