Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury
Wen-Hai Chou, … , Donna M. Ferriero, Robert O. Messing
Wen-Hai Chou, … , Donna M. Ferriero, Robert O. Messing
Published July 1, 2004
Citation Information: J Clin Invest. 2004;114(1):49-56. https://doi.org/10.1172/JCI21655.
View: Text | PDF
Article Neuroscience

Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

Abstract

Thrombolysis is widely used to intervene in acute ischemic stroke, but reestablishment of circulation may paradoxically initiate a reperfusion injury. Here we describe studies with mice lacking protein kinase Cδ (PKCδ) showing that absence of this enzyme markedly reduces reperfusion injury following transient ischemia. This was associated with reduced infiltration of peripheral blood neutrophils into infarcted tissue and with impaired neutrophil adhesion, migration, respiratory burst, and degranulation in vitro. Total body irradiation followed by transplantation with bone marrow from PKCδ-null mice donors reduced infarct size and improved neurological outcome in WT mice, whereas marrow transplantation from WT donors increased infarction and worsened neurological scores in PKCδ-null mice. These results indicate an important role for neutrophil PKCδ in reperfusion injury and strongly suggest that PKCδ inhibitors could prove useful in the treatment of stroke.

Authors

Wen-Hai Chou, Doo-Sup Choi, Hong Zhang, Dezhi Mu, Tom McMahon, Viktor N. Kharazia, Clifford A. Lowell, Donna M. Ferriero, Robert O. Messing

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Infarct size is reduced in PKCδ-null mice after transient, but not perma...
Infarct size is reduced in PKCδ-null mice after transient, but not permanent, MCAO. (A) Shown are representative images of TTC-stained brain slices after 20 hours of permanent MCAO from PKCδ+/+ and PKCδ –/ – mice. Viable tissue is stained red, whereas the ischemic area remains unstained (white). (B) Infarct size measured as a percentage of the area of the nonischemic hemisphere after 20 hours of permanent MCAO from PKCδ+/+ (n = 8) and PKCδ –/ – mice (n = 8). (C) Neurological deficit scores after 20 hours of permanent MCAO from PKCδ+/+ (n = 8) and PKCδ –/ – mice (n = 8). (D) Representative images of TTC-stained brain slices after 1 hour of MCAO and 24 hours of reperfusion from PKCδ+/+ and PKCδ –/ – mice. (E) Total infarct size after 1 hour of MCAO and 24 hours of reperfusion from PKCδ+/+ (n = 10) and PKCδ –/ – (n = 9) mice. (F) Neurological deficit scores after 1 hour of MCAO and 24 hours of reperfusion from PKCδ+/+ (n = 8) and PKCδ –/ – mice (n = 8). (G and H) Infarct size in the cerebral cortex (G) and striatum (H) after 1 hour of MCAO and 24 hours of reperfusion from PKCδ+/+ (n = 10) and PKCδ –/ – (n = 9) mice. *P < 0.05 compared with WT littermates (two-tailed, unpaired t test). P < 0.05 compared with WT littermates (one-tailed, unpaired t test).