Erythrocyte-Bound Tissue Plasminogen Activator is Neuroprotective in Experimental Traumatic Brain Injury

被引：0

作者：

Stein, Sherman C. ^{[1
]}

Ganguly, Kumkum ^{[5
]}

Belfield, Caitlin M. ^{[1
]}

Xu, Xiangsheng ^{[1
]}

Swanson, Edward W. ^{[1
]}

Chen, Xiao-Han ^{[1
]}

Browne, Kevin D. ^{[1
]}

Johnson, Victoria E. ^{[1
]}

Smith, Douglas H. ^{[1
]}

LeBold, David G. ^{[1
]}

Cines, Douglas B. ^{[2
]}

Muzykhantov, Vladimir R. ^{[3
,4
]}

机构：

[1] Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19106 USA

[2] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19106 USA

[3] Univ Penn, Sch Med, Inst Environm Med, Inst Translat Med, Philadelphia, PA 19106 USA

[4] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19106 USA

[5] Los Alamos Natl Lab, Div B, Los Alamos, NM USA

来源：

JOURNAL OF NEUROTRAUMA | 2009年 / 26卷 / 09期

关键词：

blood-brain barrier; microclots; tissue plasminogen activator; traumatic brain injury; FIBRINOLYSIS; CLEARANCE; AFFINITY; DAMAGE; RAT;

D O I：

10.1089/neu.2008.0720

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

The purpose of this study was to test the effects of exogenous tissue plasminogen activator (tPA) in traumatic brain injury (TBI). We tested two different tPA formulations, free tPA and tPA bound to erythrocytes (RBC/tPA). Vehicle and each of the tPA treatments were injected intravenously into anesthetized rats 15 min after moderate lateral fluid percussion injury. The animals were sacrificed at 2 days for calculating microclot burden (n = 13) and IgG staining area (n = 13) in the brain sections as indicators of post-traumatic thrombosis and blood-brain barrier (BBB) breakdown, respectively. Another set of injured animals treated in the same way were sacrificed at 7 days to compare cortical lesion volumes (n = 28) and CA3 hippocampal cell loss (n = 24). All evaluations were done blinded with respect to treatment. No significant differences were found with respect to microclot burden or IgG staining volume. Injection of wild-type tPA caused significantly (p < 0.05) larger cortical injuries and greater cerebral hemorrhage. In contrast, there was significantly less cortical injury (p < 0.01) and hippocampal cell loss (p < 0.01) in the RBC/tPA group than in all other groups. These results reveal that RBC/tPA is more neuroprotective in experimental TBI than is unbound tPA.

引用

页码：1585 / 1592

页数：8