Gray Matter Edema Research Articles

Abstract TP400: Intravenous Glibenclamide Reduces Water Uptake and Mass Effect in Large Hemispheric Infarction (GAMES-RP Study)

Introduction: Prior studies have shown a linear relationship between CT-derived density and brain water uptake. We sought to determine whether intravenous (IV) glibenclamide (glyburide; BIIB093) would reduce water uptake and mass effect on serial CT scans from patients enrolled in the phase 2 GAMES-RP trial. Methods: Non-contrast CT scans performed between admission and day 7 (n=263) were analyzed in patients in the GAMES-RP modified intention-to-treat sample. Midline shift (MLS) was measured at the level of maximal lateral displacement of the septum pellucidum. CT-derived radiodensity was measured in pre-defined regions of interest (ROI) within the infarct. The same ROIs were mirrored to the contralateral hemisphere. The change in CT radiodensity (change in water uptake) was averaged among gray and white matter regions separately, and across both regions together. Repeated measures mixed effects models were used to assess the effect of IV glibenclamide on MLS or CT-measured water uptake. Results: There was a median of 3 CT scans [IQR 2-5] per patient during the first 7 days after stroke. Greater change in water uptake was associated with more MLS (β=0.17, 95% CI 0.15 to 0.20, p <0.0001). Using repeated measures models, treatment with IV glibenclamide was associated with reduced water uptake (β= -2.25, 95% CI -4.37 to -0.13, p =0.037) and reduced MLS (β= -1.78, 95% CI -2.87 to -0.67, p =0.002), and adjusted for time. Treatment with IV glibenclamide reduced both gray and white matter water uptake independently. In mediation analysis, gray matter edema (β=0.10, 95% CI 0.05 to 0.16, p <0.001) mediated a greater proportion of MLS when compared to white matter (β=0.02, 95% CI -0.03 to 0.08, p =0.427). Conclusions: IV glibenclamide reduced water uptake and MLS after large hemispheric infarction. A phase 3 study is underway to determine whether IV glibenclamide treatment improves clinical outcome.

Posterior Reversible Encephalopathy Syndrome in Pregnancy: Experience in Two Cases

ABSTRACT Posterior reversible encephalopathy syndrome (PRES) is a clinical-neuroradiological entity characterized by headache, vomiting, confusion, seizures and blurred vision along with images suggesting white gray matter edema in posterior regions of the brain as shown by magnetic resonance imaging (MRI).1 The term PRES describes a potentially reversible imaging appearance and may occur in diverse situations, including hypertension, eclampsia, pre-eclampsia, immunosuppressive medications, such as cyclosporine, various antineoplastic agents, severe hypercalcemia, thrombocytopenic syndromes, Henoch-Schönlein purpura, hemolytic uremic syndrome, amyloid angiopathy, systemic lupus erythematosus (SLE), renal failure, post-transplantation, infection and sepsis4 (Gram-positive organisms predominate). We report two cases of acute PRES who had eclampsia and presented with recurrent episodes of seizures and hypertension. The authors emphasize that even though PRES is usually reversible, the early recognition and management of this syndrome is important to prevent permanent neurological sequelae. Treatment of PRES needs to be early and aggressive with rapid control of convulsions and arterial hypertension. Although prognosis is favorable, delay in treatment can sometimes lead to cerebral ischemia and infarct. How to cite this article Mehta P, Rani GU, Syamala O. Posterior Reversible Encephalopathy Syndrome in Pregnancy: Experience in Two Cases. J South Asian Feder Obst Gynae 2016;8(1):79-81.

Assessment of the neuroprotective effects of the acetylcholinesterase inhibitor huperzine A in an experimental spinal cord trauma model.

Spinal cord injury is nowadays still a challenging disease, and a treatment option aimed at the primary site of injury does not currently exist. Therefore, the management of acute spinal cord injury has recently focused on the reasons behind the aggravation of the initial insult through secondary mechanisms, and the search for pharmacological treatment protocols is generally aimed at reducing and minimizing the neural injury and neurological sequela. The secondary spinal cord injury usually develops following a primary lesion induced by spinal cord contusion and the emergence of apoptotic cells has been found to play an important role in the development of secondary injury. We propose that huperzine A may induce a significant reduction in the number of apoptotic cells because it possesses the ability to protect cells against glutamate, ischemia and staurosporine-induced cytotocity and apoptosis. Huperzine A was administered intraperitoneally to male Wistar Albino rats (220-340 g of body weight) after moderate static clip compression (70 g for 60 s) of the spinal cord at T7 level. Neurological functions were assessed using the Basso-Beattle-Breshanan (BBB) motor rating scale until 3th and 7th days before perfusion, following which the spinal cord was harvested for histopathological examinations and apoptotic cell counts. Histopathological evaluations of the spinal cord of the control, trauma and huperzine A treated groups were evaluated. Control group showed normal neuronal and vascular structures of the spinal cord. However, in both trauma groups 3rd- and 7th-day perfusion showed extensive cavitation and hemorrhage, areas of necrosis and edema in gray matter, and degeneration in motor neurons along with patchy areas of necrotic and apoptotic cells. In the group treated with huperzine A, an increased number of normal cells was observed, along with a lower number of necrotic cells, with a significant reduction in the apoptotic cells (P<0.01). The administration of huperzine A improved post-trauma motor performance. Furthermore, BBB scores of all groups showed that there was an improvement of locomotor abilities in the treatment group as compared with the control. When compared with controls, huperzine A treatment demonstrates a significant reduction in the number of apoptotic cells. In addition, the group treated with huperzine A showed significant and appreciable neurological improvement in rats.

Multimodal imaging approach to cerebral gas embolism lesions

Cerebral gas embolism may be revealed by the sudden onset of unconsciousness sometimes after surgery or after diagnostic and therapeutic procedures. The clinical diagnosis may be difficult if the context is not relevant. Imaging can therefore play a crucial role in revealing the presence of intracranial gas bubbles on CT or MRI scans. This report is of a case of fatal cerebral gas embolism revealed by CT and MRI performed for deep and unexplained coma. Etiological diagnosis revealed the presence of a lung tumor invading the mediastinum, thus possibly allowing the migration of gas from the lung to the arterial cerebral circulation. A second MRI performed 8 days after the initial event with diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) allowed better comprehension of the pathophysiological mechanisms of cerebral injury secondary to gas embolism by showing two kinds of cerebral lesions: white-matter vasogenic edema and cytotoxic gray-matter edema.

Reoxygenation stress on blood–brain barrier paracellular permeability and edema in the rat

The blood–brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1 h) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 h time course in conjunction with paracellular permeability, gray matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of 14C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6–18 h time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min–1 h reoxygenation time points; and the second increase at only the 24 h time point. Analysis of serum derived cytokines (IL-1β, TNFα, IL-6, IL-10, and IFNγ) demonstrated that only IL-1β and IL-6 were at detectable levels, but these levels were similar to controls. White blood cell counts showed significant decreases in lymphocytes (10 min–3 h), increases in monocytes (10 min–3 h and 12 h), and increases in polymorphonuclear cells (1 h and 3 h). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.

A Newborn Who Has Seizures

At 4 days of age, an infant was admitted to the county hospital with an elevated temperature and poor feeding. He was treated for 3 days for presumed sepsis. Two days after discharge, he develops tachypnea and jittery movements and is admitted to the university hospital. Upon arrival, he is having a tonic-clonic seizure that lasts for 5 minutes, followed by a hypotonic phase.The baby is transferred to the neonatal intensive care unit where physical examination reveals hyperirritability, a bulging fontanel, tachypnea, and mild dehydration. Lumbar puncture reveals 400 cells/mm3, and cefotaxime plus amikacin are administered empirically for meningitis.Computed tomography (CT) scan demonstrates ventricular dilatation and gaping of cranial sutures (Fig. 1).An extraventricular catheter is placed for drainage. During the course of therapy, Escherichia coli is isolated from the cerebrospinal fluid and blood cultures. The infant has continuous seizure activity despite anticonvulsant therapy. The head circumference increases significantly secondary to obstructive hydrocephalus.Ultrasonography of the head performed 1 week later reveals bilateral white and gray matter edema without signs of superior sagittal sinus thrombosis. High signal intensity is apparent in the basal ganglia, with dilatation of both ventricles in which septa are detected, presumably due to meningitis. Left middle cerebral artery blood flow is decreased. Magnetic resonance imaging (MRI) performed 1 day later reveals localized areas of infarct in the bilateral thalamic nuclei and left cerebral parietal and frontal lobe gyri. Edema makes it impossible to differentiate white and gray matter. An area of subdural hematoma is evident in the right parietal region (Fig. 2).The patient’s status deteriorates dramatically in the next few days, with disseminated intravascular coagulation and respiratory distress that requires initiation of mechanical ventilation. CT performed 10 days after hospital admission demonstrates diffuse hypodensity within all cerebral and cerebellar hemispheres as well as a centrally hypodense region that has irregular hyperdense borders within the right basal ganglia. Dural surfaces, gyri within the left vertex, and the right basal ganglia are enhanced with contrast material (Fig. 3).One month after the initiation of the therapy, the patient’s neurologic status has not changed. Pupils are not reactive to light, and the infant has hypotonia with absent tendon reflexes. A second MRI shows hyperintensity of all cortical gyri, which is interpreted as subacute hemorrhage (Fig. 4). Regions within the left parietal cortex also show subdural hematoma. The patient dies 2 days later after sudden cardiopulmonary arrest.Stroke associated with heterozygosity for factor V Leiden and meningitis.The true incidence of perinatal stroke is not known, but has been reported as ranging from approximately 1 in 4,000 live births to as high as 17% in autopsy studies of term newborns. The etiologic factors responsible for neonatal cerebral infarction are diverse, as are the clinical presentation and the long-term neurodevelopmental outcomes. Infarction may be due to either thrombotic or embolic causes, and major roles may be played by placental thrombi, congenital heart diseases, sepsis, traumatic vascular damage, consumptive coagulopathy, or metabolic disorders. Blood disorders associated with stroke in neonates include polycythemia, protein-C deficiency, prothrombin 20210A mutation, and the fVL mutation. Multiple factors are associated with a high risk of thrombosis. The fVL mutation, a dominantly inherited coagulation abnormality, has been found in association with cerebral arterial and venous disorders in neonates and children. The fVL mutation is the most common inherited cause of thrombosis in Caucasians. Alone, the fVL mutation does not greatly increase risk, but its presence can interact with other genetic and environmental factors to increase risk. Infants who have stroke associated with the fVL mutation typically develop symptoms within the first postnatal months, but only if additional endogenous or exogenous risk factors for thrombosis are present.Heterozygosity for FV R506Q confers an estimated 5- to 10-fold increased risk of venous thrombosis; homozygosity may be associated with a 50- to 100-fold increased risk. Perinatal stroke has been reported as a complication of meningitis, disseminated intravascular coagulation, and sepsis. Infection leads to a hypercoagulable state. During serious infection, there is a rapid destruction of protein C and antithrombin III, both of which normally inhibit coagulation. Infection also produces endothelial injury and a release of inflammatory cytokines, which lead to the downregulation of thrombomodulin and upregulation of tissue factor. The catastrophic deterioration of the patient in this case was related to the diffuse brain infarction developing within 1 week. Although meningitis can induce stroke by itself, rapid progression of diffuse infarcts is augmented by the fVL mutation.JoDee M. Anderson, MD, Division of Neonatal Medicine, Oregon Health & Science University, Portland, Ore.

Fast tissue segmentation based on a 4D feature map in characterization of intracranial lesions

The aim of this work was to develop a fast and accurate method for tissue segmentation in magnetic resonance imaging (MRI) based on a four-dimensional (4D) feature map and compare it with that derived from a 3D feature map. High-resolution MRI was performed in 5 normal individuals, in 12 patients with brain multiple sclerosis (MS), and 9 patients with malignant brain tumors. Three inputs (proton-density, T2-weighted fast spin-echo, and T1-weighted spin-echo MR images) were routinely utilized. As a fourth input, either magnetization transfer MRT was used or T1-weighted post-contrast MRI (in patients only). A modified k-nearest neighbor segmentation algorithm was optimized for maximum computation speed and high-quality segmentation. In that regard, we a) discarded the redundant seed points; b) discarded the points within 0.5 standard deviation from the cluster center that were non-overlapping with other tissue; and c) removed outlying seed points outside 5 times the standard deviation from the cluster center of each tissue class. After segmentation, a stack of color-coded segmented images was created. Our new technique utilizing all four MRI inputs provided better segmentation than that based on three inputs (P < 0.001 for MS and P < 0.001 for tumors). The tissues were smoother due to the reduction of statistical noise, and the delineation of the tissues became sharper. Details that were previously blurred or invisible now became apparent. In normal persons a detailed depiction of deep gray matter nuclei was obtained. In malignant tumors, up to five abnormal tissue types were identified: 1) solid tumor core, 2) cyst, 3) edema in white matter 4) edema in gray matter, and 5) necrosis. Delineation of MS plaque in different stages of demyelination became much sharper. In conclusion, the proposed methodology warrants further development and clinical evaluation. J. Magn. Reson. Imaging 1999;9:768–776. © 1999 Wiley-Liss, Inc.

Fast tissue segmentation based on a 4D feature map in characterization of intracranial lesions.

The aim of this work was to develop a fast and accurate method for tissue segmentation in magnetic resonance imaging (MRI) based on a four-dimensional (4D) feature map and compare it with that derived from a 3D feature map. High-resolution MRI was performed in 5 normal individuals, in 12 patients with brain multiple sclerosis (MS), and 9 patients with malignant brain tumors. Three inputs (proton-density, T2-weighted fast spin-echo, and T1-weighted spin-echo MR images) were routinely utilized. As a fourth input, either magnetization transfer MRT was used or T1-weighted post-contrast MRI (in patients only). A modified k-nearest neighbor segmentation algorithm was optimized for maximum computation speed and high-quality segmentation. In that regard, we a) discarded the redundant seed points; b) discarded the points within 0.5 standard deviation from the cluster center that were non-overlapping with other tissue; and c) removed outlying seed points outside 5 times the standard deviation from the cluster center of each tissue class. After segmentation, a stack of color-coded segmented images was created. Our new technique utilizing all four MRI inputs provided better segmentation than that based on three inputs (P < 0.001 for MS and P < 0.001 for tumors). The tissues were smoother due to the reduction of statistical noise, and the delineation of the tissues became sharper. Details that were previously blurred or invisible now became apparent. In normal persons a detailed depiction of deep gray matter nuclei was obtained. In malignant tumors, up to five abnormal tissue types were identified: 1) solid tumor core, 2) cyst, 3) edema in white matter 4) edema in gray matter, and 5) necrosis. Delineation of MS plaque in different stages of demyelination became much sharper. In conclusion, the proposed methodology warrants further development and clinical evaluation.

Role of Blood Clot Formation on Early Edema Development After Experimental Intracerebral Hemorrhage

Blood "toxicity" is hypothesized to induce edema and brain tissue injury following intracerebral hemorrhage (ICH). Lobar ICH in pigs produces rapidly developing, marked perihematomal edema (>10% increase in water content) associated with clot-derived plasma protein accumulation. Coagulation cascade activation and, specifically, thrombin itself contribute to edema development during the first 24 hours after gray matter ICH in rats. In the present study, we sought to determine whether blood clot formation is necessary for edema development by comparing intracerebral infusions of heparinized and unheparinized blood in pig (white matter) and in rat (gray matter). We also examined heparin's effect on thrombin-induced gray matter edema. In pigs, we infused autologous blood (with or without heparin) into the cerebral white matter to produce lobar hematomas and froze the brains in situ at 1, 4, or 24 hours after ICH. We determined hematomal and perihematomal edema volumes on coronal sections by computer-assisted morphometry. In rats, we infused either blood or thrombin (with or without heparin) into the basal ganglia and measured water, sodium, and potassium contents at 24 hours after ICH. In pigs, unheparinized blood induced rapid (at 1 hour) and prolonged (24 hours) perihematomal edema (average volume, 1.29+/-0. 20 mL; n=6). No perihematomal edema was present following heparinized blood infusions (n=6). In rats, unheparinized blood produced significantly greater edema than heparinized blood infusions. As with whole blood, thrombin-induced gray matter edema at 24 hours was significantly reduced by coinjection of heparin. After ICH, blood clot formation is required for rapid and prolonged edema development in perihematomal white and gray matter. Thrombin also contributes to prolonged edema in gray matter.

Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine

The possibility that serotonin can modify the early pathological sequences occurring in spinal cord trauma was investigated in a rat model. To that end we took advantage of the possibility of influencing serotonin pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before the production of the injury and compared the results with injured, untreated controls. A unilateral incision was made into the dorsal horn of the lower thoracic cord (about 2.5 mm deep, 4.5 mm long) and the rats were allowed to survive up to 5 h after the trauma. The injured region from untreated animals showed macroscopically at that time a pronounced swelling and the water content had increased by 3.5% as compared to intact controls. The segments rostral and caudal to the lesion also exhibited a profound increase in water content. Light microscopy revealed a significant expansion of the spinal cord as compared to controls. The swelling was most pronounced in the gray matter on the injured side. Electron microscopy showed distorted neurons, swollen astrocytes and extracellular edema in the gray matter in and around the primary lesion. There was also a sponginess in the surrounding white matter with disruption of myelin, collapsed axons and widened periaxonal spaces. Pretreatment of the rats with p-CPA significantly reduced the swelling of the injured spinal cord and there was no visible expansion. The ipsilateral edema in the central gray matter was considerable less pronounced as compared to that in untreated animals. The increase in water content was less than 1% in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Moderate hypothermia reduces postischemic edema development and leukotriene production.

Using the bilateral carotid artery occlusion model of cerebral ischemia in the gerbil, we studied the effect of moderate hypothermia (30 to 31 degrees C) on the postischemic production of prostanoids (cyclooxygenase pathway) and leukotrienes (lipoxygenase pathway) and accompanying changes in cerebral edema formation. Hypothermia capable of slowing central evoked potential conduction time was studied over the course of 40 minutes of cerebral ischemia and for up to 2 hours of reperfusion. The successful induction of cerebral ischemia was confirmed by somatosensory evoked potential amplitude changes. Measurements of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and leukotriene B4 (LTB4) (radioimmunoassay) and cerebral edema (specific gravity) were made at early (10 minutes) and late (2 hours) reperfusion times. Although both white and gray matter showed no early significant difference in edema accumulation between normothermic and hypothermic gerbils at 10 minutes of reperfusion, hypothermic animals demonstrated significantly less white matter edema (specific gravity, 1.0397 +/- 0.0010 vs. 1.0341 +/- 0.0012, P less than 0.01) and gray matter edema (specific gravity, 1.0408 +/- 0.0009 vs. 1.0365 +/- 0.0008, P less than 0.01) by 2 hours of reperfusion. Production of PGF1 alpha was not significantly different between normothermic and hypothermic animals during the reperfusion period; however, hypothermic gerbils demonstrated significantly lower production of LTB4 at 10 minutes reperfusion time compared to normothermic animals (1.49 +/- 0.79 vs. 5.28 +/- 1.49 pg/mg of protein, P less than 0.05). This difference between the two groups in LTB4 levels was no longer detectable at 2 hours of reperfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

The early phase of cryogenic lesions: an experimental model of seizures updated.

Following cryogenic lesions in 64 rabbits, epileptic activity and gray matter edema were correlatively investigated during the initial phase (23 h). Indexes were developed to allow a quantitative assessment of epileptic activity. The indexes demonstrated that the early phase of cryogenic epilepsy is a very rapid phenomenon during the first 4 h postlesion. Epileptic activity precedes brain edema, and in individual animals, there is a significant positive correlation between the total amount of epileptic activity and the total amount of edema. The relationship between epileptic activity and brain edema are most likely interrelated at the level of pathophysiological mechanisms and several mechanisms can be postulated.

Chronological sequences and blood-brain barrier permeability changes in local injury as assessed by nuclear magnetic resonance (NMR) images from sliced rat brain

Two experiments were done with a prototype mini-NMR imager to evaluate the potential application of nuclear magnetic resonance (NMR) imaging in neuropathology. Cryo-injury-induced brain edema in brain slices from 22 adult male rats was imaged for observing the chronological sequences. Blood-brain barrier permeability changes were evaluated in 12 other brain slice images. EDTA-2Na-Mn solution was intravenously injected as an indicator of blood-brain barrier permeability. Contrast was achieved by changing the NMR imaging parameters. High resolution imaging permitted visualization of the corpus callosum, the thickness of which was only 0.2-0.4 mm. The extent of edema in gray matter was clearly shown with a striking contrast; no consistent findings were seen with slight differences in water content between edema and the surrounding normal cortex. As a result, the chronological sequences of brain edema were clearly observed. Mn-EDTA leaking from the circulating blood through the damaged capillary wall had a paradoxical enhancement effect on the NMR images; this effect might be suitable for evaluating blood-brain barrier permeability changes in NMR images.

4394385 Treatment of gray matter edema

4394385 Treatment of gray matter edema

Chronological sequences and blood-brain barrier permeability changes in local injury as assessed by nuclear magnetic resonance (NMR) images from sliced rat brain.

Two experiments were done with a prototype mini-NMR imager to evaluate the potential application of nuclear magnetic resonance (NMR) imaging in neuropathology. Cryo-injury-induced brain edema in brain slices from 22 adult male rats was imaged for observing the chronological sequences. Blood-brain barrier permeability changes were evaluated in 12 other brain slice images. EDTA-2Na-Mn solution was intravenously injected as an indicator of blood-brain barrier permeability. Contrast enhancement was achieved by changing the NMR imaging parameters. High resolution imaging permitted visualization of the corpus callosum, the thickness of which was only 0.2-0.4 mm. The extent of edema in gray matter was clearly shown with a striking contrast; no consistent findings were seen with slight differences in water content between edema and the surrounding normal cortex. As a result, the chronological sequences of brain edema were clearly observed. Mn-EDTA leaking from the circulating blood through the damaged capillary wall had a "paradoxical enhancement" effect on the NMR images; this effect might be suitable for evaluating blood-brain barrier permeability changes in NMR images.

The amount of circumscribed brain edema and the degree of post-ischemic neuronal recovery do not correlate well.

Fifty-four dogs were exposed to multi-focal ischemia sufficient to maintain suppression of the P1--N1 amplitude of the cortical sensory-evoked response (CSER) for 60 minutes. Subsequently, the P1--N1 amplitude recovery of the CSER was followed for an additional 15, 60, or 120 min while the dogs were treated or left untreated. The combination of PGI2, indomethacin, and heparin promoted a statistically significant augmentation of CSER amplitude return relative to: 1) no treatment; 2) PGI2 alone; 3) indomethacin alone; 4) PGI2 and heparin; 5) indomethacin and heparin; 6) PGI2 and indomethacin. Percentage gray matter water by the wet weight/dry weight technique was significantly elevated in all embolized groups compared to ten non-embolized controls, but the percentage recovery of the CSER did not correlate with the presence or degree of gray matter edema among embolized animals followed for 1 hour. Separation of embolized animals by the presence or absence of "neuron-disabling" flows (defined as 0-15 ml/100 gm/min for gray matter and 0-6 ml/100 gm/min for white matter) did produce significantly different mean CSER percentage recoveries but percentage gray matter water in the two groups was comparable. A proposed explanation of the data is that brain ischemia engenders two parallel processes which may become uncoupled. Ischemia creates metabolic conditions that lead to increased cellular imbibition of water and produces increased vascular leakiness. These perturbations increase brain water content. Concomitantly, there is an occurrence of further metabolic derangements and multifactorial interaction at the blood-endothelial interface which have a direct influence on neuronal function and recovery.

Alterations in the distribution of water, sodium, potassium, and chloride in brain during the evolution of ischemic cerebral edema.

Abstract Experimental regional cerebral ischemia in the territory of the middle cerebral artery (MCA) in a primate (Macaca mulatta) was produced by selective embolization of the internal carotid artery bifurcation. Determinations of tissue dry weight (percentage) and tissue sodium, potassium, and chloride on samples from the affected and contralateral hemispheres were carried out periodically until 48 hours after the onset of focal cerebral ischemia. Samples from the cortex supplied by the occluded MCA showed excesses in water content, increases in sodium, and decreases in potassium as early as 3 to 4 hours after occlusion. Hemispheric swelling became apparent after 4 to 5 hours, with obvious “gray matter edema.” However, only minimal to moderate increases in the water content of the subcortical white matter (without change in electrolytes) were observed in the same brain sections. Subcortical white matter samples from the affected MCA territory showed gradual increases in water content at 12, 24, and 48 hours, but definite increases in sodium and decreases in potassium were not observed until 24 to 48 hours of ischemia. During this late phase, the “gray matter edema” remained unchanged or underwent partial resolution. Our results agree with data derived from morphological studies suggesting that ischemic cerebral edema develops in a diphasic fashion, with a primary phase of early “gray matter edema” evolving to a secondary phase of late “white matter edema.”

Alterations in the distribution of water, sodium, potassium, and chloride in brain during the evolution of ischemic cerebral edema

Experimental regional cerebral ischemia in the territory of the middle cerebral artery (MCA) in a primate (Macaca mulatta) was produced by selective embolization of the internal carotid artery bifurcation. Determinations of tissue dry weight (percentage) and tissue sodium, potassium, and chloride on samples from the affected and contralateral hemispheres were carried out periodically until 48 hours after the onset of focal cerebral ischemia. Samples from the cortex supplied by the occluded MCA showed excesses in water content, increases in sodium, and decreases in potassium as early as 3 to 4 hours after occlusion. Hemispheric swelling became apparent after 4 to 5 hours, with obvious “gray matter edema.” However, only minimal to moderate increases in the water content of the subcortical white matter (without change in electrolytes) were observed in the same brain sections. Subcortical white matter samples from the affected MCA territory showed gradual increases in water content at 12, 24, and 48 hours, but definite increases in sodium and decreases in potassium were not observed until 24 to 48 hours of ischemia. During this late phase, the “gray matter edema” remained unchanged or underwent partial resolution. Our results agree with data derived from morphological studies suggesting that ischemic cerebral edema develops in a diphasic fashion, with a primary phase of early “gray matter edema” evolving to a secondary phase of late “white matter edema.”

Experimental regional cerebral ischemia in the middle cerebral artery territory in primates. Part 2: Effects on brain water and electrolytes in the early phase of MCA stroke.

Acute regional cerebral ischemia was produced in the middle cerebral artery (MCA) territory in monkeys (Macaca mulatta) by selective embolization of the internal carotid (ICA) bifurcation with minimum surgical intervention in the neck under sedated conditions. Two of five hours after embolization, brain water (measurement of dry weight) and tissue concentration of sodium and potassium were determined in the tissues of the sylvian cortex, putamen and subcortical white matter in the affected MCA territory. As early as three hours, initial increase in brain water was detected in the samples of the putament without noticeable change in tissue electrolytes in two of three animals. Gross ischemic swelling of the gray matter, in both the sylvian cortex and putamen, became obvious in six of eight animals after four to five hours. This swollen gray matter showed marked increase in brain water (up to 36% swelling), increase in tissue sodium (up to 100% of the control value), and decrease in tissue potassium (down to 55%). On the other hand, edema in the white matter, if present at all, was minimal without detectable change in tissue electrolytes and was always accompanied by much greater ( greater than two to seven times) edema in the gray matter. Thus, the gray matter edema, in both the deep subcortical structures and the cortex, appeared to play the major role in the development of hemispheric swelling of the brain which may begin within hours of the onset of the MCA stroke in monkeys. Microscopically, the swollen gray matter which showed more than 10% swelling with a definite shift of tissue sodium and potassium content appeared to be dead tissue. However, early edema in the gray matter which showed less than 10% swelling without detectable change in electrolytes might be caused by simple diffusion of water through the dysfunctional capillary wall or cell membrane with or without a permeability gradient between the intravascular cerebrospinal fluid and cerebral tissue compartment and might possibly be reversible.