Brain injury · 2018
Metal chaperones: a novel therapeutic strategy for brain injury?
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Portbury S D, Sedjahtera A, Perrones K, Sgambelloni C, Zhang M, Crack P J, Finkelstein D I, Adlard P A
Аннотация
OBJECTIVE: This study sought to assess the potential efficacy of a novel class of metal chaperone on the outcomes in an animal model of a controlled cortical impact. This work was predicated on previous observations that this class of compound has exhibited neuroprotective potential in other models of aging and neurodegeneration.
RESEARCH DESIGN: The study employed a controlled cortical impact traumatic brain injury in three month old mice with subsequent behavioral and cellular assessments to determine therapeutic efficacy.
METHODS: Cognitive (Y-maze) and motor assessments (Rotarod and Open Field) were employed to determine behavioral end points. Histological-based methods were utilized to assess neuronal integrity, astrocytosis, and lesion volume.
OUTCOMES: We demonstrate here that acute post-injury treatment with PBT2 (Prana Biotechnology) is sufficient to maintain neuronal integrity (evidenced by decreased lesion area and increased numbers of neurons; decreased astrocytosis was also present) and to normalize performance in cognitive testing (Y-maze). These effects occurred within days and were maintained for the entire duration of the study (26 days post-injury). These data support the further interrogation of the utility of metal chaperones for the treatment and/or prevention of the neuroanatomical, biochemical, and behavioral deficits that occur following brain injuries of different etiologies.
RESEARCH DESIGN: The study employed a controlled cortical impact traumatic brain injury in three month old mice with subsequent behavioral and cellular assessments to determine therapeutic efficacy.
METHODS: Cognitive (Y-maze) and motor assessments (Rotarod and Open Field) were employed to determine behavioral end points. Histological-based methods were utilized to assess neuronal integrity, astrocytosis, and lesion volume.
OUTCOMES: We demonstrate here that acute post-injury treatment with PBT2 (Prana Biotechnology) is sufficient to maintain neuronal integrity (evidenced by decreased lesion area and increased numbers of neurons; decreased astrocytosis was also present) and to normalize performance in cognitive testing (Y-maze). These effects occurred within days and were maintained for the entire duration of the study (26 days post-injury). These data support the further interrogation of the utility of metal chaperones for the treatment and/or prevention of the neuroanatomical, biochemical, and behavioral deficits that occur following brain injuries of different etiologies.