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 journalArticle

25 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)8-19
Number of pages12
JournalExperimental Neurology
Volume234
Issue number1
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Substantia Nigra
Dopamine
Wounds and Injuries
Blood Vessels
Dementia
Percussion
Neurons
Tyrosine 3-Monooxygenase
Parkinsonian Disorders
Ataxia
Diffuse Brain Injury
Craniocerebral Trauma
Silver
Athletes
Brain Injuries
Atrophy
Sports
Sprague Dawley Rats
Coloring Agents
Pathology

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat. / Van Bregt, Daniel R.; Thomas, Theresa Currier; Hinzman, Jason M.; Cao, Tuoxin; Liu, Mei; Bing, Guoying; Gerhardt, Greg A.; Pauly, James R.; Lifshitz, Jonathan.

In: Experimental Neurology, Vol. 234, No. 1, 03.2012, p. 8-19.

Research output: Contribution to journalArticle

Van Bregt, DR, Thomas, TC, Hinzman, JM, Cao, T, Liu, M, Bing, G, Gerhardt, GA, Pauly, JR & Lifshitz, J 2012, 'Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat', Experimental Neurology, vol. 234, no. 1, pp. 8-19. https://doi.org/10.1016/j.expneurol.2011.12.003
Van Bregt, Daniel R. ; Thomas, Theresa Currier ; Hinzman, Jason M. ; Cao, Tuoxin ; Liu, Mei ; Bing, Guoying ; Gerhardt, Greg A. ; Pauly, James R. ; Lifshitz, Jonathan. / Substantia nigra vulnerability after a single moderate diffuse brain injury in the rat. In: Experimental Neurology. 2012 ; Vol. 234, No. 1. pp. 8-19.
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