Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat

Daniel R. Van Bregt, Theresa Currier Thomas, Jason M. Hinzman, Tuoxin Cao, Mei Liu, Guoying Bing, Greg A. Gerhardt, James R. Pauly, Jonathan Lifshitz

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Dementia and parkinsonism are late-onset symptoms associated with repetitive head injury, as documented in multiple contact-sport athletes. Clinical symptomatology is the likely phenotype of chronic degeneration and circuit disruption in the substantia nigra (SN). To investigate the initiating neuropathology, we hypothesize that a single diffuse brain injury is sufficient to initiate SN neuropathology including neuronal loss, vascular disruption and microglial activation, contributing to neurodegeneration and altered dopamine regulation. Adult, male Sprague-Dawley rats were subjected to sham or moderate midline fluid percussion brain injury. Stereological estimates indicated a significant 44% loss of the estimated total neuron number in the SN at 28-days post-injury, without atrophy of neuronal nuclear volumes, including 25% loss of tyrosine hydroxylase positive neurons by 28-days post-injury. Multi-focal vascular compromise occurred 1-2. days post-injury, with ensuing microglial activation (significant 40% increase at 4-days). Neurodegeneration (silver-stain technique) encompassed on average 21% of the SN by 7-days post-injury and increased to 29% by 28-days compared to sham (1%). Whole tissue SN, but not striatum, dopamine metabolism was altered at 28-days post-injury, without appreciable gene or protein changes in dopamine synthesis or regulation elements. Together, single moderate diffuse brain injury resulted in SN neurovascular pathology potentially associated with neuroinflammation or dopamine dysregulation. Compensatory mechanisms may preserve dopamine signaling acutely, but subsequent SN damage with aging or additional injury may expose clinical symptomatology of motor ataxias and dementia. andcopy; 2011 Elsevier Inc.

Original languageEnglish
Pages (from-to)8-19
Number of pages12
JournalExperimental Neurology
Issue number1
StatePublished - Mar 2012

Bibliographical note

Funding Information:
With generous thanks to Amanda Lisembee, Deanne Hopkins, Kelley Hall and Stewart Surgener without whose technical expertise and insightful support this study would not have been possible. Supported, in part, by University of Kentucky College of Medicine , NIH NINDS R01 NS065052 , NIH NIA T32 AG000242 , NIH NINDS F31 NS067899 , Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT) 7-11, KSCHIRT 11-2a, NIH P50 NS039787 and NIH NINDS P30 NS051220 .


  • Brain injury
  • Concussion
  • PCR
  • Parkinsons
  • Substantia nigra

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


Dive into the research topics of 'Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat'. Together they form a unique fingerprint.

Cite this