Inflammatory and injury responses to ischemic stroke in obese mice.
OBJECTIVE
Although epidemiological studies reveal an increased incidence of obesity and an association between obesity and the prevalence/severity of ischemic stroke, little is known about the mechanisms that link obesity to ischemic stroke. This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion.


METHODS
The adhesion of leukocytes and platelets in cerebral venules, blood-brain barrier permeability, brain water content, and infarct volume were measured in wild-type, obese (ob/ob), and leptin-reconstituted ob/ob mice subjected to 30 minutes middle cerebral artery occlusion and reperfusion. Tissue and plasma cytokine levels were determined by cytometric bead array, and a role for monocyte chemoattractant protein-1 and interleukin-6 was assessed using blocking antibodies.


RESULTS
Compared with wild-type mice, ob/ob exhibited larger increases in leukocyte and platelet adhesion, blood-brain barrier permeability, water content, and infarct volume after middle cerebral artery occlusion-reperfusion. Reconstitution of leptin in ob/ob mice tended to further enhance all reperfusion-induced responses. Ob/ob mice also exhibited higher plasma levels of monocyte chemoattractant protein-1 and interleukin-6 than wild-type mice. Immunoneutralization of monocyte chemoattractant protein-1, but not interleukin-6, reduced infarct volume in ob/ob mice.


CONCLUSIONS
Obesity worsens the inflammatory and injury responses to middle cerebral artery occlusion and reperfusion by a mechanism independent of leptin deficiency. monocyte chemoattractant protein-1 appears to contribute to the exaggerated responses to ischemic stroke in obese mice.
Terao
Satoshi
S
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Yilmaz
Gokhan
G
Stokes
Karen Y
KY
Ishikawa
Mami
M
Kawase
Takeshi
T
Granger
D Neil
DN
D000818:Animals; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000150:complications* / Q000503:physiopathology; D002199:Capillary Permeability; D002448:Cell Adhesion; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D002560:Cerebrovascular Circulation; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism*; D004660:Encephalitis / Q000209:etiology* / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000494:pharmacology; D007962:Leukocytes; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D010973:Platelet Adhesiveness; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology; D020521:Stroke / Q000150:complications* / Q000209:etiology / Q000503:physiopathology
D018932:Chemokine CCL2; D015850:Interleukin-6; D020738:Leptin