Temporal window of vulnerability to repetitive experimental concussive brain injury

Luca Longhi, Kathryn E. Saatman, Scott Fujimoto, Ramesh Raghupathi, David F. Meaney, Jason Davis, Asenia McMillan, Valeria Conte, Helmut L. Laurer, Sherman Stein, Nino Stocchetti, Tracy K. McIntosh

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

OBJECTIVE: Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease. MOTHODS: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury. RESULTS: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P <0.05) or mice receiving a single concussion (P <0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P <0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 hours and 1 week after injury in all animals sustaining a single concussion, the occurrence of a second concussion 3 days later resulted in significantly greater traumatic axonal injury (P <0.05) than that resulting from a single CBI. CONCLUSION: These data suggest that a single concussion is associated with behavioral dysfunction and subcellular alterations that may contribute to a transiently vulnerable state during which a second concussion within 3 to 5 days can lead to exacerbated and more prolonged axonal damage and greater behavioral dysfunction.

Original languageEnglish
Pages (from-to)364-373
Number of pages10
JournalNeurosurgery
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 2005

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Brain Injuries
Wounds and Injuries
Brain
Neurodegenerative Diseases
Cognition
Proteolysis
Neurons

Keywords

  • Axonal injury
  • Cognition
  • Concussion
  • Microtubule-associated protein-2
  • Repetitive brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Longhi, L., Saatman, K. E., Fujimoto, S., Raghupathi, R., Meaney, D. F., Davis, J., ... McIntosh, T. K. (2005). Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery, 56(2), 364-373. https://doi.org/10.1227/01.NEU.0000149008.73513.44

Temporal window of vulnerability to repetitive experimental concussive brain injury. / Longhi, Luca; Saatman, Kathryn E.; Fujimoto, Scott; Raghupathi, Ramesh; Meaney, David F.; Davis, Jason; McMillan, Asenia; Conte, Valeria; Laurer, Helmut L.; Stein, Sherman; Stocchetti, Nino; McIntosh, Tracy K.

In: Neurosurgery, Vol. 56, No. 2, 02.2005, p. 364-373.

Research output: Contribution to journalArticle

Longhi, L, Saatman, KE, Fujimoto, S, Raghupathi, R, Meaney, DF, Davis, J, McMillan, A, Conte, V, Laurer, HL, Stein, S, Stocchetti, N & McIntosh, TK 2005, 'Temporal window of vulnerability to repetitive experimental concussive brain injury', Neurosurgery, vol. 56, no. 2, pp. 364-373. https://doi.org/10.1227/01.NEU.0000149008.73513.44
Longhi L, Saatman KE, Fujimoto S, Raghupathi R, Meaney DF, Davis J et al. Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery. 2005 Feb;56(2):364-373. https://doi.org/10.1227/01.NEU.0000149008.73513.44
Longhi, Luca ; Saatman, Kathryn E. ; Fujimoto, Scott ; Raghupathi, Ramesh ; Meaney, David F. ; Davis, Jason ; McMillan, Asenia ; Conte, Valeria ; Laurer, Helmut L. ; Stein, Sherman ; Stocchetti, Nino ; McIntosh, Tracy K. / Temporal window of vulnerability to repetitive experimental concussive brain injury. In: Neurosurgery. 2005 ; Vol. 56, No. 2. pp. 364-373.
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AU - Saatman, Kathryn E.

AU - Fujimoto, Scott

AU - Raghupathi, Ramesh

AU - Meaney, David F.

AU - Davis, Jason

AU - McMillan, Asenia

AU - Conte, Valeria

AU - Laurer, Helmut L.

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N2 - OBJECTIVE: Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease. MOTHODS: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury. RESULTS: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P <0.05) or mice receiving a single concussion (P <0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P <0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 hours and 1 week after injury in all animals sustaining a single concussion, the occurrence of a second concussion 3 days later resulted in significantly greater traumatic axonal injury (P <0.05) than that resulting from a single CBI. CONCLUSION: These data suggest that a single concussion is associated with behavioral dysfunction and subcellular alterations that may contribute to a transiently vulnerable state during which a second concussion within 3 to 5 days can lead to exacerbated and more prolonged axonal damage and greater behavioral dysfunction.

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KW - Cognition

KW - Concussion

KW - Microtubule-associated protein-2

KW - Repetitive brain injury

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