Hartman Lab

The Hartman behavioral neuroscience lab at Loma Linda University, an R2 health-sciences institute in southern California, primarily uses animal models (rats, transgenic/ knockout mice, and drosophila melanogaster [fruit flies]) of neurological disease to understand their mechanisms and potential therapeutic treatments. Techniques used include behavioral assessment (e.g., water maze), psychopharmacology (e.g., manipulation of behavior with drugs), surgery (e.g., induction of stroke and/or traumatic brain injury), histology / immunohistochemistry (e.g., visualization of neurons, white matter, proteins, amyloid plaques, etc. 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, ELISA, etc.).

Long-standing collaborations and multiple intra- and extra-mural grants (LLU, NASA, NINDS, NICHD, DOD, NRSA, California Table Grape Commission) have yielded over 70 publications characterizing rodent models of juvenile and adult neurodegeneration (traumatic brain injury, stroke, radiation, exposure to anesthesia, Alzheimer’s disease) and treatments for these nervous system insults (e.g., monoclonal antibodies, polyphenols, stem cells, melatonin, osteopontin, fingomilod, MMP inhibition, DJNK inhibition, hemodilution, glucocorticoids, and aquaporin-4 RNA interference). We also function as the Neurobehavioral Core Facility for Loma Linda University’s Center for Brain Hemorrhage Research.

Our lab’s research is broadly concerned with promoting healthy brain aging / increasing an individual’s “health-span”, and generally falls into 1 of 3 overlapping categories: 1) Characterizing models of neurodegeneration, 2) Preventing neurodegeneration and/or increasing the brain’s resiliency, and 3) Characterizing the effects of plant-based compounds (phytochemicals) in the brain. Our main interests lie in exploring the interface between acute and/or chronic brain injury (e.g., TBI, stroke, radiation) and subsequent neurodegeneration (e.g., Alzheimer’s, chronic traumatic encephalopathy) and in dissecting the mechanisms by which phytochemicals (e.g., polyphenols) and other interventions can influence the brain’s recovery and function under these conditions.

We have shown that traumatic brain injury can accelerate the development of Alzheimer’s- like neuropathology in rodents (Hartman, et al., 2002; Pop, et al., 2012) and that preventing accumulation of amyloid plaques in their brains with a monoclonal antibody or dietary phytochemicals can prevent the age-related decline in cognition seen in these animals (Hartman, et al., 2005; Hartman, et al., 2006). 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. We have also published data showing that exercise and ellagic acid (a polyphenolic component of pomegranates) improved motor performance, learning ability, and lifespan in a transgenic fruit fly model of Alzheimer’s disease (Morgan, et al., 2025). Other experimental data from our lab demonstrates that pomegranate supplementation protected against depression-like behaviors (learned helplessness) induced by radiation exposure (Dulcich & Hartman, 2013). Another phytochemical (resveratrol) was found to improve behavior and neuropathology associated with subarachnoid hemorrhage in rats (Wan, et al., 2018).

More importantly, we have conducted randomized clinical trials in humans showing that administering pomegranate-derived polyphenols improved cognitive and physical performance after heart surgery (Ropacki, et al., 2013) and stroke (Bellone, et al., 2018). We have also published a retrospective analysis of data suggesting that symptoms of depression associated with adverse childhood events may be ameliorated by a flavonoid-rich diet (Tan, et al., 2020). Presumably, the beneficial effects of polyphenols (including the phenolic acids and flavonoids) are mediated by their ability to suppress inflammatory pathways and activate antioxidant pathways.

More recently, we have begun to look at other measures of brain resiliency such as cortical entropy within human EEG, and we have recently published a paper showing that individuals with bipolar disorder have higher baseline cortical entropy but reduced entropy modulation in response to an auditory stimulus (Creel, et al., in press).

(views and opinions expressed do not necessarily reflect policies or positions of LLUH)