Preclinical Funded Projects

A portion of our budget goes to competitive research proposals that support our scientific mission. We consider research proposals that:

  1. Address military-relevant traumatic brain injury (TBI) and/ or its comorbidities
  2. Exhibit high scientific merit based on potential innovation and impact on the field
  3. Advance and accelerate TBI research that improves recovery of the Warfighter through:
    • fostering collaborative efforts across CNRM investigators
    • leveraging CNRM resources
    • facilitating synergistic efforts with other Military Health System activities

Below are summaries of our active preclinical CNRM funded projects. 

Active Preclinical Funded Projects

Blast Traumatic Brain Injury’s Effect on the Limbic-HPA Axis
Principal InvestigatorJohn T. Wu, Ph.D.
  1. Study the fear-related behavioral outputs associated with limbic regions that regulate the HPA axis
  2. Examine the long-term effect mild TBI has on the HPA axis
  3. Examine the long-term effect mild TBI has on prefrontal cortex neurons and the paraventricular nucleus
Keywords: hypothalamic periventricular nucleus; receptor-like immunoreactivity; corticotrophin-releasing factor; sex-differences; glucocorticoid-receptor

Inhibition of AEA Hydrolysis and Oxidation in Traumatic Brain Injury
Principal InvestigatorYumin Zhang, Ph.D.
Aim: To test the combined effect fatty acid amide hydrolase inhibitors and substrate-selective COX-2 inhibitors have on TBI treatment.
Keywords: PF04457845; cannabinoid receptors; fatty acid amide hydrolase; neuroinflammation; repetitive closed head injury

Meningeal and Neurovascular Responses to Blast-induced Traumatic Brain Injury
Principal InvestigatorJoseph McCabe, Ph.D.
Aim: To examine the relationship among meningeal disruption, opening of the blood brain barrier, and activation of an inflammatory response. Test the effectiveness of an anti-inflammatory compound that might potentially reduce the actions of invading molecules.
Keywords: Blood brain barrier; neuroinflammation; advanced blast simulator; neurodegeneration

Novel N-docosahexaenoylethanolamine Analogues to Improve Traumatic Brain Injury Outcome
Principal InvestigatorHee-Yong Kim, Ph.D.
Aim: To evaluate the cellular bioactivity and pharmacokinetic properties of synaptamide analogues to select bioactive compounds with adequate brain exposure and no toxicity. It will also evaluate the synaptamide analogues’ therapeutic potential by applying them in a repeated Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) mouse model.
Keywords: CHIMERA; docosahexaenoic acid; synaptamide analogues; neuroinflammation; central nervous system

Targeting the Ubiquitin Proteasome System to Develop Treatment for Traumatic Brain Injuries
Principal InvestigatorBarrington Burnett, Ph.D.
  1. To further explores the effect TBI has on proteasome composition and activity in the brain
  2. To assess the effect of inhibiting immunoproteasome activity
Keywords: neuroinflammation; CNS; UPS; neurodegeneration

The Alternate Renin Angiotensin System as a Therapeutic Target for Traumatic Brain Injury
Principal InvestigatorAviva Symes, Ph.D. 
  1. Evaluate if administration of Ang (1-7) at different time points after injury enhances recovery
  2. Determine whether MasR signaling is beneficial to injury recovery
Keywords: animal studies; immunohistochemistry; MRI; receptor mediated change; controlled cortical impact

The Ferret as a Gyrencephalic Model for Traumatic Brain Injury
Principal InvestigatorSharon Juliano, Ph.D.
  1. Determine the optimum timing and number of blast injuries needed to produce the pathological changes indicative of blast injury. These results will be compared to human data.
  2. Evaluate the behavioral changes in ferrets exposed to these blast models
Keywords: advanced blast simulator; repetitive mild TBI; phosphorylated tau; astrogliosis; cognition; motor behavior

The Neural Basis for Post-traumatic Headache and its Link to Anxiety and Depression

Principal InvestigatorAlexander Chesler, Ph.D.

Aim: To functionally dissect the classes of sensory neurons targeting the meninges to better understand the changes they undergo post-injury. It will also determine how these changes affect the neural circuits in the brain and determine the effect these neurons have on headache, anxiety, and depression.

Keywords: headache; migraine; meningeal nociceptors; neural circuits; TBI; depression; anxiety