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2017 ; 12
(8
): e0183683
Nephropedia Template TP
Portbury SD
; Hare DJ
; Finkelstein DI
; Adlard PA
PLoS One
2017[]; 12
(8
): e0183683
PMID28837626
show ga
Traumatic brain Injury (TBI) is a significant cause of death and long-term
disability for which there are currently no effective pharmacological treatment
options. In this study then, we utilized a mouse model of TBI to assess the
therapeutic potential of the stable disaccharide trehalose, which is known to
protect against oxidative stress, increase levels of chaperone molecules and
enhance autophagy. Furthermore, trehalose has demonstrated neuroprotective
properties in numerous animal models and has been proposed as a potential
treatment for neurodegeneration. As TBI (and associated neurodegenerative
disorders) is complicated by a sudden and dramatic change in brain metal
concentrations, including iron (Fe) and zinc (Zn), the collective accumulation
and translocation of which has been hypothesized to contribute to the
pathogenesis of TBI, then we also sought to determine whether trehalose modulated
the metal dyshomeostasis associated with TBI. In this study three-month-old
C57Bl/6 wildtype mice received a controlled cortical impact TBI, and were
subsequently treated for one month with trehalose. During this time animals were
assessed on multiple behavioral tasks prior to tissue collection. Results showed
an overall significant improvement in the Morris water maze, Y-maze and open
field behavioral tests in trehalose-treated mice when compared to controls. These
functional benefits occurred in the absence of any change in lesion volume or any
significant modulation of biometals, as assessed by laser ablation inductively
coupled plasma mass spectrometry. Western blot analysis, however, revealed an
upregulation of synaptophysin, doublecortin and brain derived neurotrophic factor
protein in trehalose treated mice in the contralateral cortex. These results
indicate that trehalose may be efficacious in improving functional outcomes
following TBI by a previously undescribed mechanism of action that has relevance
to multiple disorders of the central nervous system.
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