A concussive-like brain injury model in mice (I)

Impairment in learning and memory

Ya Ping Tang, Yukihiro Noda, Takaaki Hasegawa, Toshitaka Nabeshima

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The modeling of human concussive brain injury (CBI) in the laboratory has been challenging. In the present study, we developed an experimental CBI model in mice using a novel weight-drop device. Various injury levels were examined by adjusting the height of the falling weight (diameter 10 mm, length 20 cm, weight 21 g). At a height of 50 cm, the impact resulted in a mortality rate of 46.7% with a skull fracture rate of 28.6%. At a height of 25 cm, however, the impact produced a concussive-like brain injury (CLBI) to the mice without skull fracture. A series of pathophysiological and neurobehavioral responses was evaluated at this injury level. The CLBI mice lost muscle tone and righting reflex response immediately following the trauma and recovered from the latter within a short duration of 1.6 ± 0.32 min (mean ± SE). Brain edema formation started at 12 h, reached a maximum at 24 h and recovered 48 h. Typically edema was found in the neocortex, hippocampus, and cerebellum, but not in the brain stem. Deficits in the feeding behaviors lasted for 2 days, accompanied by lower body weight persisting for 5 days. The body weight growth rate for 24 h returned to the control levels by the third day postinjury. Learning and memory were evaluated at the end of 1-3 weeks after the trauma using a water-finding task. At I week, exploratory behaviors were slightly inhibited while learning and memory were profoundly impaired. Interestingly, the learning and memory deficits lasted for 2 weeks while recovering to the control levels by 3 weeks. No motor disability was found in the CLBI mice during the 3-week evaluations. These results indicate that the weight-drop impact produced graded injury to the brain, and at the injury level of 25 cm it produced a CLBI in the mice in which the characteristics of transient loss of neurobehavioral responses, short duration of brain edema, and long-lasting learning and memory deficits are similar to those of human CBI.

Original languageEnglish
Pages (from-to)851-862
Number of pages12
JournalJournal of Neurotrauma
Volume14
Issue number11
DOIs
Publication statusPublished - 01-01-1997
Externally publishedYes

Fingerprint

Brain Injuries
Learning
Righting Reflex
Wounds and Injuries
Skull Fractures
Weights and Measures
Brain Edema
Memory Disorders
Accidental Falls
Body Weight
Exploratory Behavior
Neocortex
Feeding Behavior
Cerebellum
Brain Stem
Hippocampus
Edema
Equipment and Supplies
Muscles
Mortality

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Tang, Ya Ping ; Noda, Yukihiro ; Hasegawa, Takaaki ; Nabeshima, Toshitaka. / A concussive-like brain injury model in mice (I) : Impairment in learning and memory. In: Journal of Neurotrauma. 1997 ; Vol. 14, No. 11. pp. 851-862.
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abstract = "The modeling of human concussive brain injury (CBI) in the laboratory has been challenging. In the present study, we developed an experimental CBI model in mice using a novel weight-drop device. Various injury levels were examined by adjusting the height of the falling weight (diameter 10 mm, length 20 cm, weight 21 g). At a height of 50 cm, the impact resulted in a mortality rate of 46.7{\%} with a skull fracture rate of 28.6{\%}. At a height of 25 cm, however, the impact produced a concussive-like brain injury (CLBI) to the mice without skull fracture. A series of pathophysiological and neurobehavioral responses was evaluated at this injury level. The CLBI mice lost muscle tone and righting reflex response immediately following the trauma and recovered from the latter within a short duration of 1.6 ± 0.32 min (mean ± SE). Brain edema formation started at 12 h, reached a maximum at 24 h and recovered 48 h. Typically edema was found in the neocortex, hippocampus, and cerebellum, but not in the brain stem. Deficits in the feeding behaviors lasted for 2 days, accompanied by lower body weight persisting for 5 days. The body weight growth rate for 24 h returned to the control levels by the third day postinjury. Learning and memory were evaluated at the end of 1-3 weeks after the trauma using a water-finding task. At I week, exploratory behaviors were slightly inhibited while learning and memory were profoundly impaired. Interestingly, the learning and memory deficits lasted for 2 weeks while recovering to the control levels by 3 weeks. No motor disability was found in the CLBI mice during the 3-week evaluations. These results indicate that the weight-drop impact produced graded injury to the brain, and at the injury level of 25 cm it produced a CLBI in the mice in which the characteristics of transient loss of neurobehavioral responses, short duration of brain edema, and long-lasting learning and memory deficits are similar to those of human CBI.",
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A concussive-like brain injury model in mice (I) : Impairment in learning and memory. / Tang, Ya Ping; Noda, Yukihiro; Hasegawa, Takaaki; Nabeshima, Toshitaka.

In: Journal of Neurotrauma, Vol. 14, No. 11, 01.01.1997, p. 851-862.

Research output: Contribution to journalArticle

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