Abstract：
:Following a traumatic brain injury (TBI), the excessive release of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) is a major cause of cerebral edema, which, in turn, can cause permanent neuronal loss and cognitive deficits in laboratory rats. This study examined the changes in expression of the proinflammatory cytokines IL-1beta and TNF-alpha after progesterone (8 mg/kg) or allopregnanolone (4 mg/kg) treatment in brain-injured rats at 3, 8, and 12 h and 6 days post-injury. Adult male rats received either bilateral prefrontal cortical contusion or sham surgery. The hormones were given intraperitoneally at 1 and 6 h, and continued once per day for up to 5 days. The gene expression of IL-1beta and TNF-alpha was measured by mRNA using real-time quantitative reverse transcripted polymerase chain reaction (RT-PCR). The protein concentrations of IL-1beta and TNF-alpha were measured using enzyme-linked immunosorbent assay (ELISA) to confirm the translation from mRNA to protein. The results indicated that progesterone and allopregnanolone reduce both IL-1beta and TNF-alpha at 3 h post-injury, when the expression of these cytokines peaks. At 8 and 12 h post-injury, IL-1beta and TNF-alpha gene expression in injured rats was still elevated compared to shams. By the sixth day post-injury, cytokine expression was back to the level of intact rats. We conclude that progesterone and allopregnanolone may attenuate the production of proinflammatory cytokines early after TBI, and this may be one mechanism by which progesterone and allopregnanolone reduce cerebral edema and promote functional recovery from TBI.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
He J,Evans CO,Hoffman SW,Oyesiku NM,Stein DGdoi
10.1016/j.expneurol.2004.06.008keywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
404-12issue
2eissn
0014-4886issn
1090-2430pii
S0014488604002390journal_volume
189pub_type
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