title: Does time heal all wounds? Experimental diffuse traumatic brain injury results in persisting histopathology in the thalamus.
abstract: Thalamic dysfunction has been implicated in overall chronic neurological dysfunction after traumatic brain injury (TBI), however little is known about the underlying histopathology. In experimental diffuse TBI (dTBI), we hypothesize that persisting histopathological changes in the ventral posteromedial (VPM) nucleus of the thalamus is indicative of progressive circuit reorganization. Since circuit reorganization in the VPM impacts the whisker sensory system, the histopathology could explain the development of hypersensitivity to whisker stimulation by 28days post-injury; similar to light and sound hypersensitivity in human TBI survivors.
  
  
  
  Adult, male Sprague-Dawley rats underwent craniotomy and midline fluid percussion injury (FPI) (moderate severity; 1.8-2.0atm) or sham surgery. At 1d, 7d, and 28days post-FPI (d FPI) separate experiments confirmed the cytoarchitecture (Giemsa stain) and evaluated neuropathology (silver stain), activated astrocytes (GFAP), neuron morphology (Golgi stain) and microglial morphology (Iba-1) in the VPM.
  
  
  
  Cytoarchitecture was unchanged throughout the time course, similar to previously published data; however, neuropathology and astrocyte activation were significantly increased at 7d and 28d and activated microglia were present at all time points. Neuron morphology was dynamic over the time course with decreased dendritic complexity (fewer branch points; decreased length of processes) at 7d FPI and return to sham values by 28d FPI.
  
  
  
  These data indicate that dTBI results in persisting thalamic histopathology out to a chronic time point. While these changes can be indicative of either adaptive (recovery) or maladaptive (neurological dysfunction) circuit reorganization, they also provide a potential mechanism by which maladaptive circuit reorganization could contribute to the development of chronic neurological dysfunction. Understanding the processes that mediate circuit reorganization is critical to the development of future therapies for TBI patients.
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Phoenix VA Health Care System, Phoenix, AZ, USA. Electronic address: theresathomas@email.arizona.edu.
authors.forename: Theresa Currier
authors.initials: TC
authors.lastname: Thomas
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Phoenix Integrated Surgical Residency, Banner University Medical Center, Phoenix, AZ, USA; Department of Surgery, Banner University Medical Center, Phoenix, AZ, USA. Electronic address: sogle@email.arizona.edu.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Ogle
authors.affiliation: Department of Biology and Biochemistry, University of Bath, United Kingdom. Electronic address: ben-rumney@ntlworld.com.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Rumney
authors.affiliation: Department of Biology and Biochemistry, University of Bath, United Kingdom. Electronic address: Hazelmay094@gmail.com.
authors.forename: Hazel G
authors.initials: HG
authors.lastname: May
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Neuroscience Program, Arizona State University, Tempe, AZ, USA; School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA. Electronic address: dadelson@phoenixchildrens.com.
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Phoenix VA Health Care System, Phoenix, AZ, USA; Neuroscience Program, Arizona State University, Tempe, AZ, USA. Electronic address: jlifshitz@email.arizona.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lifshitz
mesh_terms: D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D000070642:Brain Injuries, Traumatic / Q000473:pathology* / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009473:Neuronal Plasticity; D009474:Neurons / Q000473:pathology / Q000502:physiology; D017207:Rats, Sprague-Dawley; D016622:Silver Staining; D013788:Thalamus / Q000293:injuries* / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
keywords: Post-concussive symptoms; Somatosensory; Thalamus; Traumatic brain injury; Whisker-circuit