Hartman Lab

Our behavioral neuroscience lab at Loma Linda University in southern California primarily uses animal models of neurological disease to understand their mechanisms and potential therapeutic treatments. Techniques used include behavioral assessment (e.g., water maze) of rats, genetically modified (transgenic/ knockout) mice, and drosophila melanogaster (fruit flies), pharmacology (e.g., manipulation of behavior with various drugs), small animal surgery (e.g., intracardial perfusion, induction of ischemic stroke and/or traumatic brain injury), histology / immunohistochemistry (e.g., visualization of neurons and  Alzheimer’s-like amyloid plaques in brain slices), stereological microscopy (unbiased quantification of brain structures under a microscope), and biochemistry (e.g., protein assays of brain tissue using Western blot and ELISA).

Our lab’s research papers generally fall into 1 of 3 categories: 1) Phenotyping models of neurodegeneration, 2) Treating models of neurodegeneration, and 3) The effects of phytochemicals on the brain. Long-standing collaborations with other labs here (John Zhang, Jiping Tang, Andy Obenaus, Bill Pearce, Denise Bellinger, Larry Longo, and Steve Ashwal) have yielded several publications characterizing rodent models of juvenile and adult brain injury (e.g. traumatic brain injury, stroke, radiation) and treatments for these injuries (monoclonal antibody, polyphenols, stem cells, melatonin, osteopontin, fingomilod, MMP inhibition, DJNK inhibition, hemodilution, and aquaporin-4 RNA interference). Our lab also functions as the Neurobehavioral Core Facility for Loma Linda University’s Center for Brain Hemorrhage Research. The lab’s main interests lie in exploring the interface between acute brain injury (e.g., TBI, stroke, radiation) and subsequent neurodegeneration (e.g., Alzheimer’s neuropathology) and in dissecting the mechanisms by which plant-based compounds (phytochemicals) can influence the brain’s functions under these conditions.

We have shown that traumatic brain injury can accelerate the development of Alzheimer’s-like neuropathology in transgenic mice (Hartman, et al., 2002) and rats (Pop, et al., 2012), and that preventing accumulation of amyloid plaques in their brains with a monoclonal antibody (Hartman, et al., 2005) or dietary phytochemicals (Hartman, et al., 2006) can prevent the age-related decline in cognition seen in these animals. Interestingly, dietary supplementation with pomegranate juice reduced soluble amyloid-β and plaques by ~50% in the brains of transgenic mice, and this was associated with significantly improved cognitive and physical performance.

More importantly, we have shown that administering pomegranate-derived polyphenols improved cognitive and physical performance in humans after heart surgery (Ropacki, et al., 2013) and stroke (Bellone, et al., 2018).

Other experimental data from our lab demonstrates that pomegranate supplementation protected against depression-like behaviors (learned helplessness) induced by radiation exposure (Dulcich & Hartman, 2013) and improved swim speed in transgenic mice (Hartman, et al., 2006). Another phytochemical (resveratrol) was found to improve behavior and neuropathology associated with subarachnoid hemorrhage in rats (Wan, et al., 2018). Presumably, the beneficial effects of  phytochemicals like polyphenols (including the phenolic acids and flavonoids) are mediated by their antioxidant properties and their ability to suppress inflammatory and other pathways.