Single low-dose lipopolysaccharide preconditioning: neuroprotective against axonal injury and modulates glial cells.
OBJECTIVE
Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection. However, the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains unclear.


METHODS
The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight drop. LPS was administered 7 days prior to TBI. LPS administration reduced locomotion, which recovered completely by time of injury.


RESULTS
LPS preconditioning significantly reduced the post-injury gliosis response near the corpus callosum, possibly by downregulating the oncostatin M receptor. These novel findings demonstrate a protective role of LPS preconditioning against diffuse axonal injury. LPS preconditioning successfully prevented neurodegeneration near the corpus callosum, as measured by fluorojade B.


CONCLUSIONS
Further work is required to elucidate whether LPS preconditioning confers long-term protection against behavioral deficits and to elucidate the biochemical mechanisms responsible for LPS-induced neuroprotective effects.
Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA.
Ryan C
RC
Turner
Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA.
Zachary J
ZJ
Naser
Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA.
Brandon P
BP
Lucke-Wold
Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, WV 26506, USA.
Aric F
AF
Logsdon
Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Center for Health Restoration, West Virginia University, School of Nursing, Morgantown, WV 26506, USA.
Reyna L
RL
Vangilder
Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, WV 26506, USA.
Rae R
RR
Matsumoto
Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, WV 26506, USA.
Jason D
JD
Huber
Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV 26506, USA; Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV 26506, USA.
Charles L
CL
Rosen
Lipopolysaccharide preconditioning; diffuse axonal injury; gliosis; neuroprotection; oncostatin M receptor