Granular cell tumor of the fifth cranial nerve: further evidence for Schwann cell origin.

Granular cell tumors arising from the cranial nerves are rare. We describe a granular cell neoplasm of the fifth cranial nerve in a 66-year-old male. Light microscopic appearances included rows and clusters of cells with small peripheral nuclei and abundant eosinophilic cytoplasm. Ultrastructurally the cytoplasm of these cells contained numerous dense bodies, multivesicular bodies and vacuoles. In some areas tumor cells were intermingled with myelinated and unmyelinated nerve fibers showing the same relationships as do Schwann cells and nerve fibers. The association between tumor cells and axon seen in this case lends further support to the putative Schwann cell origin of this neoplasm.

Extracellular pH, potassium, and calcium activities in progressive ischaemia of rat cortex.

We measured the relationships between changes in extracellular pH (pHe), potassium (Ke), and calcium (Cae) activities and DC potential (DCe) in progressive ischaemia of rat cerebral cortex. pHe and Ke, or Cae and Ke, were measured at the same point simultaneously, using triple-barrelled, double-ion-sensitive microelectrodes. Ischaemia was produced using bilateral carotid artery occlusion and hypotension in rats under 50% N2O-0.4% halothane anaesthesia. Unilateral carotid artery occlusion did not affect blood flow, but bilateral occlusion reduced flow to approximately 40% of normal. Autoregulation of blood pressure (BP) changes was lost after bilateral occlusion, and so progressive hypotension produced a linear decrease in flow. pHe began to decrease at high levels of flow (30-35 ml 100 g-1 min-1) and showed stepwise acidotic shifts with reductions in BP. Ke was affected at flows of approximately 15 ml 100 g-1 min-1, during which time it was critically dependent on BP. When Ke reached 6 mM, it increased rapidly to 40 mM and was associated with a negative shift in DCe. When Ke reached approximately 10 mM, Cae decreased rapidly to approximately 0.1 mM. pHe had reached 6.87 when Ke increased rapidly and showed a transient alkalotic shift of approximately 0.14 units at that time. Possible mechanisms for the sequence of ion changes described are discussed.

Simple staining for heat-fixed brain sections after topographical pH analysis or autoradiographic studies.

Powerful topographic techniques are now available, among which autoradiographic and fluorescent mapping are the most prevalent. These techniques produce images that usually do not correlate with brain anatomy; subsequent staining is required to allow a precise association between the parameter(s) investigated and brain structures. A simple staining procedure is described, compatible with heat-fixed brain sections, and that was found particularly valuable in association with topographical tissue pH studies using the fluorescent pH indicator umbelliferone.

Changes in extracellular calcium activity in cerebral ischaemia.

Changes in extracellular ion activities were measured during partial ischaemia of the cerebral cortex of primates anaesthetized with alpha-chloralose. Triple-barrelled, double-ion-sensitive microelectrodes were used to measure the extracellular potassium (Kc) and calcium (Cac) activity at the same point simultaneously. The ion changes were related to local cerebral blood flow, and it was shown that at a blood flow of approximately 10 ml 100 g-1 min-1, there is a threshold below which ion homeostasis is disturbed. This is associated with a dramatic rise in Ke and fall in Cae. Cae falls from a normal value of 1.31 +/- 0.1 mM to approximately 0.28 mM in densely ischaemic tissue. In ischaemia, Ke reaches 13.4 +/- 3.8 mM before Cae begins to fall. The fall in Cae, although related to reduced blood flow, is closely associated with and follows the rise in Ke. The change in Cae is probably due to an increase in membrane permeability, as a result of either depolarisation or a critical lowering of cellular energy reserves.

Comparison of the effects of ischaemia on early components of the somatosensory evoked potential in brainstem, thalamus, and cerebral cortex.

In 14 ventilated, normocapnic baboons anaesthetised with alpha-chloralose, local CBF (hydrogen clearance) and the amplitude and latency of local components of the somatosensory evoked potential (SEP, median nerve stimulation) were measured bilaterally in ventrobasal thalamus (VPL), medial lemniscus (ML), and cerebral cortex before and during progressive ischaemia, produced by occlusion of the right middle cerebral artery and subsequent controlled reductions in mean systemic blood pressure (MSBP). The first significant reduction from control of the left cortical SEP amplitude occurred in the range of 30-40 mm Hg MSBP, but those of the VPL and ML responses only below 30 mm Hg; in the range of 20-30 mm Hg, the average SEP amplitudes in cortex, VPL, and ML were 8.6, 72.6, and 90.7% of control, respectively. In terms of local CBF, the cortical SEP threshold was in the range of 15-20 ml/100 g/min (as in previous work), that of VPL in the range of 10-15 ml/100 g/min, but the ML response was only markedly reduced below 10 ml/100 g/min. Thus, the differential ischaemic sensitivity of the SEP between the three regions was clearly demonstrated. These results indicate that as one descends the neuraxis, there is an increasing resistance of electrophysiological function to systemic hypotension, together with a decreasing threshold for local ischaemia.

Cerebral extracellular calcium activity in severe hypoglycemia: relation to extracellular potassium and energy state.

The changes in extracellular Ca2+ (Cae) and K+ (Ke) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N2O anaesthesia), there was an increase in Ke which, at approximately 13 mM, was associated with a fall in Cae. Ke peaked at 48 +/- 12 mM, and Cae at 0.18 +/- 0.28 mM. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Cae recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity , but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.

In situ freezing of the brain for metabolic studies: evaluation of the "box" method for large experimental animals.

The box method of freezing the brain in situ was assessed in baboons. The cooling rate of the tissue was monitored in several regions located at various depths from the skull surface. These measurements allowed us to examine the time required for the tissue to reach 0 degree C, in relation to its depth measured from the top of the skull. To define brain regions with proven ischaemia, frozen tissue sections were surveyed for areas of decreased pH. In addition, concentrations of ATP, phosphocreatine, and lactate were determined in gray matter located at various depths from the top of the brain surface. Normal tissue pH and low lactate concentration, without any significant decrease in high-energy phosphate levels, were found in regions at a depth less than approximately 10 mm from the brain surface. Deep structures including the inferiomedial aspect of the temporal lobe, the lateral geniculate body, and the limbic system (hippocampus) consistently showed mild tissue acidosis, indicating that these regions were subjected to some degree of ischaemia before they were reached by the freezing front. In some cases, acidosis was also detectable in the thalamus, basal ganglia, and in the deeper part of some sulci. We conclude that, with baboons, in situ freezing using the box method is valid for metabolic studies of the cerebral cortex and structures located at a depth less than approximately 10 mm from the top of the brain surface.

pH, K+, and PO2 of the extracellular space during ischaemia of primate cerebral cortex.

pH and K+ from the extracellular space, PO2, and CBF have been measured in the same region during progressive ischaemia of primate cerebral cortex. As blood flow was reduced, the other changes had the following sequence. PO2 fell rapidly to 30% of control levels at regional CBF (rCBF) of 30 ml 100 g-1 min-1. As CBF was further reduced, PO2 continued to fall. pH remained stable until around 20 ml 100 g-1 min-1, below which pH fell rapidly, with an exponential increase in H+ concentration. K+ showed the well-known relationship to CBF, remaining normal until around 10 ml 100 g-1 min-1, below which K+ rose rapidly. pHe and log K+ were lin-early related and confirmed that pH fell by 0.3 U before K+ rose significantly, and fell by 0.6 U before the massive rise in K+. The mechanisms involved in this sequence of events and the role of pH changes in the development of the so-called "ischaemic penumbra" are discussed.

Brain tissue concentrations of ATP, phosphocreatine, lactate, and tissue pH in relation to reduced cerebral blood flow following experimental acute middle cerebral artery occlusion.

Local CBF (LCBF) was compared with the corresponding local tissue concentration of ATP, phosphocreatine (PCr), and lactate in anaesthetized baboons subjected to focal ischaemia produced by middle cerebral artery occlusion (MCAO). LCBF hydrogen electrodes were implanted in cortical regions where MCAO had been previously shown to produce severe and penumbral ischaemia and in posterior regions where blood flow is not altered. Metabolites were assayed in small tissue samples collected either by cryoprobe biopsy in the regions where LCBFs were measured (series 1) or by sampling appropriate regions of the rapidly frozen brain (series 2). Subsequent topographical study of brain tissue pH with umbelliferone was performed in this latter series. The results from these two series are compared and discussed in terms of the more appropriate way to perform simultaneous electrode measurements and analysis of tissue samples for studying focal ischaemia in the primate brain. They confirm that the concentrations of ATP and PCr decrease, and that lactate level increases, with decreasing blood flow. These metabolites tended to change more rapidly below a blood flow threshold, rather than showing a steady decrease as the blood flow was reduced, although the variability of the data precluded us from establishing this with confidence. Topographical study of tissue pH often showed sharp boundaries between zones of very low pH and regions with normal pH.

Cerebral blood flow in dementia.

Twenty-four patients of comparable age, blood pressure, and degree of dementia were classified by an "Ischemic Score" based on clinical features into "multi-infarct" and "primary degenerative" dementia. Regional cerebral blood flow (CBF) was measured by the intracarotid xenon 133 method. Both groups showed a decreased proportion of rapidly clearing brain tissue (largely gray matter). Cerebral blood flow per 100 gm brain per minute was normal in the primary degenerative group but low in the multi-infarct group. This suggests the blood flow is adequate for metabolic needs of the brain in patients with primary degenerative dementia but inadequate for those with multi-infarct dementia. There was no correlation between degree of dementia and CBF in the primary degenerative group but an inverse relationship existed in the multi-infarct group. Reactivity of blood vessels to reduction of arterial carbon dioxide pressure was normal in both groups.

Three cases of craniopharyngioma showing optic tract hypersignal on MRI.

Three patients presenting with visual failure had MRIs with hypersignal extending from the region of the optic chiasm along both optic tracts in 2 cases, and along 1 optic tract in the 3rd. In all patients intrinsic tumor of the chiasm was the most likely diagnosis based on MRI appearances, but all 3 had craniopharyngioma.

Cerebrovascular carbon dioxide reactivity and conductance in patients awake and under general anesthesia.

Paired cerebral blood flow measurements at two levels of arterial carbon dioxide (CO2) tension were made in 36 awake patients and 85 patients under general anesthesia to measure the percent change in flow per mm Hg change in PaCO2 (CO2 reactivity). CO2 reactivity was significantly greater in the generally anesthetized (5.96) than in the awake group (3.65). In both groups, a linear correlation was found between mean percent CO2 reactivity and conductance (the reciprocal of resistance), up to a level of conductance of 0.85 in awake and 0.95 in unconscious patients. When the CO2 reactivity of 18 awake patients and 59 unconscious patients was compared with that of respective control groups, only 11 patients were found to have abnormal CO2 reactivities for their conductance levels.

Involvement of dopaminergic receptors in quinolinate-induced striatal lesions.

The purpose of this study was to examine the effects of blockade (sulpiride) and activation (quinpirole) of dopaminergic D2 (DA2) receptors on brain lesions subsequent to excessive activation of glutamate (GLU) receptors. Striatal lesions were produced by direct injection of quinolinic acid, an endogenous GLU receptor agonist. Sulpiride (100 mg kg-1 i.p., 30 min before quinolinic acid injection and 1 h after) significantly (p < or = 0.05) reduced the volume of the lesion by around 20%. Quinpirole (1.25 mg kg-1 i.p., 30 min before quinolinic acid injection) had no effect. The protective action of DA2 receptor blockade strongly suggests that quinolinic acid-induced excitotoxicity may be partly modulated by DA2 receptors.

Combined intracerebral microdialysis and electrophysiological recording: methodology and applications.

A microdialysis probe is described that can simultaneously monitor indices of electrical activity, ionic homeostasis and changes in the composition of the extracellular fluid at the same brain site in anaesthetised laboratory animals. The probe is no larger than its conventional counterpart and avoids tissue injury problems due to implantation of separate recording electrodes. Examples are given of its application to the study of changes following probe implantation, cerebral ischaemia and local high K(+)-induced depolarisation.

Gliomatosis cerebri: report of a case presenting as a focal cerebral mass.

Gliomatosis cerebri (syn. astrocytomatosis cerebri) is a rare diffuse neoplastic condition affecting all parts of the brain. The clinical and pathological features of an unusually diffuse and histologically uniform case of gliomatosis cerebri are presented. Many tumour cells stained positively for glial fibrillary acid protein, confirming the astrocytic derivation of this neoplasm. Differing views on the nature of gliomatosis cerebri are briefly discussed.

Extracellular potassium activity, evoked potential and tissue blood flow. Relationships during progressive ischaemia in baboon cerebral cortex.

Extracellular K+ activity (Ke), local tissue blood flow and the cortical evoked potential (EP) were measured concurrently in the cerebral cortex of baboons anaesthetised with a-chloralose. Flows were progressively reduced from normal by occlusion of the middle cerebral artery and controlled steps of exsanguination. Our data suggest that 3 stages may be identified in the disturbance of K+ homeostasis produced by progressive ischaemia. In the first stage, at flow levels similar to those sufficient to abolish the EP (12-16 ml/100 g/min), small, self-limiting increases in Ke occur, probably reflecting K+ efflux into the extracellular space (ECS) with partial impairment of K+ clearance from the ECS. The second stage occurs at distinctly lower (P less than 0.01) levels of flow (8-11 ml/100 g/min), and is characterized by a massive (30-80 mM) increase in Ke, which we attribute to an increase in ionic permeability of cell membranes with further impairment or overloading of K+ clearance mechanisms. In the third stage, at flows below about 6-8 ml/100 g/min, the data indicate an inverse relationship between flow and Ke with persisting high Ke levels, suggesting complete loss of K+ clearance. Transient increases of Ke also occur in the flow range 4-13 ml/100 g/min, the rate of recovery of Ke in their decay phase being positively corelated with flow (P less than 0.005).

Reversibility of ischaemically induced changes in extracellular potassium in primate cortex.

Following the massive increase in extracellular potassium activity that occurs in cerebral cortex when local blood flow falls below 8--11 ml/100 g/min, recovery of potassium toward normal levels might be expected when flow is restored. This study assessed the reversibility of such potassium increases, produced by middle cerebral artery occlusion in 13 baboons anaesthetised with alpha-chloralose, in relation to a wide range of ischaemic duration and density and post-occlusion flow. Potassium was measured with ion-exchanger microelectrodes and flow by hydrogen clearance. The artery was occluded for 136 +/- 63 min (mean +/- SD) and measurements were continued thereafter for 93 +/- 57 min without systemic hypertension. Upon reperfusion, partial or complete recovery (i.e., to within control confidence limits) of potassium was seen in all animals, but the rate of recovery varied widely and potassium clearance showed bi-compartmental characteristics in 7 animals. The fast component (or initial slope) rate constant was significantly correlated with post-occlusion flow and (inversely) with the duration of occlusion for which flow fell below the arbitrary threshold of 10 ml/100 g/min (the flow deficit). The slow component was unrelated to these quantities. Complete recovery was associated with a significantly higher post-occlusion flow, and smaller flow deficit, than was partial recovery. Secondary increases in potassium, associated with relatively high flow deficits and post-occlusion flows, were seen in 5 animals. These results are discussed in terms of factors that may determine potassium clearance and the possibility that elevated levels of potassium (demonstrated here to be prolonged well into the post-occlusion phase) might influence the evolution of a cortical infarct.

Central conduction time as an index of ischaemia in subarachnoid haemorrhage.

Central conduction time (CCT) has been measured in 12 healthy volunteers, and in 16 patients admitted to a neurosurgical unit following subarachnoid haemorrhage. Twelve of the patients were subsequently operated upon for the obliteration of an intracranial aneurysm. CCT has been found to have low standard deviation in control cases, and in the normal side following subarachnoid haemorrhage from aneurysms in the Circle of Willis, and to be prolonged during the development of ischaemic complications, either of the haemorrhage or following surgery. Evidence so far suggests that CCT may be useful as a monitor of developing ischaemia in association with surgery for subarachnoid haemorrhage.

Changes in regional cortical tissue oxygen tension and cerebral blood flow during temporary middle cerebral artery occlusion in baboons.

Cortical tissue oxygen measured by a platinum cathode, and cerebral blood flow recorded by a hydrogen clearance technique, were measured in 13 baboons before, during and after temporary occlusion of the middle cerebral artery. Mean control pO2 was 23.8 +/- 14 mm Hg and mean flow 51.3 +/- 12 ml/100g/min. During the occlusion, there was a gradation in pO2 from values in the opercular area of 3.6 +/- 5.9 mm Hg, to values in the high parietal area of 11.9 +/- 11.7, these being statistically different (P less than 0.05) from each other. The corresponding flow values were 5.5 +/- 7.5 (opercular) and 22.3 +/- 21.7 ml/100 g/min parietal (P less than 0.01). Following removal of the MCA clip, between 20% and 30% of the electrodes registered an early hyperoxia and hyperaemia, which lasted up to 5 min. A late and prolonged hyperoxia, with less evidence of hyperaemia, was also noted in about 20%. The mean tissue pO2, however, at 5-min intervals up to 40 min following the removal of the clip only reached 60-80% of control values in the most ischaemic areas. Only the parietal region showed a mean pO2 above control levels. The mean flow data were uniformly reduced in all regions to about 80% of control values. During and after a second occlusion in 6 animals, similar changes were noted but with even fewer instances of hyperoxia. The mean oxygen and flow results were lower than with the first occlusion, but the reduction was not significant. There was no overall effect of hypercapnia on cortical tissue pO2 during the control period, but there was a significant (P less than 0.05) reduction during the same procedure after the period of ischaemia. An increase in pO2 during hypercapnia could be observed if there were arousal responses of blood pressure "spikes".

Measurements of oxygen tension in the cerebral cortex of baboons.

A polystyrene-covered platinum electrode (100-150 mum diameter) has been used to measure cortical tissue oxygen tension in baboon brains. The method of preparation, calibration, and the importance of small residual current (less than 40 nA) as an attribute of a reliable electrode, are described. With electrodes of this size, there was a large (16 +/- 12nA/torr) and linear current output with pO2 changes. The effect of avrious gases in addition to oxygen is described; halothane inhalation increases the apparent pO2 and hydrogen, used for blood flow estimations, reduces the recorded pO2. In 48 separate electrode placements in 13 baboons, the mean cortical qo2 was 23.8 +/- 12 mm Hg, with a range from 1-79 mm Hg; following occlusion of one middle cerebral artery, 37 electrodes recorded a pO2 of less then 5 mm Hg pO2 Oscillations were invariably noted in control conditions, independent of blood pressure; these waves disappeared during MCA occlusion and appeared to be augmented following release of the clip. Blood pressure "spikes" produce immediate and synchronous changes in all electrodes entirely different from the spontaneous waves. Such blood pressure changes may mask the true effect of hypercapnia on tissue pO2 and, if ignored, may lead to erroneous assumptions regarding local neural control of the circulation, the increased pO2 secondary to hypertension being regarded as evidence of regional vasodilation. A SUdden change in inspired pO2-the "air test"-was performed in control conditions and following the ischaemic insult, and the rate of change of cortical pO2 compared. The gradient was significantly greater (P less than 0.05) following ischaemia, suggesting a changed ratio in the tissue's flow to oxygen requirements and/or a persisting vasodilatation.