title: Elevation of extracellular glutamate in the final, ischemic stage of progressive epidural mass lesion in cats.
abstract: Epidural mass lesions may cause ischemia due to progressive intracranial hypertension. In order to investigate the impact of intracranial pressure on accumulation of neuroactive substances, we gradually raised intracranial pressure in five halothane anesthetized cats by inflation of an epidural balloon. We evaluated in the parietal cortex contralateral to the site of balloon inflation, alterations of extracellular glutamate and purine catabolites and of the lactate/pyruvate ratio in relation to changes of intracranial, cerebral perfusion and mean arterial blood pressure. In a complementary experiment, regional cerebral blood flow was assessed by sequential positron emission tomography. In this simplified mass lesion model, extracellular glutamate increased in all cats at a late, critical stage after tentorial herniation, when intracranial pressure had increased to more than 90 mm Hg, cerebral perfusion pressure had decreased below 40-50 mm Hg. Positron emission tomography assessments revealed that the ischemic threshold for glutamate accumulation was in the range of 15-20 mL/100 g/min. Purine catabolites and the lactate/pyruvate ratio increased somewhat earlier than glutamate, but also after reaching the critical, terminal stage. We conclude that in this model of progressive epidural compression, glutamate-mediated excitotoxic processes at sites remote from the initial focal lesion depend on processes such as delayed ischemia in combination with tentorial herniation and systemic hypotension. These processes seem to be initiated by a decrease of cerebral perfusion pressure below a threshold of 40-50 mm Hg.
authors.affiliation: MPI für neurologische Forschung, Köln, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Toyota
authors.forename: R
authors.initials: R
authors.lastname: Graf
authors.forename: C
authors.initials: C
authors.lastname: Dohmen
authors.forename: M
authors.initials: M
authors.lastname: Valentino
authors.forename: M
authors.initials: M
authors.lastname: Grond
authors.forename: K
authors.initials: K
authors.lastname: Wienhard
authors.forename: W D
authors.initials: WD
authors.lastname: Heiss
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism*; D002415:Cats; D004824:Epidural Space / Q000378:metabolism* / Q000502:physiology; D005110:Extracellular Space / Q000000981:diagnostic imaging / Q000378:metabolism*; D018698:Glutamic Acid / Q000096:biosynthesis*; D019586:Intracranial Hypertension / Q000000981:diagnostic imaging / Q000378:metabolism*; D010296:Parietal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D011859:Radiography; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data
chemical_list: D018698:Glutamic Acid