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The Neuroprotective Effect of Tetramethylpyrazine Against Contusive Spinal Cord Injury by Activating PGC-1α in Rats.

Hu J, Lang Y, Cao Y, Zhang T, Lu H - Neurochem. Res. (2015)

Bottom Line: TMP treatment markedly increased PGC-1α expression, neuronal survival and BBB locomotor scores, while also reducing neural apoptosis.These results demonstrate that TMP is neuroprotective against contusive SCI, with the inhibition of neural apoptosis and increase of neuronal survival.The sustained expression of PGC-1α may partially contribute to the TMP-mediated neuroprotective effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China.

ABSTRACT
Tetramethylpyrazine (TMP) has been suggested to have neuroprotective effects against spinal cord injury (SCI); however, few studies have examined these effects and the corresponding mechanism. Therefore, the present study aimed to investigate the neuroprotective effect and underlying mechanism of TMP against contusive SCI. Adult male Sprague-Dawley rats were randomly divided into Sham, normal saline (NS) and TMP groups. Each group was divided into subgroups according to the time of sacrifice: 1, 3, 7, 14, 21 and 28 days post-injury. Laminectomy was performed in all groups, followed by contusive SCI establishment in the TMP and NS groups. TMP (80 mg/kg) was injected thereafter daily from 3 to 7 days post-injury in the TMP group, which was replaced by equal volume of normal saline in the NS group. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale was measured at different time points post-injury to appraise locomotor functional recovery. Quantitative real-time PCR and immunofluorescence were used to assess the spatio-temporal expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), while western blot was adopted to detect the effect of TMP on PGC-1α. Neural apoptotic changes and neuronal survival were evaluated using the TUNEL method and Nissl staining, respectively. TMP treatment markedly increased PGC-1α expression, neuronal survival and BBB locomotor scores, while also reducing neural apoptosis. These results demonstrate that TMP is neuroprotective against contusive SCI, with the inhibition of neural apoptosis and increase of neuronal survival. The sustained expression of PGC-1α may partially contribute to the TMP-mediated neuroprotective effect.

No MeSH data available.


Related in: MedlinePlus

Immunofluorescence staining of the spatial expression of PGC-1α. The first row of images (a–c) demonstrates that PGC-1α is mainly expressed in the grey matter of the spinal cord in normal rats, and has a main co-localization with the neurons in the ventral horn. The β-III tubulin antibody was used to detect neurons. White arrow heads indicate the representative expression location of PGC-1α, and white arrows are representative of its co-localization with the neuronal marker. Double-staining at higher magnification in the second and third rows of images (d–i) clearly shows predominant overlap between neurons and PGC-1α in spinal cord tissues both pre- and post-contusive spinal cord injury. Scale bar 20 μm
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Fig3: Immunofluorescence staining of the spatial expression of PGC-1α. The first row of images (a–c) demonstrates that PGC-1α is mainly expressed in the grey matter of the spinal cord in normal rats, and has a main co-localization with the neurons in the ventral horn. The β-III tubulin antibody was used to detect neurons. White arrow heads indicate the representative expression location of PGC-1α, and white arrows are representative of its co-localization with the neuronal marker. Double-staining at higher magnification in the second and third rows of images (d–i) clearly shows predominant overlap between neurons and PGC-1α in spinal cord tissues both pre- and post-contusive spinal cord injury. Scale bar 20 μm

Mentions: Overall, PGC-1α expression significantly decreased after contusive SCI, followed by a gradual increase, in correlation with the spontaneous repair, until it reached a plateau. Specifically, relative to the normal control, the PGC-1α expression at 1 day post-injury decreased by about 80 %. From 7 days post-injury, an obvious increase occurred, but the expression level was still less than 60 % of the normal control at the end of our observation (Fig. 2). PGC-1α expression was mainly located in the grey matter of normal spinal cord. Besides, there was a high degree of overlap between neurons and PGC-1α, particularly in the ventral horn, while double staining devoid of neuronal marker could also be found. After injury, the main co-localization of neurons and PGC-1α could still be discovered despite the morphological abnormalities of the preserved neurons (Fig. 3). It is highly possible that PGC-1α plays a role of neuronal origin in protecting spinal cord homeostasis.Fig. 2


The Neuroprotective Effect of Tetramethylpyrazine Against Contusive Spinal Cord Injury by Activating PGC-1α in Rats.

Hu J, Lang Y, Cao Y, Zhang T, Lu H - Neurochem. Res. (2015)

Immunofluorescence staining of the spatial expression of PGC-1α. The first row of images (a–c) demonstrates that PGC-1α is mainly expressed in the grey matter of the spinal cord in normal rats, and has a main co-localization with the neurons in the ventral horn. The β-III tubulin antibody was used to detect neurons. White arrow heads indicate the representative expression location of PGC-1α, and white arrows are representative of its co-localization with the neuronal marker. Double-staining at higher magnification in the second and third rows of images (d–i) clearly shows predominant overlap between neurons and PGC-1α in spinal cord tissues both pre- and post-contusive spinal cord injury. Scale bar 20 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493940&req=5

Fig3: Immunofluorescence staining of the spatial expression of PGC-1α. The first row of images (a–c) demonstrates that PGC-1α is mainly expressed in the grey matter of the spinal cord in normal rats, and has a main co-localization with the neurons in the ventral horn. The β-III tubulin antibody was used to detect neurons. White arrow heads indicate the representative expression location of PGC-1α, and white arrows are representative of its co-localization with the neuronal marker. Double-staining at higher magnification in the second and third rows of images (d–i) clearly shows predominant overlap between neurons and PGC-1α in spinal cord tissues both pre- and post-contusive spinal cord injury. Scale bar 20 μm
Mentions: Overall, PGC-1α expression significantly decreased after contusive SCI, followed by a gradual increase, in correlation with the spontaneous repair, until it reached a plateau. Specifically, relative to the normal control, the PGC-1α expression at 1 day post-injury decreased by about 80 %. From 7 days post-injury, an obvious increase occurred, but the expression level was still less than 60 % of the normal control at the end of our observation (Fig. 2). PGC-1α expression was mainly located in the grey matter of normal spinal cord. Besides, there was a high degree of overlap between neurons and PGC-1α, particularly in the ventral horn, while double staining devoid of neuronal marker could also be found. After injury, the main co-localization of neurons and PGC-1α could still be discovered despite the morphological abnormalities of the preserved neurons (Fig. 3). It is highly possible that PGC-1α plays a role of neuronal origin in protecting spinal cord homeostasis.Fig. 2

Bottom Line: TMP treatment markedly increased PGC-1α expression, neuronal survival and BBB locomotor scores, while also reducing neural apoptosis.These results demonstrate that TMP is neuroprotective against contusive SCI, with the inhibition of neural apoptosis and increase of neuronal survival.The sustained expression of PGC-1α may partially contribute to the TMP-mediated neuroprotective effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China.

ABSTRACT
Tetramethylpyrazine (TMP) has been suggested to have neuroprotective effects against spinal cord injury (SCI); however, few studies have examined these effects and the corresponding mechanism. Therefore, the present study aimed to investigate the neuroprotective effect and underlying mechanism of TMP against contusive SCI. Adult male Sprague-Dawley rats were randomly divided into Sham, normal saline (NS) and TMP groups. Each group was divided into subgroups according to the time of sacrifice: 1, 3, 7, 14, 21 and 28 days post-injury. Laminectomy was performed in all groups, followed by contusive SCI establishment in the TMP and NS groups. TMP (80 mg/kg) was injected thereafter daily from 3 to 7 days post-injury in the TMP group, which was replaced by equal volume of normal saline in the NS group. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale was measured at different time points post-injury to appraise locomotor functional recovery. Quantitative real-time PCR and immunofluorescence were used to assess the spatio-temporal expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), while western blot was adopted to detect the effect of TMP on PGC-1α. Neural apoptotic changes and neuronal survival were evaluated using the TUNEL method and Nissl staining, respectively. TMP treatment markedly increased PGC-1α expression, neuronal survival and BBB locomotor scores, while also reducing neural apoptosis. These results demonstrate that TMP is neuroprotective against contusive SCI, with the inhibition of neural apoptosis and increase of neuronal survival. The sustained expression of PGC-1α may partially contribute to the TMP-mediated neuroprotective effect.

No MeSH data available.


Related in: MedlinePlus