Metal chaperones: a novel therapeutic strategy for brain injury?

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.