Abstract
Traumatic brain injury (TBI) induces astrocytic and microglial activation and proliferation and augmented production of the cytokine interleukin-1β (IL-1β) and nerve growth factor (NGF). The increase in NGF temporally follows the increase in IL-1β, suggesting that the IL-1β up-regulation after trauma directly induces the increase in NGF. We examined the effect of IL-1 receptor antagonist protein (IL-1ra) on microglial proliferation and NGF production in rat cortex, following two different models of TBI. Rabbit fibroblasts infected with a retroviral vector containing the human IL-1ra gene were implanted into the wound cavity immediately following a cortical stab wound or 6 hours after a weight drop-induced trauma. Both microglial proliferation and NGF up-regulation were decreased significantly in animals receiving IL-1ra-expressing cells compared with animals receiving naive (untransfected) fibroblasts. These data demonstrate that the increase in NGF after central nervous system trauma is directly mediated through IL-1β and that blocking IL-1β following brain injury leads to suppression of an NGF- mediated reparative response. Such blockade of inflammation, however, may prove to be of significant therapeutic benefit in human brain injury and other inflammatory states.
Original language | English (US) |
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Pages (from-to) | 123-127 |
Number of pages | 5 |
Journal | Annals of neurology |
Volume | 39 |
Issue number | 1 |
DOIs | |
State | Published - 1996 |
ASJC Scopus subject areas
- Neurology
- Clinical Neurology