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Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury.

Scali M, Begenisic T, Mainardi M, Milanese M, Bonifacino T, Bonanno G, Sale A, Maffei L - Sci Rep (2013)

Bottom Line: We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms.The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance.Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience CNR, Pisa, Italy.

ABSTRACT
Spinal cord injury (SCI) is a severe condition leading to enduring motor deficits. When lesions are incomplete, promoting spinal cord plasticity might be a useful strategy to elicit functional recovery. Here we investigated whether long-term fluoxetine administration in the drinking water, a treatment recently demonstrated to optimize brain plasticity in several pathological conditions, promotes motor recovery in rats that received a C4 dorsal funiculus crush. We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms. The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance. Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies.

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Fluoxetine induces recovery of motor functions after SCI.(a, b) Staircase. After SCI, all rats lost grasping ability. Starting from the 2nd week, FLX rats began to retrieve significantly more pellets and showed a greater accuracy than CTR-inj. (c, d) Horizontal ladder. After SCI, the number of footslips was significantly increased in all groups. Starting from the 4th week, FLX rats showed a better performance than CTR-inj. The performance of CTR-sham rats did not change throughout the testing period. Box-whisker plot: the horizontal lines in the box denote the 25th, 50th (median), and 75th percentile values; the small square inside the box represents the mean; error bars denote the 5th and 95th percentile values. X represents max and min values. Curves: error bars represent SEM. Symbols indicate statistical difference.
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f1: Fluoxetine induces recovery of motor functions after SCI.(a, b) Staircase. After SCI, all rats lost grasping ability. Starting from the 2nd week, FLX rats began to retrieve significantly more pellets and showed a greater accuracy than CTR-inj. (c, d) Horizontal ladder. After SCI, the number of footslips was significantly increased in all groups. Starting from the 4th week, FLX rats showed a better performance than CTR-inj. The performance of CTR-sham rats did not change throughout the testing period. Box-whisker plot: the horizontal lines in the box denote the 25th, 50th (median), and 75th percentile values; the small square inside the box represents the mean; error bars denote the 5th and 95th percentile values. X represents max and min values. Curves: error bars represent SEM. Symbols indicate statistical difference.

Mentions: We started to analyze FLX and CTR rat behavior in the Montoya staircase task13, which allows assessing forelimb skilled reaching ability (Fig. 1a, b). We recorded the mean total number of eaten pellets and the performance accuracy (i.e. the ratio between the number of eaten pellets and the sum of eaten and unsuccessfully displaced pellets). Before injury, baseline performance did not differ between FLX and CTR animals (eaten pellets: Mann-Whitney Rank Sum Test, p = 0.420; accuracy: Mann-Whitney Rank Sum Test, p = 0.713). One week after SCI all injured rats were unable to grasp and eat pellets, thus confirming the severity of the lesion received. By the second week post-surgery, FLX animals began to significantly improve their performance compared to CTR-inj rats (Two-Way RM ANOVA, post-hoc Holm-Sidak method, p < 0.05 for both eaten pellets and accuracy). The improvement resulted in a performance of about 60% of pre-injury baseline in the sixth week after SCI, when the CTR-inj group displayed only a 30% of pre-injury performance. The performance of CTR-sham rats did not change throughout the testing period (eaten pellets: One-Way RM ANOVA, p = 0.095; accuracy: One-Way RM ANOVA, p = 0.881).


Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury.

Scali M, Begenisic T, Mainardi M, Milanese M, Bonifacino T, Bonanno G, Sale A, Maffei L - Sci Rep (2013)

Fluoxetine induces recovery of motor functions after SCI.(a, b) Staircase. After SCI, all rats lost grasping ability. Starting from the 2nd week, FLX rats began to retrieve significantly more pellets and showed a greater accuracy than CTR-inj. (c, d) Horizontal ladder. After SCI, the number of footslips was significantly increased in all groups. Starting from the 4th week, FLX rats showed a better performance than CTR-inj. The performance of CTR-sham rats did not change throughout the testing period. Box-whisker plot: the horizontal lines in the box denote the 25th, 50th (median), and 75th percentile values; the small square inside the box represents the mean; error bars denote the 5th and 95th percentile values. X represents max and min values. Curves: error bars represent SEM. Symbols indicate statistical difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3713566&req=5

f1: Fluoxetine induces recovery of motor functions after SCI.(a, b) Staircase. After SCI, all rats lost grasping ability. Starting from the 2nd week, FLX rats began to retrieve significantly more pellets and showed a greater accuracy than CTR-inj. (c, d) Horizontal ladder. After SCI, the number of footslips was significantly increased in all groups. Starting from the 4th week, FLX rats showed a better performance than CTR-inj. The performance of CTR-sham rats did not change throughout the testing period. Box-whisker plot: the horizontal lines in the box denote the 25th, 50th (median), and 75th percentile values; the small square inside the box represents the mean; error bars denote the 5th and 95th percentile values. X represents max and min values. Curves: error bars represent SEM. Symbols indicate statistical difference.
Mentions: We started to analyze FLX and CTR rat behavior in the Montoya staircase task13, which allows assessing forelimb skilled reaching ability (Fig. 1a, b). We recorded the mean total number of eaten pellets and the performance accuracy (i.e. the ratio between the number of eaten pellets and the sum of eaten and unsuccessfully displaced pellets). Before injury, baseline performance did not differ between FLX and CTR animals (eaten pellets: Mann-Whitney Rank Sum Test, p = 0.420; accuracy: Mann-Whitney Rank Sum Test, p = 0.713). One week after SCI all injured rats were unable to grasp and eat pellets, thus confirming the severity of the lesion received. By the second week post-surgery, FLX animals began to significantly improve their performance compared to CTR-inj rats (Two-Way RM ANOVA, post-hoc Holm-Sidak method, p < 0.05 for both eaten pellets and accuracy). The improvement resulted in a performance of about 60% of pre-injury baseline in the sixth week after SCI, when the CTR-inj group displayed only a 30% of pre-injury performance. The performance of CTR-sham rats did not change throughout the testing period (eaten pellets: One-Way RM ANOVA, p = 0.095; accuracy: One-Way RM ANOVA, p = 0.881).

Bottom Line: We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms.The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance.Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience CNR, Pisa, Italy.

ABSTRACT
Spinal cord injury (SCI) is a severe condition leading to enduring motor deficits. When lesions are incomplete, promoting spinal cord plasticity might be a useful strategy to elicit functional recovery. Here we investigated whether long-term fluoxetine administration in the drinking water, a treatment recently demonstrated to optimize brain plasticity in several pathological conditions, promotes motor recovery in rats that received a C4 dorsal funiculus crush. We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms. The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance. Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies.

Show MeSH
Related in: MedlinePlus