Increased vulnerability to focal cerebral ischemia in osteopontin-deficient mice.

Increased vulnerability to focal cerebral ischemia in osteopontin-deficient mice.

Field: Other

Authors: Cronberg, Tobias
Murozono, Michihiro
Franzén, Ahnders
Wieloch, Tadeusz

Address of presenting
author: Dr Tobias Cronberg
Avd. för Experimentell Hjärnforskning
Wallenberg Neurocentrum
Universitetssjukhuset
221 85 Lund

E-mail: Tobias.Cronberg@expbr.lu.se

Phone: 046-222 0605

Fax: 046-222 0615

Text of abstract: Increased vulnerability to focal cerebral ischemia in osteopontin-deficient mice.

Osteopontin ( Opn ) is a secreted glycoprotein, which production is upregulated after focal cerebral ischemia in the rat. Opn inhibits inducible nitric oxide synthase, iNOS, in rat vascular tissue. Disruption of the Opn-gene is associated with reduced tolerance to acute renal ischemia.

Aim: To study the effect of Opn depletion in a mouse model of transient focal cerebral ischemia.

Method: Opn knock-out mice and age-matched, wild-type controls were subjected to 30´ occlusion of the right middle cerebral artery using a filament inserted through the external carotid artery. To accomplish reperfusion the filament was withdrawn and the animals were allowed to recover. During and immediately after ischemia CBF was measured by laser doppler. The animals were sacrificed after 48 hours or 7 days respectively, by perfusion fixation with paraformaldehyde. The brains were sectioned and stained with NeuN ab. Infarct volume was estimated using a CCD-video camera and NIH-image software. In two separate groups of animals physiological parameters and serum-Ca²⁺ content was measured.

Results: After 48 hours of reperfusion the Opn-deficient mice have developed significantly larger infarcts than the mice in the wild-type group have. For the mice in the 7 day recovery group this increase is not statistically significant. The Opn deficient mice have a significantly higher mortality than wild-type littermates in the 7 day recovery group. There was no significant differencence between wild-type and knock-out mice concerning physiological parameters or serum-Ca²⁺ levels.

Conclusions: Osteopontin is of importance in the development of cerebral infarction after focal ischemia and seems to have a neuroprotective role. To study the long-term effect on infarct size a shorter ischemic period might be beneficial to reduce mortality. Reduced iNOS inhibition is one possible explanation for the increased vulnerability to ischemia in the osteopontin deficient animals.

Keywords: osteopontin,focal ischemia,NeuN,iNOS

	Increased vulnerability to focal cerebral ischemia in osteopontin-deficient mice.
Field:	Other
Authors:	Cronberg, Tobias Murozono, Michihiro Franzén, Ahnders Wieloch, Tadeusz
Address of presenting author:	Dr Tobias Cronberg Avd. för Experimentell Hjärnforskning Wallenberg Neurocentrum Universitetssjukhuset 221 85 Lund
E-mail:	Tobias.Cronberg@expbr.lu.se
Phone:	046-222 0605
Fax:	046-222 0615
Text of abstract:	Increased vulnerability to focal cerebral ischemia in osteopontin-deficient mice. Osteopontin ( Opn ) is a secreted glycoprotein, which production is upregulated after focal cerebral ischemia in the rat. Opn inhibits inducible nitric oxide synthase, iNOS, in rat vascular tissue. Disruption of the Opn-gene is associated with reduced tolerance to acute renal ischemia. Aim: To study the effect of Opn depletion in a mouse model of transient focal cerebral ischemia. Method: Opn knock-out mice and age-matched, wild-type controls were subjected to 30´ occlusion of the right middle cerebral artery using a filament inserted through the external carotid artery. To accomplish reperfusion the filament was withdrawn and the animals were allowed to recover. During and immediately after ischemia CBF was measured by laser doppler. The animals were sacrificed after 48 hours or 7 days respectively, by perfusion fixation with paraformaldehyde. The brains were sectioned and stained with NeuN ab. Infarct volume was estimated using a CCD-video camera and NIH-image software. In two separate groups of animals physiological parameters and serum-Ca²⁺ content was measured. Results: After 48 hours of reperfusion the Opn-deficient mice have developed significantly larger infarcts than the mice in the wild-type group have. For the mice in the 7 day recovery group this increase is not statistically significant. The Opn deficient mice have a significantly higher mortality than wild-type littermates in the 7 day recovery group. There was no significant differencence between wild-type and knock-out mice concerning physiological parameters or serum-Ca²⁺ levels. Conclusions: Osteopontin is of importance in the development of cerebral infarction after focal ischemia and seems to have a neuroprotective role. To study the long-term effect on infarct size a shorter ischemic period might be beneficial to reduce mortality. Reduced iNOS inhibition is one possible explanation for the increased vulnerability to ischemia in the osteopontin deficient animals.

Keywords:	osteopontin,focal ischemia,NeuN,iNOS

Index

Created 2000-03-15

Department of Physiological Sciences, Lund University

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