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High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves.

Angstman NB, Kiessling MC, Frank HG, Schmitz C - Front Behav Neurosci (2015)

Bottom Line: Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods.Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions.Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroanatomy, Ludwig-Maximilians University of Munich Munich, Germany.

ABSTRACT
In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI.

No MeSH data available.


Related in: MedlinePlus

Behavioral loss-of-function of C. elegans worms following shock wave exposure. (A) Increased exposure to shock waves resulted in decreased mean speed of movement in all groups of worms exposed to at least 30 shock waves (p < 0.05). Represented as individual points, 97 positive-lying outliers were found within shock wave exposed groups of worms. Horizontal lines within the boxes represent median speeds, dots within the boxes average speeds, and box and whiskers were plotted using the Tukey method. The numbers below the boxes indicate the numbers of worms per group. (B) Worms exhibited dose-dependent response to shock wave application (ED50 = 44.6 shock waves) using the parameter “speed of movement” (calculated using the average speed of each individual worm). The dots represent average speed of the worms in each exposure groups. (C) Worms exhibited dose-dependent response to shock wave application (ED50 = 112.9 shock waves) using the parameter “relative number of worms paralyzed.” The dots represent the fraction of worms paralyzed in each exposure group. (E) Control worms showed a normal distribution of speed of movement. (E,F) Groups of worms exposed to more than five shock waves exhibited significant right-hand skew (p < 0.05). Probability density curves are shown for 50 (E) and 500 (F) shock waves, respectively.
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Figure 2: Behavioral loss-of-function of C. elegans worms following shock wave exposure. (A) Increased exposure to shock waves resulted in decreased mean speed of movement in all groups of worms exposed to at least 30 shock waves (p < 0.05). Represented as individual points, 97 positive-lying outliers were found within shock wave exposed groups of worms. Horizontal lines within the boxes represent median speeds, dots within the boxes average speeds, and box and whiskers were plotted using the Tukey method. The numbers below the boxes indicate the numbers of worms per group. (B) Worms exhibited dose-dependent response to shock wave application (ED50 = 44.6 shock waves) using the parameter “speed of movement” (calculated using the average speed of each individual worm). The dots represent average speed of the worms in each exposure groups. (C) Worms exhibited dose-dependent response to shock wave application (ED50 = 112.9 shock waves) using the parameter “relative number of worms paralyzed.” The dots represent the fraction of worms paralyzed in each exposure group. (E) Control worms showed a normal distribution of speed of movement. (E,F) Groups of worms exposed to more than five shock waves exhibited significant right-hand skew (p < 0.05). Probability density curves are shown for 50 (E) and 500 (F) shock waves, respectively.

Mentions: Using two behavioral endpoints, we were able to demonstrate, for the first time, a dose-dependent effect of shock wave exposure on C. elegans. Increased exposure to shock waves resulted in statistically significantly (p < 0.05) decreased mean speed of movement while simultaneously increasing the proportion of worms rendered paralyzed (Figure 2A; Videos S4, S5; see also Figures 4A–C). Both parameters exhibited sigmoidal dose-response relationship (Figures 2B,C), and the half-maximal effective doses (ED50) at EFD = 0.016 mJ/mm2 (measured at a distance of 5 mm to the applicator) and shock wave frequency of 5 Hz were calculated to be 44.6 and 112.9 shock waves for speed of movement and the proportion of worms rendered paralyzed, respectively (Figures 2B,C).


High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves.

Angstman NB, Kiessling MC, Frank HG, Schmitz C - Front Behav Neurosci (2015)

Behavioral loss-of-function of C. elegans worms following shock wave exposure. (A) Increased exposure to shock waves resulted in decreased mean speed of movement in all groups of worms exposed to at least 30 shock waves (p < 0.05). Represented as individual points, 97 positive-lying outliers were found within shock wave exposed groups of worms. Horizontal lines within the boxes represent median speeds, dots within the boxes average speeds, and box and whiskers were plotted using the Tukey method. The numbers below the boxes indicate the numbers of worms per group. (B) Worms exhibited dose-dependent response to shock wave application (ED50 = 44.6 shock waves) using the parameter “speed of movement” (calculated using the average speed of each individual worm). The dots represent average speed of the worms in each exposure groups. (C) Worms exhibited dose-dependent response to shock wave application (ED50 = 112.9 shock waves) using the parameter “relative number of worms paralyzed.” The dots represent the fraction of worms paralyzed in each exposure group. (E) Control worms showed a normal distribution of speed of movement. (E,F) Groups of worms exposed to more than five shock waves exhibited significant right-hand skew (p < 0.05). Probability density curves are shown for 50 (E) and 500 (F) shock waves, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4319468&req=5

Figure 2: Behavioral loss-of-function of C. elegans worms following shock wave exposure. (A) Increased exposure to shock waves resulted in decreased mean speed of movement in all groups of worms exposed to at least 30 shock waves (p < 0.05). Represented as individual points, 97 positive-lying outliers were found within shock wave exposed groups of worms. Horizontal lines within the boxes represent median speeds, dots within the boxes average speeds, and box and whiskers were plotted using the Tukey method. The numbers below the boxes indicate the numbers of worms per group. (B) Worms exhibited dose-dependent response to shock wave application (ED50 = 44.6 shock waves) using the parameter “speed of movement” (calculated using the average speed of each individual worm). The dots represent average speed of the worms in each exposure groups. (C) Worms exhibited dose-dependent response to shock wave application (ED50 = 112.9 shock waves) using the parameter “relative number of worms paralyzed.” The dots represent the fraction of worms paralyzed in each exposure group. (E) Control worms showed a normal distribution of speed of movement. (E,F) Groups of worms exposed to more than five shock waves exhibited significant right-hand skew (p < 0.05). Probability density curves are shown for 50 (E) and 500 (F) shock waves, respectively.
Mentions: Using two behavioral endpoints, we were able to demonstrate, for the first time, a dose-dependent effect of shock wave exposure on C. elegans. Increased exposure to shock waves resulted in statistically significantly (p < 0.05) decreased mean speed of movement while simultaneously increasing the proportion of worms rendered paralyzed (Figure 2A; Videos S4, S5; see also Figures 4A–C). Both parameters exhibited sigmoidal dose-response relationship (Figures 2B,C), and the half-maximal effective doses (ED50) at EFD = 0.016 mJ/mm2 (measured at a distance of 5 mm to the applicator) and shock wave frequency of 5 Hz were calculated to be 44.6 and 112.9 shock waves for speed of movement and the proportion of worms rendered paralyzed, respectively (Figures 2B,C).

Bottom Line: Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods.Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions.Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroanatomy, Ludwig-Maximilians University of Munich Munich, Germany.

ABSTRACT
In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI.

No MeSH data available.


Related in: MedlinePlus