Brain Inj. 2019;33(3):305-312. doi: 10.1080/02699052.2018.1552988. Epub 2018 Dec 3.

Metal chaperones: a novel therapeutic strategy for brain injury?

Portbury SD¹, Sedjahtera A¹, Perrones K¹, Sgambelloni C¹, Zhang M², Crack PJ², Finkelstein DI¹, Adlard PA^1,3.

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Abstract

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.