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A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice.

Chen Y, Mao H, Yang KH, Abel T, Meaney DF - Front Neurol (2014)

Bottom Line: Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury.Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively.Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Pennsylvania , Philadelphia, PA , USA.

ABSTRACT
For the past 25 years, controlled cortical impact (CCI) has been a useful tool in traumatic brain injury (TBI) research, creating injury patterns that includes primary contusion, neuronal loss, and traumatic axonal damage. However, when CCI was first developed, very little was known on the underlying biomechanics of mild TBI. This paper uses information generated from recent computational models of mild TBI in humans to alter CCI and better reflect the biomechanical conditions of mild TBI. Using a finite element model of CCI in the mouse, we adjusted three primary features of CCI: the speed of the impact to achieve strain rates within the range associated with mild TBI, the shape, and material of the impounder to minimize strain concentrations in the brain, and the impact depth to control the peak deformation that occurred in the cortex and hippocampus. For these modified cortical impact conditions, we observed peak strains and strain rates throughout the brain were significantly reduced and consistent with estimated strains and strain rates observed in human mild TBI. We saw breakdown of the blood-brain barrier but no primary hemorrhage. Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury. Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively. Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

No MeSH data available.


Related in: MedlinePlus

Mild controlled cortical impact leads to a transient behavioral impairment. A behavioral testing paradigm to examine both cortical and hippocampal function after impact is shown in (A). Rotarod (RR) training occurred the day before injury; RR was given on days 1–3 post injury. Spatial object recognition (SOR) was implemented on days 4 (training) and 5 (test day). Contextual fear conditioning (CFC) was given on days 7 (training) and 8 (test). The animals were perfused on day 8 after CFC. The rotarod results (B) indicate injured animals faulted at lower speeds with significantly lower fault and fall latency times as determine by a repeated measures ANOVA (p = 0.0009 and 0.0017, respectively). In neither the SOR (C) nor the CFC (D) (p = 0.2345, p = 0.2182, respectively) did injured mice show significant level of altered behavior. Sample size n = 17 sham, n = 19 injured. Data are expressed as media ± SEM.
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Figure 9: Mild controlled cortical impact leads to a transient behavioral impairment. A behavioral testing paradigm to examine both cortical and hippocampal function after impact is shown in (A). Rotarod (RR) training occurred the day before injury; RR was given on days 1–3 post injury. Spatial object recognition (SOR) was implemented on days 4 (training) and 5 (test day). Contextual fear conditioning (CFC) was given on days 7 (training) and 8 (test). The animals were perfused on day 8 after CFC. The rotarod results (B) indicate injured animals faulted at lower speeds with significantly lower fault and fall latency times as determine by a repeated measures ANOVA (p = 0.0009 and 0.0017, respectively). In neither the SOR (C) nor the CFC (D) (p = 0.2345, p = 0.2182, respectively) did injured mice show significant level of altered behavior. Sample size n = 17 sham, n = 19 injured. Data are expressed as media ± SEM.

Mentions: In all, mCCI produced very mild early behavioral deficits (Figure 9A). Injured mice showed vestibulomotor impairment after injury, as evident through the rotarod testing results. In repeated measures ANOVA showed significantly lower fault and fall times on the rotarod compared to sham mice (p = 0.0009, 0.0017, respectively, Figure 9B). The interaction between time and injury was not significant but was significant for time alone (p < 0.0001) showing that injured animals did not learn at a different rate than sham animals. At 4–5 days post injury, injured mice did not show a significant decreased preference for the displaced object than sham mice (p = 0.2345, Figure 9C) in the hippocampus dependent behavioral task, SOR. Additionally, the CFC task administered 7–8 days post injury also failed to elicit significant behavioral difference between injured and sham mice (p = 0.2182, Figure 9D). In all, mCCI produced early motor behavioral deficits.


A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice.

Chen Y, Mao H, Yang KH, Abel T, Meaney DF - Front Neurol (2014)

Mild controlled cortical impact leads to a transient behavioral impairment. A behavioral testing paradigm to examine both cortical and hippocampal function after impact is shown in (A). Rotarod (RR) training occurred the day before injury; RR was given on days 1–3 post injury. Spatial object recognition (SOR) was implemented on days 4 (training) and 5 (test day). Contextual fear conditioning (CFC) was given on days 7 (training) and 8 (test). The animals were perfused on day 8 after CFC. The rotarod results (B) indicate injured animals faulted at lower speeds with significantly lower fault and fall latency times as determine by a repeated measures ANOVA (p = 0.0009 and 0.0017, respectively). In neither the SOR (C) nor the CFC (D) (p = 0.2345, p = 0.2182, respectively) did injured mice show significant level of altered behavior. Sample size n = 17 sham, n = 19 injured. Data are expressed as media ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061598&req=5

Figure 9: Mild controlled cortical impact leads to a transient behavioral impairment. A behavioral testing paradigm to examine both cortical and hippocampal function after impact is shown in (A). Rotarod (RR) training occurred the day before injury; RR was given on days 1–3 post injury. Spatial object recognition (SOR) was implemented on days 4 (training) and 5 (test day). Contextual fear conditioning (CFC) was given on days 7 (training) and 8 (test). The animals were perfused on day 8 after CFC. The rotarod results (B) indicate injured animals faulted at lower speeds with significantly lower fault and fall latency times as determine by a repeated measures ANOVA (p = 0.0009 and 0.0017, respectively). In neither the SOR (C) nor the CFC (D) (p = 0.2345, p = 0.2182, respectively) did injured mice show significant level of altered behavior. Sample size n = 17 sham, n = 19 injured. Data are expressed as media ± SEM.
Mentions: In all, mCCI produced very mild early behavioral deficits (Figure 9A). Injured mice showed vestibulomotor impairment after injury, as evident through the rotarod testing results. In repeated measures ANOVA showed significantly lower fault and fall times on the rotarod compared to sham mice (p = 0.0009, 0.0017, respectively, Figure 9B). The interaction between time and injury was not significant but was significant for time alone (p < 0.0001) showing that injured animals did not learn at a different rate than sham animals. At 4–5 days post injury, injured mice did not show a significant decreased preference for the displaced object than sham mice (p = 0.2345, Figure 9C) in the hippocampus dependent behavioral task, SOR. Additionally, the CFC task administered 7–8 days post injury also failed to elicit significant behavioral difference between injured and sham mice (p = 0.2182, Figure 9D). In all, mCCI produced early motor behavioral deficits.

Bottom Line: Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury.Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively.Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Pennsylvania , Philadelphia, PA , USA.

ABSTRACT
For the past 25 years, controlled cortical impact (CCI) has been a useful tool in traumatic brain injury (TBI) research, creating injury patterns that includes primary contusion, neuronal loss, and traumatic axonal damage. However, when CCI was first developed, very little was known on the underlying biomechanics of mild TBI. This paper uses information generated from recent computational models of mild TBI in humans to alter CCI and better reflect the biomechanical conditions of mild TBI. Using a finite element model of CCI in the mouse, we adjusted three primary features of CCI: the speed of the impact to achieve strain rates within the range associated with mild TBI, the shape, and material of the impounder to minimize strain concentrations in the brain, and the impact depth to control the peak deformation that occurred in the cortex and hippocampus. For these modified cortical impact conditions, we observed peak strains and strain rates throughout the brain were significantly reduced and consistent with estimated strains and strain rates observed in human mild TBI. We saw breakdown of the blood-brain barrier but no primary hemorrhage. Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury. Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively. Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

No MeSH data available.


Related in: MedlinePlus