Preclinical Funded Projects

Preclinical Funded Projects

CNRM has leveraged funding to solicit competitive research proposals in support of our scientific mission. These resources and expertise come together to support the overarching goal of an integrated research program in which preclinical and clinical investigators interact closely, and continuously learn from each other to accelerate research and translation to patient care.
 
We solicit funding opportunity announcements to: 
  1. Address the full spectrum of traumatic brain injury (TBI) with special emphasis on militarily relevant forms of TBI and the concurrent development of post-traumatic stress
  2. Exhibit high scientific merit based on potential innovation and impact on the field
  3. Advance and accelerate TBI research to improve recovery of the Warfighter through:
    • fostering collaborative efforts across CNRM investigators
    • leveraging CNRM resources
    • enabling synergistic efforts with other Military Health System (MHS) activities

Below are summaries of all our active or recently completed preclinical CNRM funded projects. 

Active Preclinical Funded Projects
Name: Blast Traumatic Brain Injury’s Effect on the Limbic-HPA Axis
Principal Investigator: John T. Wu, Ph.D.
Aim:
  • Study the fear-related behavioral outputs associated with limbic regions that regulate the HPA axis
  • Examine the long-term effect mild TBI has on the HPA axis
  • 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
 

Name: Characterization of the Ferret as an Optimal Model to Study the Behavioral, Pathological, and MRI Signatures of Blast Injury
Principal Investigator: Sharon Juliano, Ph.D.
Aim: In a blast injury ferret model, characterize the parameters of the injury to determine how manipulation of blast characteristics affects specific markers of brain injury. Additionally, conduct imaging studies to characterize the evolution of the blast lesion over time with quantitative magnetic resonance imaging (MRI).
Keywords: astrogliosis; advanced blast simulator; diffusion tensor MRI; white matter
 
Name: Development and Characterization of a New Model of Diffuse Traumatic Brain Injury in the Ferret
Principal Investigator: Carlo Pierpaoli, Ph.D.
Aim:
  • Adapt the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model for use in the ferret 
  • Use various in-vivo magnetic resonance imaging (MRI) techniques, longitudinally, to identify imaging biomarkers and to characterize the MRI outcomes of CHIMERA in the ferret
Keywords: CHIMERA; closed head injury models; diffuse axonal injury; in vivo; MRI
 

Name: Induced Pluripotent Stem Cell Tropism and Paracrine Effects in Two Mouse Models of Grey and White Matter Traumatic Brain Injury
Principal Investigator: Martin Doughty, Ph.D.
Aim: To gain in-depth knowledge of human stem cell-derived neurons and astrocytes grafted into two distinct models of TBI in mice:
  1. A grey matter contusion model
  2. A closed-head model of white matter axonal injury
Keywords: RNA-sequencing; astrocyte; human induced pluripotent stem cell; neuron; whole-cell patch-clamp recording
 
Name: Inhibition of AEA Hydrolysis and Oxidation in Traumatic Brain Injury
Principal Investigator: Yumin 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
Publication Link: https://www.ncbi.nlm.nih.gov/pubmed/30526351                                                                   
 

Name: Meningeal and Neurovascular Responses to Blast-induced Traumatic Brain Injury
Principal Investigator: Joseph 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
Publication Link: There are no publications related to this project at this time
 

Name: Myelin Plasticity in the Progression of White Matter Pathology in Traumatic Brain Injury
Principal Investigator: Regina Armstrong, Ph.D.  
Aim:
  • Characterize myelin plasticity after TBI
  • Differentiate the contribution of myelin remodeling to the progression of pathology after TBI
Keywords: axon damage; myelin; nerve conduction; node of Ranvier; paranode
 

Name: Novel N-docosahexaenoylethanolamine Analogues to Improve Traumatic Brain Injury Outcome
Principal Investigator: Hee-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
Publication Link: There are no publications related to this project at this time
 

Principal Investigator: Brian Cox, Ph.D.
Aim: To evaluate blood lipid profiles from well-characterized TBI subjects and compares the lipid profiles with non-TBI controls.
Keywords: central nervous system; TBI; blood based biomarkers
Publication Link: There are no publications related to this project at this time
 

Name: Quantitative Magnetic Resonance Imaging Biomarkers of the Effects of Omega-3 Fatty Acids Therapy in Traumatic Brain Injury
Principal Investigator: Carlo Pierpaoli, Ph.D.
Aim: To evaluate the effect omega-3 fatty acid supplements, such as docosahexaenoic acid (DHA), has on TBI recovery.
Keywords: docosahexaenoic acid; controlled cortical impact; diffusion MRI; diffusion tensor imaging
Publication Link: There are no publications related to this project at this time
 

Name: Targeting the Ubiquitin Proteasome System to Develop Treatment for Traumatic Brain Injuries
Principal Investigator: Barrington Burnett, Ph.D.
Aim:
  • To further explores the effect TBI has on proteasome composition and activity in the brain
  • To assess the effect of inhibiting immunoproteasome activity
Keywords: neuroinflammation; CNS; UPS; neurodegeneration
Publication Link: There are no publications related to this project at this time
 

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

Name: The Ferret as a Gyrencephalic Model for Traumatic Brain Injury
Principal Investigator: Sharon Juliano, Ph.D.
Aim:
  • 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.
  • Evaluate the behavioral changes in ferrets exposed to these blast models
Keywords: advanced blast simulator; repetitive mild TBI; phosphorylated tau; astrogliosis; cognition; motor behavior
 

Name: The Neural Basis for Post-Traumatic Headache and its Link to Anxiety and Depression
Principal Investigator: Alexander 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
Publication Link: There are no publications related to this project at this time