Aviva J. Symes, Ph.D.

Aviva J. Symes, Ph.D.

Aviva Symes

Name: Aviva J. Symes, Ph.D.

Department of Primary Appointment: Pharmacology
Position: USU Faculty
Title: Professor

Affiliated Departments: Molecular & Cell Biology,
Affiliated Center: CNRM

Research Interests:
Neuroinflammatory changes after traumatic brain injury

Office Phone: (301) 295-3234
Fax Number: (301) 295-3220
Room: C2126

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PubMed Listing

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  • Ph.D. Biochemistry, University College London, UK
  • Postdoctoral Fellowship: Neurology, Massachusetts General Hospital/ Harvard Medical School

Research Interests:

Our lab aims to understand the mechanisms through which the brain responds to traumatic injury and more specifically to delineate the pathways through which detrimental neuroinflammatory cascades can be altered to enhance recovery after injury. The initial lesion can produce significant tissue damage and breakdown of the blood brain barrier. These immediate effects lead to activation of many secondary cascades involving interplay between endogenous surviving neurons and glia, and infiltrating cells and molecules from the bloodstream. Injury therefore leads to acute neuroinflammatory cascades, and also to more chronic inflammatory effects.  Indeed, activated microglia have been documented in postmortem brains many years after the initial insult. Our lab focuses on understanding the molecular signaling cascades that occur after injury in addition to testing potential therapeutics to enhance recovery from injury. We currently utilize several different rodent models of traumatic brain injury (TBI), with assays ranging from behavioral through molecular to understand the complex interactions that occur after injury, and to determine how manipulations may impact on functional recovery. We also utilize primary cell cultures to tease apart the molecular signaling pathways that contribute to inflammation after injury.

GFAP and collagen

TGF-β signaling after injury

TGF-β is an injury induced cytokine that has complex roles in the central nervous system. After brain injury TGF-β can promote astrogliosis and enhance the deposition of molecules inhibitory to regeneration in the glial scar. Yet TGF-β is also neuroprotective indicating the sometimes conflicting roles of this cytokine. We have shown that after a penetrating brain injury mice that lack expression of the TGF-β signaling molecule Smad3, form a glial scar more quickly, with a smaller scar, than wild type mice. However, we also found that Smad3 null mice have more pronounced neuronal loss after injury. Thus, global interference with TGF-β signaling is not a desirable therapeutic option. Further, TGF-β is anti-inflammatory in some contexts – so chronic repression of TGF-β signaling pathways may enhance inflammation. In primary microglial cultures we have shown that inflammatory pathways downregulate TGF-β receptor expression, allowing for prolonged enhancement of the inflammatory activated state.

Angiotensin receptor blockers as potential therapeutics for TBI

Angiotensin receptor blockers (ARBs) are widely used FDA-approved anti-hypertension drugs with a favorable side effect profile that have been used as a mechanism for reducing the amount of TGF-β signaling in several different organ systems. In the CNS, ARBs have also been shown to be neuroprotective, anti-inflammatory and protective of the cerebral blood flow (CBF). The brain possesses its own renin angiotensin system, with many different components of the system expressed in the different cell types in the brain. However, in addition to acting as antagonists at the Angiotensin II receptor 1 (AT1R) some ARBs also possess potent PPARγ agonist activity that enhances their anti-inflammatory action. We have demonstrated that the ARB candesartan, lessens inflammation, reduces lesion volume, limits glial reactivity, increases neuronal survival and improves motor and cognitive recovery up to 28 days after injury. These beneficial effects are seen when low-dose candesartan is administered up to 6 hours after injury, a clinically acceptable therapeutic window. Our data suggest that both AT1 receptor antagonism and PPARγ agonism contribute to the efficacy of ARB treatment after TBI and it is this multimodal action by a single drug that makes it a strong candidate for TBI clinical trials. We are pursuing translational studies for candesartan for brain injury in addition to investigating the consequences of TBI on the endogenous renin-angiotensin system in the brain.

Brain Scan