Development of posttraumatic hyperthermia after traumatic brain injury in rats is associated with increased periventricular inflammation

Posttraumatic hyperthermia (PTH) is a noninfectious elevation in body temperature that negatively influences outcome after traumatic brain injury (TBI). We sought to (1) characterize a clinically relevant model and (2) investigate potential cellular mechanisms of PTH. In study 1, body temperature patterns were analyzed for 1 week in male rats after severe lateral fluid percussion (FP) brain injury (n = 75) or sham injury (n = 17). After injury, 27% of surviving animals experienced PTH, while 69% experienced acute hypothermia with a slow return to baseline. A profound blunting or loss of circadian rhythmicity (CR) that persisted up to 5 days after injury was experienced by 75% of brain-injured animals. At 2 and 7 days after injury, patterns of cell loss and inflammation were assessed in selected brain thermoregulatory and circadian centers. Significant cell loss was not observed, but PTH was associated with inflammatory changes in the hypothalamic paraventricular nucleus (PVN) by one week after injury. In brain-injured animals with altered CR, reactive astrocytes were bilaterally localized in the suprachiasmatic nucleus (SCN) and the PVN. Occasional IL-1beta+/ED-1 + macrophages/microglia were observed in the PVN and SCN exclusively in brain-injured animals developing PTH. In animals with PTH there was a significant positive correlation (r = 0.788, P < 0.01) between the degree of postinjury hyperthermia and the total number of cells positive for inflammatory markers within selected thermoregulatory and circadian nuclei. In study 11, a separate group of animals underwent the same injury and temperature monitoring paradigm as in study 1, but had additional physiologic data obtained, including vital signs, arterial blood gases, white blood cell counts, and C-reactive protein levels. All parameters remained within normal ranges after injury. These data suggest that PTH and the alteration in CR of temperature may be due, in part, to acute reactive astrocytosis and inflammation in hypothalamic centers responsible for both thermoregulation and CR.