Long-lasting protection in brain trauma by endotoxin preconditioning

Abstract

We investigated the occurrence of endotoxin (lipopolysaccharide, LPS) preconditioning in traumatic brain injury (TBI), evaluating the time window of LPS-induced protection, its persistence, and the associated molecular mechanisms. Mice received 0.1 mg/kg LPS or saline intraperitoneally and subsequently TBI (by controlled cortical impact brain injury) at various time intervals. Mice receiving LPS 3, 5, or 7 days before TBI showed attenuated motor deficits at 1 week after injury compared with mice receiving saline. Those receiving LPS 5 days before injury had also a reduced contusion volume (7.9±1.3 versus 12±2.3 mm 3 ) and decreased cell death. One month after injury, the protective effect of LPS on contusion volume (14.5 ± 1.2 versus 18.2 ± 1.2 mm 3 ) and neurologic function was still present. Traumatic brain injury increased glial fibrillary acidic protein, CD11b, CD68, tumor necrosis factor-a, interleukin (IL)-10, and IL-6 mRNA expression 24 hours after injury. Lipopolysaccharide administered 5 (but not 9) days before injury increased the expression of CD11b (233%) and of interferon b (500%) in uninjured mice, while it reduced the expression of CD68 (by 46%) and increased that of IL-6 (by 52%) in injured mice. Lipopolysaccharide preconditioning conferred a long-lasting neuroprotection after TBI, which was associated with a modulation of microglia/macrophages activity and cytokine production.

Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma*

“…Mice were anesthetized with intraperitoneal administration of sodium pentobarbital, 65 mg/kg, and placed in a stereotaxic frame. They were subjected to craniectomy followed by induction of CCI brain injury as previously described (23)(24)(25). Our model of injury uses a 3-mm rigid impactor driven by a pneumatic piston, rigidly mounted at an angle of 20°from the vertical plane, and applied perpendicularly to the exposed dura mater over the left parietotemporal cortex at a velocity of 5 m/s and depth of 1 mm.…”

Lipopolysaccharide preconditioning attenuates apoptotic processes and improves neuropathologic changes after spinal cord injury in rats

“…However, it is necessary to investigate endotoxic cross-tolerance in vivo because this phenomenon was initially found in animal experiments and clinical research on humans [20][21][22]. Some authors have described the global or organ-specific features of endotoxic cross-tolerance, as in the lung [23], in blood vessels [24], in the brain [25,26], and in the spinal cord [8,10]. However, LPS preconditioning does not always increase protection; some studies provide different findings compared to the current study.…”

Lipopolysaccharide-Induced Inflammation Aggravates Irradiation-Induced Injury to the Young Mouse Brain

“…It remains to be shown if lower doses of LPS and/or administration at other time points would have different, perhaps even protective, effects after IR. Preconditioning with low doses of LPS before ischemia or traumatic brain injury has been shown to be neuroprotective and to reduce neuroinflammation [32,33,34]. Reduced neuroinflammation after LPS treatment may seem paradoxical, but may simply be secondary to the lesser injury observed.…”