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Turner et al. LPS preconditioning neuroprotective

Figure 6: Colocalization of GFAP and OSMR with DAPI. GFAP (green) and OSMR (red) were significantly increased in the same cells
(merged yellow) following TBI. LPS preconditioning prevented OSMR upregulation. *P < 0.05. LPS: lipopolysaccharide; TBI: traumatic brain
injuries; GFAP: glial fibrillary acidic protein; OSMR: oncostatin M receptor
the same astrocyte. This was partially mitigated by closed-head model of diffuse axonal injury. LPS
LPS preconditioning (overlap coefficient r = 0.478). preconditioning has previously been shown to be
protective in penetrating models, but there was
DISCUSSION significant vascular disruption in these models and
they were generally more severe than our model
Diffuse axonal injury is induced consistently by the of diffuse axonal injury. The findings of the present
weight drop method without producing a grossly study are significant in that they demonstrate that
visible lesion. [23] We have previously confirmed that LPS preconditioning regulates microglia and OSMR
the injury parameters used in this study induce in a model of diffuse axonal injury. Furthermore,
diffuse axonal injury by measuring β-amyloid these protective effects are sustained at one week
precursor protein expression. [24] The weight drop post-injury. Protection was established in a mild
model is ideal for testing neuroprotective strategies injury model with no mortality or gross pathological
because it induces consistent axonal damage and a changes, indicating that LPS pretreatment may also
protect against mild neurotrauma.
characteristic progression of traumatic axonal injury in
rodents. [25] Axonal injury reduces cerebral blood flow Longhi et al. showed that LPS preconditioning
[2]
following neurotrauma. [26] Therefore, it is potentially alters IL-6 and OSM expression following TBI. In
worthwhile to investigate compounds that contribute this study, we demonstrated that LPS may exert a
to vascular preconditioning. Vascular preconditioning neuroprotective effect against diffuse axonal injury
by heat activation reduces TBI severity and the extent through modulation of neurodegeneration and the
of axonal damage by selectively activating hypoxia- gliosis response. This supports the notion that LPS
inducible factor 1α. [27] Low-dose LPS pretreatment induces neuroprotective effects originally proposed
has also been used for successful vascular by Longhi et al. We observed a transient acute
[2]
preconditioning in penetrating models of TBI. [28] sickness induced by LPS pretreatment. However,
One proposed mechanism for LPS is a reduction of LPS preconditioning had the following effects,
inflammatory mediators before injury. [29] Inflammatory including: reduced FJB, OSMR, GFAP, and CD68
mediators can activate gliosis. [30] expression. Decreased FJB staining was indicative
of reduced neurodegeneration. This has been
In this study, we show for the first time that low- demonstrated in vitro by Zhu et al., [31] and our
dose LPS preconditioning is protective in a findings have now confirmed this in vivo. Increased
12 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ January 20, 2017