Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats

Abstract

The proinflammatory cytokine interleukin-1β (IL-1β) is induced rapidly after traumatic brain injury (TBI) and contributes to the inflammatory events that lead to neuronal loss. Although an important source of IL-1β is from the injured brain itself, in patients with multiple organ trauma (polytrauma) IL-1β is also released into the bloodstream which may potentially influence brain vulnerability. The purpose of this study was to determine the effects of systemic inflammation induced by peripheral administration of IL-1β on histopathological and behavioral outcome after moderate fluid percussion (FP) brain injury in rats. At 30 min or 24 hr after TBI, saline, 20μg/kg or 40μg/kg of IL-1β was injected (n=4-9/group) intraperitoneally (IP). Sham operated animals (n=9) received either saline or IL-1β (20 or 40 μg/kg) injections. The somatosensory tactile placing test was administered at 1, 2 and 3 days posttrauma. IL-1β treated animals showed significant placing deficits compared to vehicle-treated TBI animals. Three days after injection, contusion areas and volumes were significantly increased (p<0.05) with both IL-1β doses and at both treatment times compared to vehicle treated animals. IL-1β treated rats showed more contusion injury and hippocampal neuronal damage as well as enhanced perivascular neutrophil accumulation. Cortical IL-1r1 mRNA increased as early as 1 hr following TBI, peaking at 24 hr and remained elevated 3 days posttrauma. These data show that the posttraumatic administration of IL-1β significantly aggravates behavioral outcome and increases overall contusion volume after TBI. Increased systemic inflammatory processes, including extravasation of activated leukocytes and proinflammatory cytokines could participate in this detrimental outcome. Because peripherally circulating cytokines and other neurotoxic factors may be increased following multi-organ trauma, these findings may be important in targeting therapeutic interventions in this patient population.

Tetramethylpyrazine reduces blood-brain barrier permeability associated with enhancement of peripheral cholinergic anti-inflammatory effects for treating traumatic brain injury

“…Notably, following TBI, circulating pro-inflammatory cytokines, such as IL-1β and TNF-α, dramatically increased within hours (18). Furthermore, it was reported that intraperitoneal injection of pro-inflammatory cytokines to experimental animals could worsen the pathological consequences of TBI (31). In the present study, plasma levels of IL-1β and TNF-α within 24 h of CCI injury were significantly elevated, and these levels were significantly decreased by TMP.…”

Systemic Inflammation Alters the Kinetics of Cerebrovascular Tight Junction Disruption after Experimental Stroke in Mice

“…These effects are independent of core body and brain temperature (Parry-Jones et al, 2008). Systemic inflammation also sensitizes the brain to neonatal hypoxic and hemorrhagic injury (Lehnardt et al, 2003;Xue and Del Bigio, 2005) and exacerbates excitotoxic (Favrais et al, 2007) and traumatic brain injury (Utagawa et al, 2008). The clinical relevance of these findings is underlined by epidemiological and clinical studies demonstrating that systemic infection is a risk factor for stroke and that preceding infection is associated with less favorable outcome (Emsley and Hopkins, 2008).…”

Perioperative Stroke in Noncardiac, Nonneurosurgical Surgery

“…20,21 It is probable that the acute systemic inflammatory response triggered by surgery initiates or exacerbates ischemic cerebral injury. Laboratory studies using sepsis models in conjunction with neurologic injury 22,23 and clinical studies demonstrate more severe neurologic deficits, especially when preceded by respiratory and urologic infections. 24 -29 Various cytokines have been implicated in the postoperative inflammatory response including interleukin-1, interleukin-6, and tumor necrosis factor ␣, 30 and an increased C-reactive protein level.…”