title: Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion.
abstract: The present experiments were undertaken to define changes in tissue calcium metabolism in focal and perifocal ("penumbral") tissues following 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extracellular calcium concentration ([Ca2+]e) was measured with ion-selective microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell from a normal value of about 1.2 mM to values around 0.1 mM, suggesting translocation of virtually all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however, [Ca2+]e never returned to normal but stabilized at about 50% of the control value for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e showed the expected transient decreases associated with spreading depression-like (or ischemic) depolarization waves. Recirculation was followed by return of [Ca2+]e towards normal values. In the focus, water content increased from about 79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of recirculation, the edema was aggravated (mean values 81.9% and 81.2%, respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and 83.8%, respectively). In the penumbra, no significant edema was observed until 6 h and 24 h of recirculation. The total tissue calcium content in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two- to threefold, compared with control. Changes in the penumbra were qualitatively similar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In focal areas, cells fail to extrude the calcium that is gradually accumulated during reperfusion and show massive calcium overload after the first 4-6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation.
authors.affiliation: Division of Experimental Brain Research, University Hospital, Lund, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Kristián
authors.forename: G
authors.initials: G
authors.lastname: Gidö
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
authors.forename: A
authors.initials: A
authors.lastname: Schütz
authors.forename: B K
authors.initials: BK
authors.lastname: Siesjö
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002544:Cerebral Infarction / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D002118:Calcium