Aswathi Kumar, Deborah Kennedy- Boone, Harris A Weisz, Bridget A Capra, Tatsuo Uchida, Kristofer Jennings, Maria-Adelaide Micci, Margaret Parsley, Douglas S DeWitt, Donald S. Prough and Helen L Hellmich
Aframomum melegueta is an herb in the ginger family that has been shown to have anti-inflammatory, antioxidative, anti-diabetic and antimicrobial properties. We investigated the possibility that the seeds of this herb, which are consumed by gorillas and used as a spice in West and North African cuisine, could have neuroprotective effects in a rat model of traumatic brain injury (TBI). Using Fluoro-Jade, an anionic fluorescent stain that is a well-established marker of degenerating neurons, we found that an extract of Aframomum, PMI-006, significantly reduced numbers of dying, Fluoro-Jade-positive neurons in the rat hippocampus 24 hr after TBI. We used an antibody to CD11b (Ox42), a microglial marker, to show that PMI almost completely reduced microglial activation-a hallmark of injury-induced inflammation- in the rat hippocampus and cortex. To elucidate the molecular mechanisms underlying the neuro protective effects of PMI-006, we used RT2 Profiler pathway-focused PCR arrays representing oxidative stress, cytokine & chemokines and NFκB cell signaling pathways to interrogate PMI-induced changes in hippocampal gene expression after TBI. We found that PMI treatment ameliorated the effects of brain injury and, in several cases, restored injuryinduced gene expression changes to sham control levels. PMI treatment did not significantly alter functional outcome in the Morris Water Maze, a neurobehavioral test of hippocampal-dependent spatial memory. However, because of its safety profile and because it mitigates the effects of TBI on stress and inflammatory signaling pathways that are associated with TBI pathology, PMI could be potentially beneficial in reducing neurodegeneration in TBI survivors.