Theresa Currier Thomas1, Sarah B Ogle2, Benjamin M Rumney3, Hazel G May4, P David Adelson5, Jonathan Lifshitz6. 1. 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. 2. 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. 3. Department of Biology and Biochemistry, University of Bath, United Kingdom. Electronic address: ben-rumney@ntlworld.com. 4. Department of Biology and Biochemistry, University of Bath, United Kingdom. Electronic address: Hazelmay094@gmail.com. 5. 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. 6. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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 inhumanTBI survivors. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 TBIpatients.
Authors: Diego Iacono; Richard O'Brien; Susan M Resnick; Alan B Zonderman; Olga Pletnikova; Gay Rudow; Yang An; Mark J West; Barbara Crain; Juan C Troncoso Journal: J Neuropathol Exp Neurol Date: 2008-06 Impact factor: 3.685
Authors: Jeffrey R Basford; Li-Shan Chou; Kenton R Kaufman; Robert H Brey; Ann Walker; James F Malec; Anne M Moessner; Allen W Brown Journal: Arch Phys Med Rehabil Date: 2003-03 Impact factor: 3.966
Authors: Patricia B de la Tremblaye; Darik A O'Neil; Megan J LaPorte; Jeffrey P Cheng; Joshua A Beitchman; Theresa Currier Thomas; Corina O Bondi; Anthony E Kline Journal: Neurosci Biobehav Rev Date: 2017-05-30 Impact factor: 8.989
Authors: Saman Sargolzaei; Yan Cai; Melissa J Walker; David A Hovda; Neil G Harris; Christopher C Giza Journal: Annu Int Conf IEEE Eng Med Biol Soc Date: 2018-07
Authors: Katherine R Giordano; L Matthew Law; Jordan Henderson; Rachel K Rowe; Jonathan Lifshitz Journal: Exp Neurobiol Date: 2022-04-30 Impact factor: 3.800
Authors: Benjamin M Aertker; Akshita Kumar; Fanni Cardenas; Franciska Gudenkauf; David Sequeira; Alan R Prossin; Amit K Srivastava; Charles S Cox; Supinder S Bedi Journal: ASN Neuro Date: 2021 Jan-Dec Impact factor: 4.146
Authors: Joshua A Beitchman; Jonathan Lifshitz; Neil G Harris; Theresa Currier Thomas; Audrey D Lafrenaye; Anders Hånell; C Edward Dixon; John T Povlishock; Rachel K Rowe Journal: Neurotrauma Rep Date: 2021-02-08