Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. 1994

A T Blei, and S Olafsson, and G Therrien, and R F Butterworth
Department of Medicine, Lakeside VA Medical Center, Chicago, IL 60611.

Brain edema, leading to intracranial hypertension and brain herniation, is a major cause of death in fulminant liver failure. Astrocyte swelling is a prominent neuropathological feature in experimental fulminant liver failure. It has been postulated that the osmotic effects of glutamine, generated in astrocytes from ammonia and glutamate in a reaction catalyzed by glutamine synthetase, could mediate brain swelling. Normal rats and rats that received a portacaval anastomosis were infused with ammonium acetate or a sodium acetate control; brain water in cerebral cortex was measured with the gravimetry method, intracranial pressure by means of a cisterna magna catheter and cortical amino acids using high-performance liquid chromatography. Although brain edema was detected in both groups receiving ammonia, it was of a greater magnitude in portacaval anastomosis rats (80.94% + 0.17% vs. 80.24% + 0.09%, p < 0.01), resulting in the development of intracranial hypertension. When portacaval anastomosis rats were infused with ammonium acetate and pretreated with 150 mg/kg methionine-sulfoximine, an inhibitor of glutamine synthetase activity, brain edema was ameliorated and intracranial pressure did not rise. A dose-dependent reduction in brain glutamine levels was seen with increasing doses of methionine-sulfoximine; however, brain edema did not decrease beyond the 150 mg/kg dose, suggesting that the increase in brain water was not solely a result of glutamine accumulation. We conclude that brain edema of a magnitude that results in intracranial hypertension is more likely to develop in rats after portacaval anastomosis receiving a continuous ammonia infusion. The osmotic effects of glutamine appear to mediate, but only in part, the increase in brain water seen in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007427 Intracranial Pressure Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. Intracerebral Pressure,Subarachnoid Pressure,Intracerebral Pressures,Intracranial Pressures,Pressure, Intracerebral,Pressure, Intracranial,Pressure, Subarachnoid,Pressures, Intracerebral,Pressures, Intracranial,Pressures, Subarachnoid,Subarachnoid Pressures
D008297 Male Males
D008717 Methionine Sulfoximine Sulfoximine, Methionine
D011167 Portacaval Shunt, Surgical Surgical portasystemic shunt between the portal vein and inferior vena cava. Eck Fistula,Portacaval Anastomosis,Portacaval Shunt,Shunt, Surgical Portacaval,Surgical Portacaval Shunt,Anastomoses, Portacaval,Anastomosis, Portacaval,Fistula, Eck,Portacaval Anastomoses,Portacaval Shunts,Portacaval Shunts, Surgical,Shunt, Portacaval,Shunts, Portacaval,Shunts, Surgical Portacaval,Surgical Portacaval Shunts
D011559 Pseudotumor Cerebri A condition marked by raised intracranial pressure and characterized clinically by HEADACHES; NAUSEA; PAPILLEDEMA, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile TINNITUS. OBESITY is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic PAPILLEDEMA may lead to optic nerve injury (see OPTIC NERVE DISEASES) and visual loss (see BLINDNESS). Benign Intracranial Hypertension,Idiopathic Intracranial Hypertension,Intracranial Hypertension, Benign,Intracranial Hypertension, Idiopathic,Hypertension, Benign Intracranial,Hypertension, Idiopathic Intracranial
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001834 Body Water Fluids composed mainly of water found within the body. Water, Body
D001929 Brain Edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6) Brain Swelling,Cerebral Edema,Cytotoxic Brain Edema,Intracranial Edema,Vasogenic Cerebral Edema,Cerebral Edema, Cytotoxic,Cerebral Edema, Vasogenic,Cytotoxic Cerebral Edema,Vasogenic Brain Edema,Brain Edema, Cytotoxic,Brain Edema, Vasogenic,Brain Swellings,Cerebral Edemas, Vasogenic,Edema, Brain,Edema, Cerebral,Edema, Cytotoxic Brain,Edema, Cytotoxic Cerebral,Edema, Intracranial,Edema, Vasogenic Brain,Edema, Vasogenic Cerebral,Swelling, Brain
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response

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