Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion

M. L. Ruehl, J. A. Orozco, M. B. Stoker, P. F. McDonagh, Bruce M Coull, Leslie S Ritter

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Early intervention after acute ischemic stroke is essential to minimize brain cell injury. Although reperfusion of the ischemic brain is the treatment of choice for acute stroke, reperfusion itself may cause additional injury. The inflammatory cascade, characterized in part by early leukocyte interaction with endothelium, may contribute to this additional injury to blood vessels and surrounding brain tissue, extending the area of infarction. The selectin family of adhesion molecules mediates the initial, rolling and tethering of leukocytes to endothelium. P-selectin is rapidly expressed on ischemic endothelium in the brain vasculature, and L-selectin is expressed on leukocytes. Blocking the selectin-mediated tethering step may limit the inflammatory component of reperfusion injury in the brain. Fucoidin (FCN), a competitive inhibitor of P- and L-selectin, has been reported to decrease leukocyte accumulation during reperfusion of other organs. The effect of both leukocyte and endothelial selectin inhibition after cerebral ischemia and reperfusion has not been previously examined. The purpose of this study was to determine the effects of selectin adhesion molecule blockade on cerebral infarction size and neurological function after middle cerebral artery occlusion and reperfusion (MCAO-R) in the rat. MCAO was induced using the filament method. All animals were subjected to 4 h of MCAO and 24 h of reperfusion. After 24 h, brains were analyzed for size of infarction. Neurological function was assessed during stroke and 24 h after reperfusion. Two groups were studied, an untreated control group (n = 9) and a group treated with the selectin inhibitor, fucoidin (25 mg kg-1) (n = 9). We found that selectin blockade significantly reduced cerebral infarction size by 50% (p < 0.05) and improved neurological function (p < 0.05). In addition, a trend toward decreased cerebral edema was demonstrated with selectin inhibition. These results indicate that treatment of the blood and the endothelium with a selectin anti-inflammatory agent is protective after focal stroke and reperfusion in the rat.

Original languageEnglish (US)
Pages (from-to)226-232
Number of pages7
JournalNeurological Research
Volume24
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Selectins
Reperfusion
Blood Vessels
Stroke
Endothelium
Leukocytes
Brain
L-Selectin
P-Selectin
Cerebral Infarction
Infarction
Leukocyte Rolling
Middle Cerebral Artery Infarction
Brain Edema
Wounds and Injuries
Reperfusion Injury
Brain Ischemia
Brain Injuries
Anti-Inflammatory Agents
Control Groups

Keywords

  • Inflammation
  • Ischemia/reperfusion
  • Leukocytes
  • Middle cerebral artery occlusion
  • Selectins
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion. / Ruehl, M. L.; Orozco, J. A.; Stoker, M. B.; McDonagh, P. F.; Coull, Bruce M; Ritter, Leslie S.

In: Neurological Research, Vol. 24, No. 3, 2002, p. 226-232.

Research output: Contribution to journalArticle

Ruehl, M. L. ; Orozco, J. A. ; Stoker, M. B. ; McDonagh, P. F. ; Coull, Bruce M ; Ritter, Leslie S. / Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion. In: Neurological Research. 2002 ; Vol. 24, No. 3. pp. 226-232.
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