Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 28, Issue 11, Pages 1786-1794Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2008.73
Keywords
allopregnanolone; coagulation; hemostasis; progesterone; traumatic brain injury
Categories
Funding
- NINDS [1RO1N540825, 1RO1N538664]
- Department of Emergency Medicine at Emory University
Ask authors/readers for more resources
Our laboratory has shown in numerous experiments that the neurosteroids progesterone (PROG) and allopregnanolone ( ALLO) improve molecular and functional outcomes after traumatic brain injury (TBI). As coagulopathy is an important contributor to the secondary destruction of nervous tissue, we hypothesized that PROG and ALLO administration may also have a beneficial effect on coagulation protein expression after TBI. Adult male Sprague-Dawley rats were given bilateral contusions of the medial frontal cortex followed by treatments with PROG ( 16 mg/kg), ALLO ( 8 mg/kg), or vehicle (22.5% hydroxypropyl-beta-cyclodextrin). Controls received no injury or injections. Progesterone generally maintained procoagulant (thrombin, fibrinogen, and coagulation factor XIII), whereas ALLO increased anticoagulant protein expression (tissue-type plasminogen activator, tPA). In addition, PROG significantly increased the ratio of tPA bound to neuroserpin, a serine protease inhibitor that can reduce the activity of tPA. Our findings suggest that in a model of TBI, where blood loss may exacerbate injury, it may be preferable to treat patients with PROG, whereas it might be more appropriate to use ALLO as a treatment for thrombotic stroke, where a reduction in coagulation would be more beneficial.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available