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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 increases compensatory sprouting after SCI.(a) Diagram of BDA injections in the sensorimotor cortex. The position of SCI at C4 level is also indicated. (b) Representative pictures of sagittal spinal cord sections at C4 level of CTR-inj (left) and FLX treated (right) rats. Stars indicate lesion cavity. Arrows indicate traced sprouting CST fibers. Scale bar: 50 μm. (c) Quantification of sprouting fibers in the ventral grey matter at 0.5, 1.5, 2.5, 3.5, 4.5 mm from the lesion center, normalized on total counts at medulla oblongata level (100%). FLX rats showed more sprouting fibers at 1.5 and 4.5 mm caudal to the lesion than CTR-inj. Error bars represent SEM. Asterisks indicate statistical significance.
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f3: Fluoxetine increases compensatory sprouting after SCI.(a) Diagram of BDA injections in the sensorimotor cortex. The position of SCI at C4 level is also indicated. (b) Representative pictures of sagittal spinal cord sections at C4 level of CTR-inj (left) and FLX treated (right) rats. Stars indicate lesion cavity. Arrows indicate traced sprouting CST fibers. Scale bar: 50 μm. (c) Quantification of sprouting fibers in the ventral grey matter at 0.5, 1.5, 2.5, 3.5, 4.5 mm from the lesion center, normalized on total counts at medulla oblongata level (100%). FLX rats showed more sprouting fibers at 1.5 and 4.5 mm caudal to the lesion than CTR-inj. Error bars represent SEM. Asterisks indicate statistical significance.

Mentions: In order to investigate possible mechanisms underlying the beneficial effects elicited by fluoxetine, we analyzed sprouting of intact corticospinal fibers (CSTs). After completing the behavioral assessment, we bilaterally injected FLX and CTR-inj rats with the neuronal tracer biotinylated dextran amine (BDA) in the forepaw representation area of the sensorimotor cortex; then, we quantified the number of fibers at increasing distances from the lesion site (Fig 3a). We performed the anatomical analysis in the same animals that were tested in the Montoya staircase task. While no sprouting was observed at any distance in the CTR group, we found that FLX treatment was able to markedly increase sprouting level of CSTs (Two Way ANOVA, p < 0.01, Fig. 3c).


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 increases compensatory sprouting after SCI.(a) Diagram of BDA injections in the sensorimotor cortex. The position of SCI at C4 level is also indicated. (b) Representative pictures of sagittal spinal cord sections at C4 level of CTR-inj (left) and FLX treated (right) rats. Stars indicate lesion cavity. Arrows indicate traced sprouting CST fibers. Scale bar: 50 μm. (c) Quantification of sprouting fibers in the ventral grey matter at 0.5, 1.5, 2.5, 3.5, 4.5 mm from the lesion center, normalized on total counts at medulla oblongata level (100%). FLX rats showed more sprouting fibers at 1.5 and 4.5 mm caudal to the lesion than CTR-inj. Error bars represent SEM. Asterisks indicate statistical significance.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Fluoxetine increases compensatory sprouting after SCI.(a) Diagram of BDA injections in the sensorimotor cortex. The position of SCI at C4 level is also indicated. (b) Representative pictures of sagittal spinal cord sections at C4 level of CTR-inj (left) and FLX treated (right) rats. Stars indicate lesion cavity. Arrows indicate traced sprouting CST fibers. Scale bar: 50 μm. (c) Quantification of sprouting fibers in the ventral grey matter at 0.5, 1.5, 2.5, 3.5, 4.5 mm from the lesion center, normalized on total counts at medulla oblongata level (100%). FLX rats showed more sprouting fibers at 1.5 and 4.5 mm caudal to the lesion than CTR-inj. Error bars represent SEM. Asterisks indicate statistical significance.
Mentions: In order to investigate possible mechanisms underlying the beneficial effects elicited by fluoxetine, we analyzed sprouting of intact corticospinal fibers (CSTs). After completing the behavioral assessment, we bilaterally injected FLX and CTR-inj rats with the neuronal tracer biotinylated dextran amine (BDA) in the forepaw representation area of the sensorimotor cortex; then, we quantified the number of fibers at increasing distances from the lesion site (Fig 3a). We performed the anatomical analysis in the same animals that were tested in the Montoya staircase task. While no sprouting was observed at any distance in the CTR group, we found that FLX treatment was able to markedly increase sprouting level of CSTs (Two Way ANOVA, p < 0.01, Fig. 3c).

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