Mesencephalic Astrocyte-Derived Neurotrophic Factor Prevents Traumatic Brain Injury in Rats by Inhibiting Inflammatory Activation and Protecting the Blood-Brain Barrier.
World neurosurgery(2018)
摘要
BACKGROUND:Our previous studies have shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) provides a neuroprotective effect against ischemia/reperfusion injury and is also involved in inflammatory disease models. This study investigates the potential role and mechanism of MANF in acute brain damage after traumatic brain injury (TBI).
METHODS:The model of TBI was induced by Feeney free falling methods with male Sprague-Dawley rats. The expression of MANF, 24 hours after TBI, was detected by the immunohistochemistry, immunofluorescence, Western blot, and reverse transcription polymerase chain reaction techniques. After treatment with recombinant human MANF after TBI, assessment was conducted 24 hours later for brain water content, cerebral edema volume in magnetic resonance imaging, neurobehavioral testing, and Evans blue extravasation. Moreover, by the techniques of Western blot and reverse transcription polymerase chain reaction, the expression of inflammatory cytokines (interleukin 1β and tumor necrosis factor α) and P65 was also analyzed to explore the underlying protective mechanism of MANF.
RESULTS:At 24 hours after TBI, we found that endogenous MANF was widely expressed in the rat's brain tissues and different types of cells. Treatment with a high dose of recombinant human MANF (20 μg/20 μL) significantly increased the modified Garcia score, and reduced brain water content as well as cerebral edema volume on magnetic resonance imaging. Furthermore, MANF alleviated not only the permeability of the blood-brain barrier (BBB) but also the expressions of interleukin 1β and tumor necrosis factor α messenger RNA and protein. Besides, the activation of P65 was also inhibited.
CONCLUSIONS:These results suggest that MANF provides a neuroprotective effect against acute brain injury after TBI, via attenuating blood-brain barrier disruption and intracranial neuroinflammation; the inhibition of the NF-κB signaling pathway might be a potential mechanism.
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