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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

Parameters of mild CCI. The mild CCI (mCCI) uses a hemispherical silicone tip, actuated by a solenoid (A). A potentiometer records the displacement of the impactor, while the angle and height of the impactor are fully adjustable. A comparison of displaced tissue volume between mild CCI (2 mm impact depth, 0.43 m/s impact velocity) and traditional CCI (1 mm impact depth, 4–6 m/s impact velocity) is shown in (B). (C) Shows the range of impact speeds between tCCI (2.0–6.0 m/s) and the velocity range that would generate clinical TBI strain rates (17–104 s−1 for 0.1–0.6 m/s, respectively). The red line is the impactor speed used in this study (0.43 m/s for a strain rate of approximately 75 s−1). Brains perfused 8 days after a sham injury (D), mCCI with 2 mm impact depth (E), and tCCI with an impact depth and speed of 1 mm and 6.0 m/s, respectively (F).
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Figure 2: Parameters of mild CCI. The mild CCI (mCCI) uses a hemispherical silicone tip, actuated by a solenoid (A). A potentiometer records the displacement of the impactor, while the angle and height of the impactor are fully adjustable. A comparison of displaced tissue volume between mild CCI (2 mm impact depth, 0.43 m/s impact velocity) and traditional CCI (1 mm impact depth, 4–6 m/s impact velocity) is shown in (B). (C) Shows the range of impact speeds between tCCI (2.0–6.0 m/s) and the velocity range that would generate clinical TBI strain rates (17–104 s−1 for 0.1–0.6 m/s, respectively). The red line is the impactor speed used in this study (0.43 m/s for a strain rate of approximately 75 s−1). Brains perfused 8 days after a sham injury (D), mCCI with 2 mm impact depth (E), and tCCI with an impact depth and speed of 1 mm and 6.0 m/s, respectively (F).

Mentions: Using this as a guide, we constructed a modified cortical impact device on a mounting frame to minimize vibration during impact, and to align the indentor in the impact plane (Figure 2). A linear potentiometer (LP803-1, Omega, USA) measured the actuation of the solenoid and a custom Matlab (Mathworks, MA, USA) program controlled the solenoid and collected the potentiometer readings. The impactor was aligned 20° from vertical (measured with a digital angle meter), similar to other lateral CCI models. We also used a dwell time – defined as the duration over which the indentor is compressed into the brain – within the ranges (25–250 ms) for rodent CCI as cited in the literature (75). We could achieve higher impact speeds (4–6 m/s) if desired (Figure 2C), but chose to focus most of our efforts on the slower impact speed. At this lower impact speed, we saw no evidence of tissue necrosis 8 days after impact injury, unlike the extensive necrotic cavity that would appear after an impact using more commonly used impact speeds (4–6 m/s; Figure 2D).


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)

Parameters of mild CCI. The mild CCI (mCCI) uses a hemispherical silicone tip, actuated by a solenoid (A). A potentiometer records the displacement of the impactor, while the angle and height of the impactor are fully adjustable. A comparison of displaced tissue volume between mild CCI (2 mm impact depth, 0.43 m/s impact velocity) and traditional CCI (1 mm impact depth, 4–6 m/s impact velocity) is shown in (B). (C) Shows the range of impact speeds between tCCI (2.0–6.0 m/s) and the velocity range that would generate clinical TBI strain rates (17–104 s−1 for 0.1–0.6 m/s, respectively). The red line is the impactor speed used in this study (0.43 m/s for a strain rate of approximately 75 s−1). Brains perfused 8 days after a sham injury (D), mCCI with 2 mm impact depth (E), and tCCI with an impact depth and speed of 1 mm and 6.0 m/s, respectively (F).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Parameters of mild CCI. The mild CCI (mCCI) uses a hemispherical silicone tip, actuated by a solenoid (A). A potentiometer records the displacement of the impactor, while the angle and height of the impactor are fully adjustable. A comparison of displaced tissue volume between mild CCI (2 mm impact depth, 0.43 m/s impact velocity) and traditional CCI (1 mm impact depth, 4–6 m/s impact velocity) is shown in (B). (C) Shows the range of impact speeds between tCCI (2.0–6.0 m/s) and the velocity range that would generate clinical TBI strain rates (17–104 s−1 for 0.1–0.6 m/s, respectively). The red line is the impactor speed used in this study (0.43 m/s for a strain rate of approximately 75 s−1). Brains perfused 8 days after a sham injury (D), mCCI with 2 mm impact depth (E), and tCCI with an impact depth and speed of 1 mm and 6.0 m/s, respectively (F).
Mentions: Using this as a guide, we constructed a modified cortical impact device on a mounting frame to minimize vibration during impact, and to align the indentor in the impact plane (Figure 2). A linear potentiometer (LP803-1, Omega, USA) measured the actuation of the solenoid and a custom Matlab (Mathworks, MA, USA) program controlled the solenoid and collected the potentiometer readings. The impactor was aligned 20° from vertical (measured with a digital angle meter), similar to other lateral CCI models. We also used a dwell time – defined as the duration over which the indentor is compressed into the brain – within the ranges (25–250 ms) for rodent CCI as cited in the literature (75). We could achieve higher impact speeds (4–6 m/s) if desired (Figure 2C), but chose to focus most of our efforts on the slower impact speed. At this lower impact speed, we saw no evidence of tissue necrosis 8 days after impact injury, unlike the extensive necrotic cavity that would appear after an impact using more commonly used impact speeds (4–6 m/s; Figure 2D).

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