Development of Posttraumatic Hyperthermia after Traumatic Brain Injury in Rats is Associated with Increased Periventricular Inflammation

Abstract

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 I, body temperature patterns were analyzed for 1 week in male rats after severe lateral fluid percussion (FP) brain injury (n ¼ 75) or sham injury (n ¼ 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-1b þ / ED-1 þ 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 ¼ 0.788, Po0.01) between the degree of postinjury hyperthermia and the total number of cells positive for inflammatory markers within selected thermoregulatory and circadian nuclei. In study II, a separate group of animals underwent the same injury and temperature monitoring paradigm as in study I, 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.

Longitudinal changes in the DTI measures, anti-GFAP expression and levels of serum inflammatory cytokines following mild traumatic brain injury

“…Available literature on experimental models of TBI indicate injury induction via fluid percussion or controlled cortical impact, where skull is invariably removed and direct trauma to the brain tissue, produces moderate to severe TBI (Morales et al, 2005) resulting in focal lesions, blood-brain barrier (BBB) disturbances, edema formation, and morphologically evident brain damage (Carbonell and Grady, 1999;Graham et al, 2000;Thompson et al, 2005). Since craniotomy is indispensable in these models, mTBI models developed through these methods may lead to ignoring some pathophysiological alterations speculated in mTBI.…”

Zaburzenia termoregulacji pochodzenia ośrodkowego — jak diagnozować i leczyć

“…24 post-trauma hours. In another experimental study by Thomson et al [10], brain damage resulted in CF in 27% of animals while acute hypothermia was observed in 69% of subjects. The development of CF was associated with the inflammatory changes within the hypothalamus.…”

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

“…In humans and laboratory animals, TBI can induce the accumulation of alpha-synuclein (Knoblach and Faden, 1998;Thompson et al, 2005a;Uryu et al, 2003), and a neuroinflammatory response (Csuka et al, 1999;Holmin and Hojeberg, 2004;Holmin et al, 1995), similar to what is observed in PD (Braak et al, 2002(Braak et al, ,2006Gerhard et al, 2006;Imamura et al, 2003;McGeer et al, 1988). Lateral fluid percussion (LFP) injury, a model of experimental TBI (McIntosh et al, 1989;Thompson et al, 2005a), induces the presence of silver-stained and lipofuschin-containing neurons in the substantia nigra (SN) of adult rats (Hicks et al, 1996). However, the phenotype of the injured neurons was not determined, and no stereological evaluation of the number of nigrostriatal neurons was performed (Hicks et al, 1996).…”