Mild hypothermia reduces secondary damage after traumatic brain injury(TBI) in rats, even when applied after injury. Recent studies suggest that the beneficial effects of hypothermia after TBI, however, are not mediated by reduced excitotoxcicity or energy demands. Mechanisms of benefit remain to be determined. We reported that TBI induces an acute inflammatory response(adhesion molecule upregulation and neutrophil [PMN] accumulation) in rat brain. Since PMN accumulation may be associated with blood-brain barrier injury and hyperemia, we hypothesized that hypothermia would reduce acute inflammation after TBI.

Methods: Sprague-Dawley rats were anesthetized and subjected to TBI by controlled cortical impact to the left parietal cortex. Brain temperature was controlled at 32°C, 37°C, or 39°C (n = 8/group) for 4 h after TBI, then rats were immediately decapitated. Immunohistochemistries were performed on brain sections using MoAbs that recognize PMN (RP-3), ICAM-1 (TM-8, Athena Neurosciences), or polyclonal Ab that reacts with E-selectin (LaRoche), and quantitated in 65-75 (100x) fields. PMN accumulation was also quantified with myeloperoxidase assay (MPO). Absolute neutrophil count (ANC) was measured in blood samples before, 1 h, and 4 h after TBI. Results: PMN accumulation in injured brain was decreased in rats maintained at 32°C vs 39°C (4 fold by MoAb, p < 0.05; 8 fold by MPO, p = 0.08). E-selectin was induced after TBI (p < 0.05), and only modestly decreased at 32°C vs. 39°C (p = 0.11). ICAM-1 was not up-regulated at this early time after TBI. ANC was not affected by temperature. Conclusions: Compared to hyperthermia, hypothermia reduces early PMN accumulation after TBI, without a significant decrease in adhesion molecule expression or systemic ANC. Hypothermia may confer some of its anti-inflammatory effects following TBI by qualitative changes that occur on neutrophils during inflammation, such as avidity changes in adhesion molecules. Support: 2P50 NS30318-04A21 from NINDS.