Anesthesia increases circulating glutamate in neurosurgical patients.

BACKGROUND: The excitotoxic amino acid glutamate is known to aggravate pre-existing neuropathology. Since volatile anesthetics increase plasma amino acid levels, we investigated if the anesthetics isoflurane and propofol increase plasma and cerebrospinal fluid (CSF) glutamate in neurosurgical patients. METHODS: In discectomized patients (n = 15), plasma glutamate was determined at 30 minute intervals before and during isoflurane anesthesia. In craniotomized patients (n = 66), plasma glutamate was assessed during and up to 24 hours after routine isoflurane or propofol anesthesia. CSF samples were withdrawn upon opening of the dura, before surgical manipulations. FINDINGS: During isoflurane anesthesia, plasma glutamate was significantly and reversibly increased in discectomized and craniotomized patients compared to healthy controls (56+/-6 microM; p<0.05), which was mostly sustained in male patients (males: 126+/-12 vs. females: 96+/-6 microM; p<0.05). With propofol, plasma glutamate was increased equally in men and women but to a lesser extent than with isoflurane (mean: 72+/-7 microM). CSF glutamate was significantly increased during isoflurane and propofol anesthesia compared to control lumbar CSF (1.2+/-0.1 microM; p<0.0001), being more prominent in patients with pre-existing brain edema receiving isoflurane (76+/-8 vs. propofol: 40+/-6 microM; p<0.05). CONCLUSIONS: The significant increases in plasma and CSF glutamate which were mostly sustained during isoflurane compared to propofol anesthesia should prompt the identification of anesthetic agents which do not impose a possible burden of glutamate-mediated excitotoxicity in patients with underlying compromised cerebral homeostasis. Detailed neuropsychological investigations following different anesthesia regimen are important to determine if transient elevations in CSF and plasma glutamate levels are of clinical relevance.

Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats.

BACKGROUND: Volatile anesthetics reduce neuronal excitation and cerebral metabolism but can also increase intracellular water accumulation in normal and injured brains. While attenuation of neuronal excitation and glutamate release are beneficial under pathological conditions, any increase in edema formation should be avoided. In the present study we investigated duration-dependent effects of the commonly used isoflurane/nitrous oxide (N2O) anesthesia on EEG activity, specific NMDA receptor binding, extracellular, CSF, and plasma glutamate, and cerebral water content in brain-injured rats subjected to short (30 minutes) or prolonged (4 hours) anesthesia. METHODS: Before controlled cortical impact injury (CCI), during prolonged (4-8 hours) or short anesthesia (7.5-8 hours after CCI), and before brain removal, changes in neuronal activity were determined by quantitative EEG analysis and glutamate was measured in arterial plasma. Brains were processed to determine acute and persisting changes in cerebral water content and 125I-Mk801 NMDA receptor binding at 8 and 32 hours after CCI, i.e., immediately or 24 hours after short or prolonged anesthesia. During prolonged anesthesia glutamate was measured via microdialysis within the cortical contusion. CSF was sampled before brain removal. FINDINGS: Prolonged isoflurane (1.8 vol%) anesthesia significantly increased EEG activity, plasma, cortical extracellular, and CSF glutamate, cortical and hippocampal 125I-Mk801 NMDA receptor binding, and cerebral water content in brain-injured rats. These changes were partially reversible within 24 hours after prolonged anesthesia. At 24 hours, CSF glutamate was significantly reduced following long isoflurane anesthesia compared to rats previously subjected to short anesthesia despite an earlier significant increase. Conclusions. The partially reversible increases in EEG activity, 125I-Mk801 NMDA receptor binding, cerebral water content, plasma and CSF glutamate appear important for physiological, pathophysiological, and pharmacological studies requiring prolonged anesthesia with isoflurane. Increases in extracellular cortical and plasma glutamate could contribute to acute aggravation of underlying tissue damage.

Isoflurane doubles plasma glutamate and increases posttraumatic brain edema.

Increased plasma and cerebral glutamate levels may contribute to posttraumatic edema formation. Since volatile anesthetics elevate plasma amino acid concentrations, the influence of isoflurane on arterial plasma glutamate levels and brain edema formation was investigated in brain-injured rats. Rats were anesthetized with chloral hydrate (380 mg/kg i.p.) or isoflurane (1.2-2.0 vol%) for four hours following controlled cortical impact injury. Isoflurane significantly increased arterial glutamate levels compared to chloral hydrate (124 +/- 12 vs. 60 +/- 5 microM; p < 0.005). At eight hours after trauma, water content was significantly increased in the traumatized hemisphere compared to the non-traumatized side (p < 0.005). In addition, four hours of isoflurane anesthesia caused a significant increase in brain water content of both hemispheres compared to chloral hydrate (80.1 +/- 0.1 vs. 79.6 +/- 0.1%; p < 0.005). Prolonged isoflurane anesthesia is associated with a significant increase in arterial plasma glutamate levels and brain water content. This increase in brain water content must be considered when performing prolonged isoflurane anesthesia.

Glutamate-containing parenteral nutrition doubles plasma glutamate: a risk factor in neurosurgical patients with blood-brain barrier damage?

OBJECTIVES: Animal studies have shown that the elevation of plasma glutamate levels increase cerebral edema formation whenever the blood-brain barrier is disturbed. Therefore, changes in plasma glutamate levels as influenced by the administration of a glutamate-containing amino acid solution were investigated in neurosurgical patients. DESIGN: Prospective, descriptive study. SETTING: Eight-bed neurosurgical intensive care unit in a university hospital. PATIENTS: Twenty-three neurosurgical patients requiring parenteral nutrition. INTERVENTIONS: Parenteral nutrition was begun 24 hrs after craniotomy. Patients receiving a glutamate-containing amino acid solution (3.75 g/L glutamate) were compared with patients infused with a glutamate-free solution. MEASUREMENTS AND MAIN RESULTS: Arterial plasma and urine amino acids were analyzed using high-performance liquid chromatography. Administration of a glutamate-containing solution doubled plasma glutamate levels in neurosurgical patients (from 53.3 +/- 9.8 microM [preinfusion] to 98.5 +/- 18.7 microM [after 4 hrs of infusion]; p < 0.001), whereas no elevation was seen when infusing a glutamate-free solution (from 52.3 +/- 7.3 [1 hr of infusion] to 53.6 +/- 6.4 microM [4 hrs of infusion]). Upon terminating the glutamate-containing infusion, arterial plasma glutamate levels decreased immediately (from 120 +/- 13.2 microM to 81.2 +/- 19.5 microM). Glutamate as infused in excess appears to exceed a renal threshold and is eliminated renally. CONCLUSIONS: As shown in animal models, administration of a glutamate-containing amino acid solution significantly increased plasma glutamate levels. Because such an increase in plasma glutamate levels could aggravate cerebral edema formation, glutamate-containing amino acid solutions cannot be recommended for patients with a disturbed blood-brain barrier.

Evaluation of absolute cerebral blood flow by laser-Doppler scanning-- comparison with hydrogen clearance.

A major limitation of laser-Doppler (LD) flowmetry, which enables noninvasive and continuous recording of tissue perfusion, is its inability to evaluate the absolute cerebral blood flow (CBF). Using a computer-controlled micromanipulator, the LD scanning technique provides information on the brain microcirculation in many different locations, information which is not available from a single stationary probe. The purpose of the current study was to examine whether LD scanning estimates can be calibrated for the absolute CBF by comparing LD scanning with the hydrogen clearance (HC) method. In Wistar rats (n = 31) including old rats (122-123 weeks old, n = 8), the CBF was altered using the global ischemia model by bilateral carotid artery occlusion coupled with hypobaric hypotension. The CBF was determined simultaneously by the LD scanning technique and HC at each mean arterial blood pressure step, and the correlation of CBF between the two techniques was analyzed. CBF measured by LD scanning was expressed as LD units. Absolute CBF values obtained by methods were correlated (r = 0.87), and the formula to calibrate absolute CBF values from LD units was y = 1.8x - 0.6. On the other hand, in old rats the formula to calibrate the absolute values was different (y = 1.3x + 8.3, r = 0.85). The results suggest that CBF data obtained by LD scanning could be calibrated into absolute blood flow values in particular circumstances, and that LD scanning could compensate in part for the weakness of LD flowmetry.

Glutamate and taurine are increased in ventricular cerebrospinal fluid of severely brain-injured patients.

Glutamate contributes to secondary brain damage, resulting in cell swelling and brain edema. Under in vitro conditions, increased extracellular levels of the amino acid taurine reflect glutamate-induced osmotic cell swelling. In vivo, increases in cerebrospinal fluid (CSF) taurine could, therefore, unmask glutamate-mediated cytotoxic edema formation and possibly differentiate it from vasogenic edema. To test this hypothesis, ventricular CSF glutamate and taurine levels were measured in 28 severely brain-injured patients on days 1, 5, and 14 after trauma. Posttraumatic changes in CSF amino acids were investigated in regard to extent of tissue damage and alterations in brain edema as estimated by computerized tomography. On day 1, CSF glutamate and taurine levels were significantly increased in patients with subdural or epidural hematomas (8+/-0.8/71+/-12 microM), contusions (21+/-4.1/122+/-18 microM), and generalized brain edema (13+/-3.2/80+/-15 microM) compared to lumbar control CSF (1.3+/-0.1/12+/-1 microM; p < 0.001). CSF amino acids, however, did not reflect edema formation and resolution as estimated by computerized tomography. CSF taurine correlated positively with glutamate, eventually depicting glutamate-induced cell swelling. However, parallel neuronal release of taurine with its inhibitory function cannot be excluded. Thus, the sensitivity of taurine in unmasking cytotoxic edema formation is weakened by the inability in defining its origin and function under the conditions chosen in the present study. Overall, persisting pathologic ventricular CSF glutamate and taurine levels are highly suggestive of ongoing glial and neuronal impairment in humans following severe traumatic brain injury.

Thiopental and midazolam do not seem to impede metabolism of glutamate in brain-injured patients.

Increased extracellular glutamate levels are related to glial and neuronal damage. Glutamate-mediated toxicity is limited by glial uptake and metabolic transformation of glutamate to glutamine and the energetic compounds alanine and lactate which are utilized by surrounding neurons. Under in vitro conditions, barbiturates have been shown to reduce glutamate uptake and its further metabolism, possibly impeding metabolic coupling between astrocytes and neurons. The aims were to investigate if under clinical conditions, the barbiturate thiopental reduces important detoxification of glutamate, resulting in lower CSF glutamine, alanine and lactate levels as opposed to patients receiving midazolam. During long-term administration of thiopental and midazolam, pathologically elevated ventricular CSF glutamate levels were associated with significantly increased glutamine and alanine levels up to 14 days after trauma. CSF lactate, however, remained normal. These data suggest that long-term administration of thiopental and midazolam under clinical conditions does not impede enzymatic activities responsible for detoxification and metabolism of glutamate.

A proton-translocating H+-ATPase is involved in C6 glial pH regulation.

Glial cells extrude acid equivalents to maintain pHi. Although four mechanisms have been described so far, pHi-control under physiological conditions is still not sufficiently explained. We therefore investigated whether a H+-translocating ATPase is involved in glial pHi homeostasis using an established glial cell line (C6 glioma). In the absence of bicarbonate, the inhibition of H+-ATPases by NEM led to a pHi decrease. The application of a more specific inhibitor (NBD-Cl) showed that the H+-ATPase involved is of the vacuolar type. Inhibition went along with delayed cell swelling. Together with the fact that glial acidification was far more pronounced in Na+-free media, this may serve as evidence for a secondary activation of Na+/H+-exchange once an activation setpoint is reached, which in turn causes secondary swelling from Na+-uptake. Stimulation of Na+/H+-exchange by PMA can increase the setpoint. pHi-recovery after an acid load was blocked by the inhibition of v-type H+-ATPase, if pHi did not reach 6.6 during the acid load. The inhibition of Na+/H+-exchange by amiloride inhibited recovery only if acidification was below the threshold. Finally, in bicarbonate-free media a v-type H+-ATPase contributes to pH-regulation in glial cells, especially during pH-homeostasis at physiological conditions, while Na+/H+-exchange gains significance during severe acid loads.

Microcirculation after cerebral venous occlusions as assessed by laser Doppler scanning.

Research on cerebral venous circulation disturbances (CVCDs) has been limited partly by the paucity of animal models that produce consistent venous infarction. Occlusion of two adjacent cortical veins in rats by means of a photochemical thrombotic technique provides a minimally invasive, clinically relevant, and reproducible model suited to study the pathophysiology of CVCDs. In this study, the effects of venous occlusion on regional cortical blood flow and the brain damage that ensues were evaluated. Cortical vein occlusion was induced by photoactivation of rose bengal via 100-microm fiberoptic illumination. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after venous occlusion, and regional cerebral blood flow (rCBF) was determined at 48 locations by using laser Doppler scanning. Histological damage was assessed 48 hours after vein occlusion. Occlusion of two cortical veins (Group T; seven animals) was compared with single-vein occlusion and its ensuing brain damage (Group S; five animals) and with sham-operated control (five animals). An rCBF reduction occurred 30 minutes after occlusion in Group T and was more extensive than the decrease in Group S after 60 minutes. Observation frequency histograms based on local CBF data obtained in Group T demonstrated that local CBF at some sites decreased to a level below the ischemic threshold within 90 minutes. Six of the seven rats in Group T had a growing venous thrombus with extravasation of fluorescein. The resulting infarction was significantly larger in Group T (9.8 +/- 4.5% of the hemispheric area) than in Group S (only 3 +/- 1.5% of the hemispheric area). In conclusion, microcirculation perturbations occur early after venous occlusion and result in the formation of a venous thrombus accompanied by local ischemia and severe venous infarction. The extent of vein occlusion determines the resulting brain damage. Based on the results of this study, the authors conclude that CVCDs may be attenuated by prevention of venous thrombus progression together with the use of protective measures against the consequences of ischemia.

Inhibition of lactate export by quercetin acidifies rat glial cells in vitro.

The relationship between glial lactate release and glial intracellular pH (pHi) regulation is studied using C6 glioma cells and rat astrocytes in vitro, and the lactate transport inhibitors quercetin and alpha-cyano-4-hydroxycinnamate (CHC). pHi is measured using 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The results show that lactate release is mediated partly by a specific lactate transport system inhibitable by quercetin (50 microM), but not by CHC (5 mM). Inhibition by quercetin results in a significant 3-4-fold increase of intracellular lactate and a decrease of intracellular pH to 6.9. A participation of quercetin-inhibitable lactate transport in glial pHi-regulation is suggested by the observation that pHi-homeostasis after acidification by diffusion of undissociated lactic acid into the cell is inhibited by quercetin. The existence of a system controlling lactate release in glial cells may also reflect a function of astrocytes to supply neurons with lactate.

Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases.

Glutamate-mediated excitotoxicity is associated with adenosine triphosphate (ATP) degradation and generation of oxygen radicals. Hypoxanthine and lactate depict energetic impairment, while xanthine and uric acid reflect activity of radical producing xanthine oxidase. Cerebrospinal fluid (CSF) glutamate, hypoxanthine, lactate, xanthine, and uric acid were investigated in neurological patients. In multiple sclerosis, myelopathy, stroke, epilepsy and viral meningitis glutamate, hypoxanthine, xanthine, and uric acid are increased 2-3-fold compared to controls. Lactate is only elevated in meningitis. Normal lactate dehydrogenase (LDH) levels and absent correlation between the albumin ratio and neurochemical parameters exclude an artificial increase due to cell lysis and barrier damage. Absent correlation between neurochemical parameters within each patient group is most likely related to preserved glial and neuronal uptake mechanisms. CSF hypoxanthine, xanthine, and uric acid levels appear superior to lactate in reflecting glutamate-mediated excitotoxicity in neurological patients.

Neurotransmitters in cerebrospinal fluid reflect pathological activity.

The excitatory transmitters glutamate and aspartate become toxic whenever their extracellular levels are increased because of neuronal, glial and endothelial impairment. Taurine, a volume-regulating amino acid, is released upon excitotoxin-induced cell swelling. Our aim was to investigate if glutamate and aspartate in cerebrospinal fluid (CSF) reveal neuropathology in neurological patients, and if taurine unmasks glutamate-mediated toxicity. Glutamate and aspartate are doubled in viral meningitis, acute multiple sclerosis (MS) and myelopathy compared with control subjects and patients with peripheral facial nerve palsy. These levels do not coincide with a disturbed blood-brain barrier, as estimated by the albumin ratio, are independent of their precursors (glutamine, asparagine) and are not associated with cell lysis. Taurine is significantly increased in meningitis, acute MS, and myelopathy, suggesting glutamate-mediated toxicity. Analysis of transmitters in lumbar CSF can be used to identify patients with cerebral and spinal pathology who might benefit from specific receptor-modulating agents.

Cerebral protection against ischemia by locomotor activity in gerbils. Underlying mechanisms.

BACKGROUND AND PURPOSE: A previous communication of this laboratory demonstrated reduced mortality and neuronal damage by spontaneous locomotor activity preceding forebrain ischemia in Mongolian gerbils. The present experiments seek to elucidate potential mechanisms of protection by measurement of cerebral blood flow, cerebral tissue conductance as an indicator of ischemic cell swelling, and the cerebral release of eicosanoids. METHODS: Gerbils were maintained either in conventional cages (nonrunners) or with free access to running wheels (runners) for 2 weeks preceding 15 minutes of forebrain ischemia. During ischemia and 2.5 hours of reperfusion, cerebral tissue conductance was determined with a two-electrode system. Simultaneously, prostaglandin D2, prostaglandin F2 alpha, and thromboxane B2 were measured in ventriculocisternal perfusate. In additional animals cerebral blood flow was assessed by hydrogen clearance. RESULTS: Decreases in tissue conductance during ischemia were similar in nonrunners (56 +/- 3%) and runners (62 +/- 3%) but normalized more rapidly in runners during reperfusion. In both groups reperfusion was accompanied by marked increases of perfusate prostaglandin D2, prostaglandin F2 alpha, and thromboxane B2. In nonrunners, however, thromboxane B2 was already elevated during ischemia (147 +/- 9%, P < .01) and remained elevated longer during recirculation (P < .05). Postischemic perfusion maxima were higher in runners (70.8 +/- 7.4 versus 47.0 +/- 5.0 mL/100 g per minute, P < .05) and were observed sooner (27.4 +/- 6.9 versus 62.2 +/- 12.3 minutes, P < .05). Both groups displayed delayed hypoperfusion of a similar magnitude (runners, 29.0 +/- 2.4 mL/100 g per minute; nonrunners, 30.1 +/- 2.4 mL/100 g per minute). CONCLUSIONS: Protection by preischemic locomotor activity may involve enhanced postischemic reperfusion, leading to more rapid normalization of conductance and thus of cell volume. Enhanced reperfusion may be the consequence of attenuated thromboxane liberation during and after ischemia.

Unspecific metabolic blood parameters as used in clinical routine may differentiate malignant from benign cerebral tumors.

The investigation of rather insensitive metabolic parameters (protein, fibrinogen, blood urea nitrogen (BUN), blood glucose) reveals significant differences between tumor-bearing and tumor-free patients as well as benign and malignant neoplasms. Whereas metastases and glioblastomas (GBM) show significantly elevated BUN levels (21.9 +/- 1.7; 8 +/- 2.2 mg/dl) compared to benign tumors (meningioma WHO I, astrocytoma I, II) (16 +/- 0.9 mg/dl) and tumor-free matched controls (e.g. 13.9 +/- 1.4 mg/dl) only metastases depict higher glucose (141.7 +/- 11mg/dl) counts. Fibrinogen, significantly elevated in malignancy (395 +/- 25.2; 397.2 +/- 25.9 mg/dl) is without difference between meningioma, astrocytoma (253.2 +/- 16.6; 271.5 +/- 16.5 mg/dl) and controls (e.g. 270.1 +/- 10.8 mg/dl). Correlating BUN with total protein reveals a metabolic mismatch to nearly all tumor patients, regardless of dignity, as compared to tumor-free patients. Neuroendocrinoimmunological changes are the most likely reason for these overt as well as occult findings, making investigation of more sensitive metabolic parameters a rewarding task.

Correlation of cerebral blood flow and MCA flow velocity measured in healthy volunteers during acetazolamide and CO2 stimulation.

The assessment of the cerebrovascular reserve capacity (RC) has become a widely used tool in the management of cerebrovascular disease. Discrepancies become obvious, however, if results obtained with different methods are compared. Aim of the present study, therefore, was to compare blood velocity and cerebral perfusion data in the same group of healthy test persons. In 32 volunteers regional cerebral blood flow (rCBF) was measured with the 133Xe-inhalation method. F1 as grey matter flow and the initial slope index (ISI) were computed. Simultaneously flow velocity in the middle cerebral artery (VMCA) was assessed by transcranial Doppler sonography (TCD). Measurements were performed in the resting state, during inhalation of 7% CO2 and after 1 g acetazolamide. Baseline VMCA was 62.38 +/- 16.1 cm/s, 90.84 +/- 23.85 cm/s during hypercapnia and 84.91 +/- 24.54 cm/s after acetazolamide. There was no significant change of baseline or stimulated values with age. F1 rose from baseline 76.25 +/- 12.48 ml/100 g/min to 103.90 +/- 14.6 ml/100 g/min in hypercapnia and to 98.4 +/- 14.9 ml/100 g/min after acetazolamide. The baseline F1 values and the response to CO2 decreased with age (p = 0.01) whereas for the acetazolamide reaction an age dependency could not be proven. ISI baseline values (41.5 +/- 6.1 ml/100 g/min) as well as those found after CO2 or acetazolamide decreased significantly with age. In hypercapnia changes of F1 and ISI were not too well related with changes of VMCA (F1: r = 0.599; ISI: r = 0.473), but better during acetazolamide exposure (F1: r4 = 0.715; ISI: r = 0.522). The age dependency of resting and stimulated values has to be considered when assessing the reserve capacity. There is a correlation between changes of the perfusion and flow parameters in healthy individuals which, however, may be worse in cerebrovascular disease.

Transcranial Doppler and cortical microcirculation at increased intracranial pressure and during the Cushing response: an experimental study on rabbits.

The effect of increased intracranial pressure on the flow velocity of the basilar artery was measured with transcranial ultrasonic Doppler in New Zealand White rabbits under alpha-chloralose anesthesia and artificial respiration. Laser Doppler flowmetry served to study changes of the cortical microcirculation. The results confirm a high inverse correlation of the diastolic flow velocity, the pulsatility index, and the resistance index with the cerebral perfusion pressure (CPP). During acute intracranial hypertension, however, these parameters do not show a good correlation with the local cortical blood flow. The absence of a correlation was evident over a wide CPP range down to values of 35 mm Hg. Only at CPP values below this critical threshold is the microcirculation impaired. The threshold is reached at pulsatility index values of more than 2.0 and at resistance index values of more than 0.8. Therefore, transcranial Doppler indices permit the detection of critical reductions of microcirculatory blood flow. The Cushing reaction occurred with a constant time lag of 5.5 +/- 0.7 seconds after the loss of CPP. The Cushing reaction did not establish systolic blood flow, which remained below the functional threshold, as concluded from the temporary loss of somatosensory evoked potentials.

[Neuroprotection. Models and basic principles]. / Neuroprotektion. Modelle und Grundprinzipien.

This review describes recently recognized pathophysiologic mechanisms responsible for brain damage during ischemia and reperfusion and new therapeutic concepts developed on a rational basis. Mediators of secondary damage include excitotoxins such as glutamate, acidosis, free radicals, and the disturbance of the microcirculation seen in the early phase of recirculation. Glutamate is an excitatory neurotransmitter, which may turn neurotoxic when the energy supply is limited. Tissue acidosis down to pH 6.0 develops regularly in cerebral ischemia and disturbs a variety of neuronal functions, causing glial swelling and neuronal death. Free radicals attack brain lipids, the cell membrane and myelin in particular, and are produced during reperfusion. Disturbance of the microcirculation aggravates ischemic damage. Suggested therapeutic approaches include glutamate antagonists, normalization of tissue acidosis, and use of new diuretics to reduce glial swelling, protection of the brain by free radical scavengers such as 21-aminosteroids, tocopherol, allopurinol or superoxide dismutase, and hypothermia. Ways of ensuring fast reperfusion, including hypervolemic hemodilution and blood pressure stabilization, are suggested for resuscitation or early stroke. All data available indicate that the combination of several successful therapeutic principles will significantly improve outcome.

Cerebral blood flow autoregulation during hypobaric hypotension assessed by laser Doppler scanning.

Hypobaric hypotension was used to reduce systemic blood pressure in rats below the lower threshold of CBF autoregulation to evaluate a new laser Doppler (LD) "scanning" technique. Spontaneously breathing male Wistar Kyoto rats (n = 8) were anesthetized with chloral hydrate and the head fixed in a stereotaxic head holder. A cranial window with intact dura mater was introduced to assess local CBF (lCBF) by LD. One stationary probe served to detect rapid flow changes, whereas the second probe was used to sample lCBF recordings from many cortical locations by means of a stepping motor-controlled micromanipulator to obtain lCBF frequency histograms. Advantages are an improved spatial resolution together with the easy detection of low-flow areas and a better comparison of data from individual experiments. Arterial blood pressure was stepwise reduced by exposing the lower body portions to subatmospheric pressures (hypobaric hypotension), thus avoiding the use of drugs or heparinization. The lower threshold of CBF autoregulation was detected by "scanning" at arterial pressures between 50 and 46 mm Hg, with low-flow spots occurring immediately. The data suggest LD scanning as a method suited particularly for studies where lCBF inhomogeneities are expected, e.g., the ischemic penumbra or sinus vein thrombosis.

Neuron-glial interaction during injury and edema of the CNS.

During injury and ischemia of the CNS mediator compounds are released or activated which cause secondary swelling and damage of nerve cells. Such mediators are glutamate, acidosis, free fatty acids, or high extracellular potassium. Glial homeostatic mechanisms are activated to prevent the secondary injury from these mediators. The glial clearance mechanisms have been studied in detail using in vitro systems allowing for a close control of the glial environment. Current evidence suggests glial swelling to occur together with glutamate uptake or in response to extracellular acidosis. Glial swelling, therefore, is rather the result of homeostatic mechanisms than an indication of glial demise.