Examination of the metabolism of oedematous brain tissue

Summary We induced oedema in rabbit brains by applying cold to a defined area of the intact dura for a constant time. 24 hours later the animals were killed, and a piece of brain cortex adjacent to the region of cold application and an exactly similar piece from the other hemisphere were removed. In both pieces we determined the water content, the water uptake of the sliced brain in vitro, and the glucose metabolism of the brain slices. Respiration, carbon dioxide production in the presence of bicarbonate, consumption of glucose, and production of lactate and pyruvate were measured. The incubations were made in physiological saline with different concentrations of glucose (2.5 ml, 5 mM, and 10 mM).The mean difference of the water contents in vivo was 1.9%. The water uptake in vitro did not depend on the glucose concentration.The oedematous tissue had a slightly stimulated respiration, and its aerobic glycolysis was markedly increased.The respiration was independent of the glucose concentration. The lactate: pyruvate quotient was somewhat higher on the oedematous side, and it became greater on both sides with increasing glucose concentration.The glycolysis increased considerably between 2.5 mM and 5 mM glucose, especially in the oedematous brain. Between 5 mM and 10 mM glucose the aerobic glycolysis was accelerated only slightly by increasing glucose concentration.We think that the increased glycolysis is an expression of a preceding energy deficit. By a simple enhancement of the glucose concentration to more than 100 mg/100 ml the metabolism is not stimulated further, and the water content is not diminished.Supported by the Deutsche Forschungsgemeinschaft: H. 573/3.Part of the Dissertation, Med. Fakultät Homburg (Saar), 1972.     

Light and electron microscope study of nerve cells in traumatic oedematous human cerebral cortex

The cerebral cortex of eight patients with complicated head and brain traumatic injuries has been examined with light and transmission electron microscopes. The neuronal and neuroglial cell bodies and their processes have been examined to study the changes induced by the brain injury and the associated vasogenic and cytotoxic, moderate or severe, brain oedema. Light microscopy study showed oedematous and ischaemic neurons and neuroglial cells in both moderate and severe oedema, and breakdown of the blood-brain barrier with perivascular and parenchymatous haemorrhagic foci. Astrocytes and oligodendrocytes exhibited oedematous and reactive changes. At the electron micro scope level oedematous changes were found in intraneuronal and glial somatic compartment. Myelinated axons showed clear and dark degenerative features. Beaded dendrites and clear and dense synaptic degeneration were also found. The extracellular space appeared distended, with the presence of clear and electron dense haematogenous oedema fluid and fibrinous organization. Phagocytosis of degenerated myelinated axons and synaptic endings by neuroglial cells and non nervous invading cells were observed. The clinical evolution time of traumatic brain injuries was considered in relation to nerve cell degenerative features.     

Examination of the metabolism of oedematous brain tissue

Summary Oedema were induced in rabbit brains by the application of cold metal to defined areas of intact dura for constant times. Trephine openings were made over the right cerebral hemispheres. 24 hours later the animals were killed, and identical pieces of occipital cortex from both hemispheres were removed. In all specimens we determined the water content, the water uptake of the sliced brain in vitro, and the glucose metabolism of the brain slices. Respiration, carbon dioxide production in the presence of bicarbonate, consumption of glucose, and production of lactate and pyruvate were measured. The incubations were made in physiological saline (with K⁺, Ca²⁺, Mg²⁺ and PO₄ ³- additions) in the presence of gas mixtures with different contents of oxygen.The mean difference of the water contents in vivo was 1.3%. The lowest water content after in vitro incubations was found in the presence of 95% O₂ and 5% CO₂.The oedematous tissue had a slightly stimulated respiration, and its aerobic glycolysis was markedly increased. These metabolic differences were observed only in the presence of 12% O₂ and 5% CO₂ and higher oxygen concentrations. In the presence of 4% O₂ and 5% CO₂ neither respiratory nor glycolytic differences existed between normal and oedematous tissue.A pronounced Pasteur effect was seen in all the experiments. Increase in glycolysis is a more sensitive indicator of oxygen lack than is decrease in respiration.During 150 min of incubation respiration and carbon dioxide production become slower. The decrease in total and glycolytic CO₂ production is greater in slices of control hemispheres than in slices of oedematous hemispheres.The best correlation between metabolic activities determined by manometry and metabolic activities determined by glucose, lactate and pyruvate determinations was found in experiments in the presence of 4% O₂ and 5% CO₂. It is concluded that unsliced brain in the presence of air, at room temperature and below, has nearly the same respiration and glycolysis within the whole glucose degradation process as have brain slices at 38 °C in the presence of 4% O₂ and 5% CO₂.The conclusion is made that in vitro the best metabolic situation for brain slices, normal and oedematous, is between 20% and 95% of oxygen.Supported by the Deutsche Forschungsgemeinschaft: He 573/3.With technical assistance from E. Seifert and H. Verfürth.     

Experimental transplantation gliomas in the adult cat brain

Experimental brain tumours were produced in adult cats by stereotactic xenotransplantation of the rat glioma clone F98. Regional ATP, glucose and lactate were measured after 2-4 weeks on coronal cryostat sections by substrate-induced bioluminescence, potassium content was imaged by the histochemical sodium cobaltinitrite method, and regional pH by incubating cryostat sections with the fluorescent pH-indicator umbelliferone. The regional biochemical alterations were correlated with magnetic resonance imaging and tissue water content. Biochemical changes were heterogeneous in tumours but exhibited a rather uniform pattern in peritumoural oedema. ATP was consistently reduced, glucose and lactate were increased and pH was more alkaline than in normal white matter. The decrease of ATP matched the increase of water, indicating that ATP decline represents fractional dilution in the oedematous tissue rather than break-down of energy metabolism. The increased lactate levels, therefore, may originate from the tumour and not from a metabolic disturbance in the peritumoural oedematous tissue. The implications of this interpretation for the pathogenesis of peritumoural oedema are discussed.     

Rapid clinical deterioration in a patient with multi-focal glioma despite corticosteroid therapy: a quantitative MRI study

A patient with high-grade multi-focal glioma deteriorated rapidly despite high dose corticosteroid therapy (dexamethasone: 16 mg/day). MRI was used to measure diffusion tensor parameters and longitudinal relaxation time (T1) values of peritumoural oedematous brain before and after commencing steroid treatment. Forty-eight hours after steroid treatment there was no evidence of brain oedema reduction. Specifically, regions of oedematous brain showed a significant increase in mean diffusivity () with a significant decrease in diffusion anisotropy (p < 0.05), but without any change in T1 values. These quantitative MRI data were mirrored by the rapid deterioration seen when assessing the patient clinically. This case shows that quantitative MRI can not only measure steroid treatment response but also failure in patients with malignant gliomas.     

Extracellular space and electrolyte distribution in cortex and white matter of dog brain in cold induced oedema

Summary 24 hours after a circumscribed cold injury of the cortex dog brains were perfused from the lateral ventricle and the frontal subarachnoidal space to the cisterna magna with an artificial CSF containing trace amounts of³⁵S-labelled thiosulphate. Simultaneously the extracellular tracer was administered intravenously. Extracellular fluid volume was estimated and found to be increased from 10 to 15% in the oedematous cortex and from 10 to 27% in the oedematous white matter. The actual size of ECS in oedematous white matter, however, must be larger as indicated by the relative alterations of thiosulphate distribution, tissue water, sodium and chloride. Apparently a small part of the fluid accumulation affects the cellular compartment in oedematous white matter. It may be concluded from the close spatial correspondence of the spreading of I¹³¹ albumin and Evans blue, the increase in water and sodium content, and the enlargement of the TSS that the dilated extracellular channels are filled with a plasma like oedema fluid, derived from blood.This investigation was supported by a grant from the Deutsche Forschungsgemeinschaft.     

Examination of the metabolism of oedematous brain tissue

Glucose and gas metabolism as well as water, sodium, and potassium content of normal and oedematous white matter slices of rabbit brain have been determined. A cutting technique for the preparation of the slices is described. Although the increase of the relative water content in oedematous white matter is much more pronounced than in oedema of the grey matter, we observed only one significant change: the pyruvate production in vitro is about 20% higher in slices prepared from oedematous brain.     

Edematous cerebellar infarction. A clinico-pathological study of 16 cases

Sixteen cases of cerebellar infarction with brain stem compression and tonsillar herniation were studied post-mortem. None was operated. Cardiac embolism was the most common cause (75% of the cases). Infarction involved the superior cerebellar artery territory in 8 cases, and multiple cerebellar artery territories (including in each case the posterior inferior cerebellar artery territory) in 8 cases. It involved the cerebellum only in 10 cases. In the 6 other cases, it was associated with an infarct in the paramedian territory of the brain stem. The oedematous swelling was linked to the large size, the rostral site and the embolic causes of the infarct. Cases with massive infarction of the brain stem differed from others by severe motor weakness of the limbs in 5 cases and a deep coma in the 6th. On the contrary, only one of the 10 cases with lone cerebellar infarct had a mild hemiparesis. Thus, when a hemi- or tetraplegia occurred in the course of an oedematous cerebellar infarction, an associated massive paramedian infarction of the pons must be suspected rather than a brain stem compression. This can be taken into account when a surgical treatment is discussed.     

Novel entry point for intraoperative ventricular puncture during the transsylvian approach

Summary Objective. In dealing with cases of oedematous brain, relaxation during the transsylvian approach to supratentorial aneurysms has been accomplished by ventricular drainage by using the anatomic point defined by Dr. Paine. However, we have experienced patient complications when using this point. We propose a novel anatomic point to reduce catheter-related complications and facilitate adequate ventricular puncture during ruptured aneurysm operations. Methods. Ten patients underwent aneurysmal neck clipping for ruptured aneurysm by means of the transsylvian approach. The use of a novel anatomic point for intraoperative drainage was examined using a neuronavigation system. Results. Using the novel point of entry for ventricular cannulation proved to be reliable for puncture and reduced chance of malpositioning. Conclusion. Secure intraoperative ventricular cannulation is reliably achieved by pointing the catheter approximately 2 cm beyond a line extending from the anterior limb of the triangle described by Paine. This technique reduces injury to the deep brain and enhances preciseness and safety of ventricular cannulation.     

Improved brain protection at decompressive craniectomy--a new method using Palacos R-40 (methylmethacrylate)

A new method is described for protecting the brain after decompressive craniectomy in which a temporary methylmethacrylate flap is formed, somewhat larger than the original bone flap, thus gaining "extra" volume for the oedematous brain in which to expand. The present procedure was developed as a part of ordinary clinical practice particularly in response to demands from the NICU staff and our colleagues at other clinics who were responsible for the care of the patient in the post NICU period. They made us keenly aware that these patients frequently lack optimal co-ordination and balance and therefore run an increased risk of trauma to the unprotected brain when falling. This prompted us to develop a method for brain protection after decompressive craniectomy aiding in the care and rehabilitation until the final installation of the patient's own bone flap can be performed.     

Multiple tuberculomas of the brain

A case of multiple tuberculomas of the brain in a pregnant patient is reported. The symptoms and signs suggested a lesion of the cerebellum which was found to be only congested and oedematous at craniotomy. The correct diagnosis was made at autopsy.     

Measurement of changes in brain water in man by magnetic resonance imaging

John Hunter was undoubtedly aware of the water content of normal brain tissue, and described cerebral oedema. The advent of nuclear magnetic resonance (NMR) shed new light on brain water, and the derivation of spatial information and hence images from NMR signals, has permitted studies of regional brain water in man in vivo. The initial study described here tested whether NMR longitudinal relaxation time (T1) correlates with brain water content in the cerebral cortex and white matter in man, and significant relationships have been demonstrated in cortex (r = 0.65, P less than 0.002) and white matter (r = 0.94, P less than 0.0001), the latter having narrow 95% confidence limits. The residual variance allows the prediction of water content from the T1 of white matter, measured from the image of a single patient, with an accuracy of +/- 4% of total tissue water with 95% confidence. In the further study described, the effects of dexamethasone and an infusion of 20% mannitol on brain water content has been assessed in patients with intrinsic cerebral tumours. Dexamethasone had no significant effect on the T1 of normal brain, oedematous peritumoural white matter, or tumour tissue. It must be concluded that the water content of these tissues is not changed by dexamethasone and that the clinical improvement seen in patients with cerebral tumours immediately after dexamethasone has to be explained by some mechanism other than a reduction in cerebral oedema. Mannitol did reduce the T1 of oedematous peritumoural white matter, and the T1 of tumour tissue, but did not change the T1 of normal brain significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

The impact of intestinal ischaemia-reperfusion on caerulein-induced oedematous experimental pancreatitis

BACKGROUND: Intestinal ischaemia is a feature of severe acute pancreatitis. It is not known whether intestinal ischaemia and reperfusion contributes to the progression from mild to severe pancreatitis. AIM: The aim of this study was to examine the impact of intestinal ischaemia-reperfusion on caerulein-induced oedematous experimental pancreatitis. METHOD: Male Wistar rats (n = 48) were randomised to 6 experimental groups: controls (CO), saline infusion (S), saline infusion and intestinal ischaemia-reperfusion (SIR), caerulein infusion (C), caerulein and sham operation (CS), and caerulein infusion with intestinal ischaemia reperfusion (CIR). Caerulein was infused over 6 h to induce mild oedematous pancreatitis. Clamping the superior mesenteric artery for 10 min induced mild intestinal ischaemia. The reperfusion time was 24 h. The primary end point was histology of the pancreas at 24 h. RESULTS: There was no significant difference in histologic severity of pancreatitis at 24 h (Kruskal-Wallis, p = 0.37). CONCLUSION: The severity of acute oedematous pancreatitis was not increased by 10 min of intestinal ischaemia followed by 24 h of reperfusion.     

Extent of thermal penetration of Nd-YAG laser — histological considerations

Summary The extent of thermal penetration of Nd-YAG laser was studied histologically. The material was obtained from seven cases of various types of intracranial and extracranial tumours and normal temporal muscle obtained at operation. After irradiation of the tumour surface with the laser, the tumours were removed and depth and width of pathological changes caused by heat were studied. Histologically, materials consisted of a vaporized surface, carbonized, vesicular, necrotic, oedematous layers and surrounding intact brain tumour tissue. There was a direct relationship between the thermal effect and the irradiated thermal energy (watt × exposure time × pulse number). The results showed that the thermal effect was limited to a depth of 6 to 10 mm from the irradiated surface when irradiated 4 times at the power of 90 watts for 2 seconds.     

Peritumoral oedema and lipid content

Summary The authors analyzed the water and lipid contents of oedematous tissues of white matter obtained during the operation, comparing with the absorption value in the CT scan. As the absorption value lowered its level, the water content increased, while the lipid decreased. However, after subtracting these two components, the content of protein also showed a significant decrement parallel to the absorption value despite the existence of extravasated protein. The decrement of lipid content was considered to be due to a dilution effect by an expanded volume of extravasated oedema fluid, as well as the decrease in protein, rather than the actual loss of tissue component; that is demyelination. It is the relative decrease in protein content which contributes to the low absorption value of oedematous tissue.     

Morphological astrocytic changes in complicated human brain trauma. A light and electron microscopic study

The astrocytic changes and reactivity in human brain trauma complicated with subdural haematoma or hygroma have been analysed in nine patients. Cortical biopsies of frontal, temporal and parietal regions were examined with light and transmission electron microscopy. At light microscopy level oedematous clear and dense astrocytes, binucleated and multinucleated atrocytes and hypertrophic reactive astrocytes were distinguished in either moderate or severe vasogenic brain oedema. Swollen, clear and dense perineuronal astrocytes were observed compressing and indenting dark, degenerated pyramidal and non pyramidal nerve cells. At electron microscopy level glycogen depleted and glycogen rich astrocytes were found in some patients. Dense and reactive hypertrophic astrocytes exhibited increased amounts of dilated smooth endoplasmic reticulum, microtubules, lipofucsin granules, gliofilaments and alpha type glycogen particles. In severe oedema the astrocytic ensheathment of synaptic contacts is lost, the perivascular astrocyte end feet appeared dissociated from the capillary basement membrane and the interastrocytary gap junctions are disrupted. The posttraumatic neurological deficits and the neurobehavioural disorders of the patient studied are correlated with astrocyte ultrastructural changes and blood brain barrier disruption.     

Interstitial white matter brain oedema does not alter the electroencephalogram.

An experimental study was performed to determine the effects of interstitial white mater oedema on the electroencephalogram (EEG). Using both rodent and feline infusion models of focal brain oedema no difference was found between the EEG waveforms recorded epidurally from the infused and control hemispheres. It is concluded that where focal slow-wave EEG abnormalities overlie oedematous brain the EEG abnormalities are not primarily related to the brain oedema but arise from either local biomechanical or other pathophysiological mechanisms.     

Transfalcine approach to a contralateral hemispheric tumour

Summary In this report an interhemispheric transfalcine approach for contralateral hemispheric tumours is described. This surgical approach was successfully employed for 4 tumours situated in the parafalcine region. The approach provided direct access to the tumour avoiding the need to retract oedematous brain on the tumour affected side. The possible indications and advantages of such an operation are discussed.     

Improved brain protection at decompressive craniectomy – a new method using Palacos<Superscript>⌖</Superscript> R-40 (methylmethacrylate)

Summary A new method is described for protecting the brain after decompressive craniectomy in which a temporary methylmethacrylate flap is formed, somewhat larger than the original bone flap, thus gaining extra volume for the oedematous brain in which to expand.The present procedure was developed as a part of ordinary clinical practice particularly in response to demands from the NICU staff and our colleagues at other clinics who were responsible for the care of the patient in the post NICU period. They made us keenly aware that these patients frequently lack optimal co-ordination and balance and therefore run an increased risk of trauma to the unprotected brain when falling. This prompted us to develop a method for brain protection after decompressive craniectomy aiding in the care and rehabilitation until the final installation of the patients own bone flap can be performed.     

Endotoxin and antiendotoxin antibodies in patients with acute pancreatitis.

OBJECTIVE: To elucidate the time course of endotoxaemia and antiendotoxin antibodies in patients with acute pancreatitis. DESIGN: Prospective clinical study. SETTING: University hospital, Germany. SUBJECTS: 25 patients with oedematous (n = 9) or necrotising (n = 16) pancreatitis, and 20 healthy controls. MAIN OUTCOME MEASURES: Concentrations of endotoxin and immunoglobulins (classes G, M, and A) directed at two lipid A molecules, four lipopolysaccharides, and alpha-haemolysin of Staphylococcus aureus measurements in plasma during a 12 day period. RESULTS: There were no differences in the degree of endotoxaemia between patients with oedematous and necrotising pancreatitis on admission. However, from the day after admission and throughout the observation period patients with necrotising pancreatitis had significantly higher concentrations of endotoxin than those with oedematous pancreatitis. Concentrations of IgM specific for endotoxin peaked at day 4, and then decreased in patients with oedematous pancreatitis while remaining high for those with necrotising pancreatitis. There was only a slight increase in IgA specific for endotoxin, and IgG and immunoglobulins to gamma-haemolysin remained steady throughout the observation period. There was strong cross-reactivity (r > 0.7) between IgM specific for endotoxin (70%), but this was less with IgA (52%), and IgG (20%). CONCLUSIONS: Necrotising pancreatitis is accompanied by persistent endotoxaemia with an extended rise in antiendotoxin antibodies. Patients with oedematous pancreatitis have a transient endotoxaemia with a temporary increase of Ig specific for endotoxin. Endotoxin stimulates the synthesis of specific antibodies (IgM) despite general immunosuppression.