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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental models of focal cerebral ischemia have provided important data on early circulatory and biochemical changes, but typically their correspondence with metabolic and hemodynamic findings in stroke patients has been poor. To fill the gap between experimental studies at early time points and rather late clinical studies, we repeatedly measured CBF, CMRO2, oxygen extraction fraction (OEF), cerebral blood volume (CBV), and CMRglc in six cats before and up to 24 h after permanent middle cerebral artery (MCA) occlusion (MCAO), using the 15O steady state and [18F]fluorodeoxy-glucose methods and a high-resolution positron emission tomography (PET) scanner. Likewise, three sham-operated control cats were studied during the same period. Final infarct size was determined on serial histologic sections. In the areas of final glucose metabolic depression that were slightly larger than the histologic infarcts, mean CBF dropped to approximately 40% of control values immediately on arterial occlusion. If further decreased to < 20% during the course of the experiment. This progressive ischemia was most conspicuous in border zones. CMRO2 fell to a lesser degree (55%), eventually reaching approximately 25% of its control level. At early stages, OEF increased mainly in the center of ischemia. With time, areas of increased OEF moved from the center to the periphery of the MCA territory. Concurrently, progressive secondary decreases in OEF in conjunction with further reductions of CBF and CMRO2 indicated the development of central necrosis. The findings are highly suggestive of a dynamic penumbra. In five cats with complete MCA infarcts, CBF decreased and OEF increased in the contralateral hemisphere after 24 h, suggesting whole-brain damage. This effect may be explained by the widespread brain edema found histologically in addition to the nonspecific CBF reductions and OEF elevations observed also in the sham-operated controls after 1 day in the experimental condition. In one cat, cortical OEF increased only transiently. Normal CMRO2 and CMRglc were eventually restored, and the final infarct was small. This study demonstrates that acute regional pathophysiologic changes can be repeatedly assessed by multivariate PET in cats. Viable tissue can be detected up to several hours after MCA occlusion, and the transition of misery-perfused regions into necrosis or preserved tissue can be followed over time. The present results support the concept of a dynamic penumbra, in which for up to 24 h tissue damage spreads progressively from the center to the periphery of ischemia. Sequential high-resolution PET provides insight into the dynamics of regional pathophysiology and may thus further the development of rational therapeutic strategies.
J Cereb Blood Flow Metab 1994 Nov
PMID:Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats. 792 54

Intracellular bioenergetic state and extracellular adenosine levels were monitored in rat brain prior to and following traumatic brain injury (TBI) using phosphorus magnetic resonance spectroscopy and microdialysis, respectively. Fluid percussion-induced TBI (2.6 +/- 0.2 atm) resulted in significant reductions in free cytosolic [Mg2+], cytosolic [ATP]/[ADP] [P(i)], and delta GATP and elevations in cytosolic [ADP] and [5'-AMP]. Intracellular ATP concentration and pH did not change significantly after trauma. Mitochondrial capacity for oxidative phosphorylation (indexed by V/Vmax) increased significantly from approximately 0.45 prior to injury to approximately 0.58 following TBI. All metabolic changes were maximal at 2-3 h post-TBI. Conversely, extracellular adenosine concentrations increased transiently following TBI, with levels peaking at 10 min posttrauma, then declining rapidly to preinjury values by 50 min. Thus, despite pronounced long-term depression in bioenergetic status and a marked rise in [5'-AMP], formation and release of adenosine were elevated only transiently within the first hour following TBI. Since steady-state adenosine levels were essentially unchanged beyond 1 h posttrauma, mooted neuroprotective actions of endogenous adenosine would be minimized. Intracerebroventricular injections of 2-chloroadenosine (0.5 and 2.5 nmol) immediately prior to TBI dose-dependently attenuated metabolic disturbances and improved posttraumatic neurologic outcome (p < 0.05). The observations indicate that (a) TBI results in dissociation of adenosine release from intracellular bioenergetic state, a phenomenon possibly contributing to secondary injury following TBI; and (b) supplementing brain with an adenosine agonist attenuates irreversible injury.
J Cereb Blood Flow Metab 1994 Sep
PMID:Dissociation of adenosine levels from bioenergetic state in experimental brain trauma: potential role in secondary injury. 806 80

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.
J Cereb Blood Flow Metab 1994 Sep
PMID:Time course of anoxia-induced increase in cerebral blood flow rate in turtles: evidence for a role of adenosine. 806 83

In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological importance for determining the volume of the ischemic infarct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals. Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 +/- 14% of control (mean +/- SD; p < 0.05), tissue PO2 declined from 28 +/- 4 to 21 +/- 3 mm Hg (p < 0.05), and EEG power fell to approximately 80% of control. During 7-h occlusion, 3-11 DC deflections with a mean duration of 5.2 +/- 4.8 min occurred at irregular intervals, and EEG power gradually declined to 66 +/- 16% of control (p < 0.05). During the passage of DC deflections, LDF did not change, but PO2 further declined to 19 +/- 4 mm Hg (p < 0.05). KCl-induced depolarizations of intact rats were significantly shorter (1.4 +/- 0.5 min; p < 0.05) and were accompanied by a 43% increase in LDF (p < 0.05) and a slight but significant increase in tissue PO2 from 22 +/- 4 to 25 +/- 4 mm Hg (p < 0.05). The comparison of periinfarct and KCl-induced depolarizations demonstrates that oxygen requirements are not coupled to an appropriate flow response in the periinfarct zone with severely reduced blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1994 Jan
PMID:Cortical negative DC deflections following middle cerebral artery occlusion and KCl-induced spreading depression: effect on blood flow, tissue oxygenation, and electroencephalogram. 826 47

The purposes of this study were to determine whether cortical spreading depression occurs outside of the infarct produced by photothrombotic vascular occlusion, and also the direction of spreading. Focal cerebral thrombotic infarction was produced by irradiating the exposed skull of anesthetized rats with green light (560 nm) following systemic injection of rose bengal dye. At proximal sites (approximately 2 mm anterior to the infarct border), transient, severe hyperemic episodes (THEs) lasting 1-2 min were intermittently recorded. THE frequency was greatest in the first hour and declined over a 3-h period. THEs were accompanied (and usually preceded) by a precipitous rise in [K+]0 (from approximately 3 to > 40 mM) and were associated with increases in local tissue oxygen tension (tPO2). Following the rise in [K+]0, clearance of [K+]0 to its pre-THE baseline preceded baseline recovery of CBF. These data indicate that THEs were reactive to physiologic events resembling cortical spreading depression (CSD), which provoked increased demand for oxygen and blood flow, and which spread from proximal sites to areas more distal (approximately 4 mm) from the rim of the evolving infarct. MK-801 (1 mg/kg, i.v.) inhibited subsequent CSD-like episodes. We conclude that photothrombosis-induced ischemia provoked CSD which was triggered either within the infarct core or in the infarct rim and spread to more distal sites. Whether multiple episodes of CSD during infarct generation are responsible for the remote consequences of focal brain injury remains to be determined.
J Cereb Blood Flow Metab 1994 Jan
PMID:Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions. 826 54

Gradient echo magnetic resonance (MR) imaging was used to demonstrate propagating waves of cortical spreading depression (SD) in the anaesthetised rat. SD was initiated by remote perfusion with 150 mM KCl applied for 0.5-2 min to the left parietal cortex. Gradient echo MR images were obtained every 12-30 s in either a vertical coronal section or a horizontal section including the superficial cortex in plan view. Within 2 min of application of KCl, we observed a zone of increased signal intensity (3-15%) on the MR image, up to 2 mm across, lasting approximately 1 min and propagating away from the site of initiation. The mean velocity for 27 of such waves seen in seven animals was calculated to be 2.79 mm/min, with means (+/- SD) in individual animals averaging 2.90 +/- 0.46 mm/min (n = 7). Increased signal intensity in gradient echo images has been attributed to an increased level of oxygenation within the venous blood. Our results are consistent with this interpretation although other physiological changes during SD may also contribute to the signal changes.
J Cereb Blood Flow Metab 1994 Jan
PMID:Magnetic resonance imaging of propagating waves of spreading depression in the anaesthetised rat. 826 59

Cortical tissue surrounding acute ischemic infarcts undergoes repetitive spontaneous depolarizations. It is unknown whether these events are episodes of spreading depression (SD) elicited by the elevated interstitial K+ ([K+]e) in the ischemic core or whether they are evoked by transient decreases of the local blood flow. Electrophysiologically, depolarization caused by SD or by ischemia (ID) can be distinguished by their characteristic patterns of [K+]e rise: During SD, [K+]e rises abruptly, while in ID, this fast rate of increase is preceded by a slow rate lasting minutes. To characterize the depolarizations, we occluded the right middle cerebral artery (MCA) in rats and inserted two K(+)-sensitive microelectrodes into the cortex surrounding the evolving infarct. Repeated increases in [K+]e arose spontaneously following MCA occlusion. [K+]e increased during these transients from a resting level of 3-6 to 60 mM. One-third of these transient increases in [K+]e were biphasic, consisting of a slow initial increase to 10-12 mM, which lasted for minutes, followed by an abrupt increase, a pattern characteristic of ID. The remaining two-thirds exhibited a steep monotonic increase in [K+]e (< 10 s), characteristic of SD. The duration of the transients was a function of the pattern of [K+]e increase: ID-like transients lasted an average 10.7 +/- 5.1 min, whereas the duration of SD-like transients was 5.7 +/- 3.4 min. Both types of K+ transients occurred in an apparently random fashion in individual animals. A K+ transient was never observed solely at one electrode.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1993 Jul
PMID:Characterization of cortical depolarizations evoked in focal cerebral ischemia. 831 12

The objective of this study was to establish whether tissues that are energy compromised, but not energy depleted, demonstrate exaggerated calcium transients when subjected to membrane depolarizations of the spreading depression (SD) type. Anesthetized and artificially ventilated rats were given insulin in order to induce progressively lower plasma glucose concentrations. Spreading depression was elicited by local application of KCl; extracellular calcium concentration (Ca2+e) as well as direct current (DC) potential were recorded. When plasma glucose concentration fell below approximately 3 mM, the duration of the Ca2+e transient gradually increased to values exceeding 500% of control. The increase was associated with a corresponding increase in the duration of the DC potential shift, but the amplitude of the Ca2+e transient did not change. It is concluded that a restriction of glucose (or oxygen) supply, as occurs in hypoglycemia (or hypoxia), prolongs the calcium transient associated with depolarization of the SD type, even though tissue phosphocreatinine and ATP concentrations are normal. The results support the contention that repeated depolarizations, occurring in the penumbral zone of a focal ischemic lesion, could lead to calcium-related damage.
J Cereb Blood Flow Metab 1993 Jan
PMID:Influence of plasma glucose concentration on rat brain extracellular calcium transients during spreading depression. 841 7

Brain trauma is associated with acute functional impairment and neuronal injury. At present, it is unclear to what extent disturbances in ion homeostasis are involved in these changes. We used ion-selective microelectrodes to register interstitial potassium ([K+]e) and calcium ([Ca2+]e) concentrations in the brain cortex following cerebral compression contusion in the rat. The trauma was produced by dropping a 21 g weight from a height of 35 cm onto a piston that compressed the cortex 1.5 mm. Ion measurements were made in two different locations of the contused region: in the perimeter, i.e., the shear stress zone (region A), and in the center (region B). The trauma resulted in an immediate increase in [K+]e from a control level of 3 mM to a level > 60 mM in both regions, and a concomitant negative shift in DC potential. In both regions, there was a simultaneous, dramatic decrease in [Ca2+]e from a baseline of 1.1 mM to 0.3-0.1 mM. Interstitial [K+] and the DC potential normalized within 3 min after trauma. In region B, [Ca2+]e recovered to near control levels within 5 min after ictus. In region A, however, recovery of [Ca2+]e was significantly slower, with a return to near baseline values within 50 min after trauma. The prolonged lowering of [Ca2+]e in region A was associated with an inability to propagate cortical spreading depression, suggesting a profound functional disturbance. Histologic evaluation 72 h after trauma revealed that neuronal injury was confined exclusively to region A. The results indicate that compression contusion trauma produces a transient membrane depolarization associated with a pronounced cellular release of K+ and a massive Ca2+ entry into the intracellular compartment. We suggest that the acute functional impairment and the subsequent neuronal injury in region A is caused by the prolonged disturbance of cellular calcium homeostasis mediated by leaky membranes exposed to shear stress.
J Cereb Blood Flow Metab 1993 Mar
PMID:Regional changes in interstitial K+ and Ca2+ levels following cortical compression contusion trauma in rats. 843 9

Proximate neurotoxic mechanisms during postischemic recovery may be influenced by stage of development and complicating factors such as cortical spreading depression or secondary brain insult. Using 31P nuclear magnetic resonance spectroscopy, we have monitored pH and cellular energy metabolites phosphocreatine (PCr) and ATP in the ex vivo rat cerebral cortex before, during, and after substrate and oxygen deprivation, which represents "in vitro ischemia." There were important developmental differences in resistance and response to an ischemic insult. Twenty-one-day-old (P21) rat cortical slices had no detectable beta-ATP or PCr at the end of a 20-min insult, while 7-day-old (P7) slices had 50 +/- 13.7% (mean +/- SD, n = 12) and 17 +/- 14.8% relative to preischemia levels, respectively. Postischemic depolarization resulted in age-dependent effects on PCr (p < 0.05): In the older tissue, depolarization significantly worsened the recovery of PCr, whereas in young tissue it ameliorated recovery. This amelioration could be prevented by inhibiting nitric oxide production with methylene blue (depolarization-methylene blue interaction, p < 0.05) and enhanced by administration of the nitric oxide donor glyceryl trinitrate (GTN; p < 0.01). However, in P21 tissue, GTN further exacerbated injury (age-GTN interaction, p < 0.01). Therefore, in this vascular-independent preparation, a neuronal or glial nitric oxide-dependent mechanism appears to confer improved postischemic bioenergetic recovery in the developing brain compared with the mature brain.
J Cereb Blood Flow Metab 1996 Jan
PMID:Bioenergetic recovery following ischemia in brain slices studied by 31P-NMR spectroscopy: differential age effect of depolarization mediated by endogenous nitric oxide. 853 May 45


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