Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury

Yu, Yonghao; Matsuyama, Yukihiro; Nakashima, Shojiro; Yanase, Makoto; Kiuchi, Kazutoshi; Ishiguro, Naoki

doi:10.1097/00001756-200409150-00021

Cited by 26 publications

(21 citation statements)

References 19 publications

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“…The results demonstrated that iNOS expression was upregulated after SCI and positively correlated to the apoptotic index. Nitric oxide (NO) is produced when nitric oxide synthase (NOS) catalyzes L-arginine to generate citrulline, and studies 22,23 have shown that overdose of NO produced by iNOS was found to induce cell apoptosis in the traumatic SCI models, so inhibition of iNOS may be an efficient therapy for secondary SCI. Our experimental results showed the percentage of iNOS-positive cells and apoptotic index of nerve cells in the EGb group was significantly lower than that in the NS group, which suggested that EGb 761 suppressed iNOS expression and then prevented nerve cell death.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats

Sun

Wang

et al. 2006

Spinal Cord

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Study design: An experimental animal model was used to assess spinal cord injury following lateral hemitransection at thoracic spinal cord level. Objective: To determine whether extract of Ginkgo biloba (EGb) could have a neuroprotective effect in spinal cord injury (SCI) in rats. Setting: Department of Biological Sciences and Biotechnology, Tsinghua University, China. Methods: A total of 72 adult rats were divided randomly into three groups: the EGb group, normal saline (NS) group, and sham operation group (sham group). After thoracic spinal cord hemitransection was performed at the level of the 9th thoracic vertebra (T9), rats in the EGb group were given 100 mg/kg EGb 761 daily, while rats in the NS group received NS. The rats in the sham group only underwent laminectomy without spinal cord hemitransection. At various time points after surgery, thoracic spinal cords were sampled and sliced for histochemistry, immunohistochemistry of inducible nitric oxide synthase (iNOS), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of apoptotic cells. Results: Myelin staining showed that the area of cavities was small and the demyelinated zones were limited at and around the injury site of the spinal cord in the EGb group, while the area of cavities was large and the demyelinated zones were serious in the NS group. Nissl staining showed that the ratio of bilateral ventral horn neurons (transection side/uninjured side) in the EGb group was higher than that in the NS group (Po0.05). The apoptotic index and the percentage of iNOS-positive cells were lower in the EGb group than in the NS group. Furthermore, the percentage of iNOS-positive cells positively correlated with the apoptotic index (r 2 ¼ 0.729, Po0.01) after SCI. Conclusion: This study demonstrated that EGb 761 could inhibit iNOS expression and have neuroprotective effect by preventing nerve cells from apoptosis after SCI in rats.

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Section: Discussionmentioning

confidence: 99%

Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats

Sun

Wang

et al. 2006

Spinal Cord

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“…Two results of the present study are difficult to reconcile, namely, that the MP group had the lowest oligodendrocyte AI and a relatively high TPC count and the other concerns the observed anti-inflammatory effect of GP. In general, it is considered that steroid therapy can enhance neurologic recovery after SCI augmenting behavior recovery and it is in fact the most widely used therapy in clinical conditions [2,32]. Nevertheless, exact mechanism of action is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…However, although a few studies have been conducted on the effects of steroid on neuronal and glial apoptosis, results are controversial. Yu et al [32] reported that early treatment with MP after SCI reduces inducible nitric oxide synthetase expression, and concluded that MP acts as a neuroprotector by inhibiting neuronal apoptosis. On the other hand, Li et al [18] concluded that MP treatment after SCI does not reduce the expression of caspase-3, a key enzyme of apoptosis, after rat spinal cord transection, and Diem et al [4] reported that steroid treatment has a negative effect on neuronal apoptosis in the autoimmune disease of the optic nerve.…”

Section: Discussionmentioning

confidence: 99%

Pregabalin as a neuroprotector after spinal cord injury in rats

Kim

Rhyu

et al. 2008

Eur Spine J

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The over-expression of excitotoxic neurotransmitter, such as glutamate, is an important mechanism of secondary injury after spinal cord injury. The authors examined the neuroprotective effect of pregabalin (GP) which is known as to reduce glutamate secretion, in a rat model of spinal cord injury. Thirty-two male SpragueDawley rats were randomly allocated to four groups; the control group (contusion injury only), the methylprednisolone treated group, the minocycline treated group and the GP treated group. Spinal cord injury was produced by contusion using the New York University impactor (25 gcm, at the 9th-10th thoracic). Functional evaluations were done using the inclined plane test and a motor rating scale. Anti-apoptotic and anti-inflammatory effects were evaluated by in situ nick-end labeling staining technique (TUNEL) and immunofluorescence staining of cord tissues obtained at 7 days post-injury. Pregabalin treated animals showed significantly better functional recovery, and antiapoptotic and anti-inflammatory effects. Mean numbers of TUNEL positive cells in the respective groups were 63.5 ± 7.4, 53.6 ± 4.0, 44.2 ± 3.9 and 36.5 ± 3.6. Double staining (TUNEL and anti-CC1) for oligodendrocyte apoptosis, was used to calculate oligodendrocyte apoptotic indexes (AI), using the following formula AI = (No. of doubly stained cells/No. of anti-CC1 positive cells) 9 100.Mean group AIs were 88.6, 46.7, 82.1 and 70.3%, respectively. Mean numbers of activated microglia (anti-OX-42 positive cells) in high power fields were 29.8 ± 3.9, 22.7 ± 4.1, 21.0 ± 3.9 and 17.8 ± 4.3, respectively. This experiment demonstrates that GP can act as a neuroprotector after SCI in rats, and its anti-apoptotic and anti-inflammatory effects are related to its neuroprotective effect. Further studies are needed to unveil the specific mechanism involved at the receptor level.

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“…Multiple animal studies have shown that high-dose methylprednisolone treatment of acute spinal cord injury results in a reduction in biochemical mediators of secondary neurological injury [1][2][3][4][5][6] and significantly improved neurological function. [7][8][9][10][11] Unfortunately, results in humans have been less sanguine.…”

Section: Introductionmentioning

confidence: 99%

Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and myeloperoxidase content in a pig model of acute spinal cord injury

Bernards

Akers

2006

Spinal Cord

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Objectives: To determine whether postinjury methylprednisolone could reduce the generation of known mediators of secondary neurological injury. Methods: Intrathecal microdialysis probes were used to sample cerebrospinal fluid (CSF) for measurement of PGE 2 , glutamate, and citrulline (a byproduct of nitric oxide generation), before and after spinal cord injury in anesthetized pigs. The spinal cord was removed at the end of the study for measurement of myeloperoxidase and methylprednisolone concentrations. Animals were randomly allocated to receive intravenous methylprednisolone (30 mg/kg bolus then 3.4 mg/kg/h), intrathecal methylprednisolone (5 mg bolus then 5 mg/h), or saline, beginning 30 min after the spinal cord was injured by using a modification of the Allen weight drop technique. Results: Spinal cord injury significantly increased the amount of glutamate, PGE 2 , myeloperoxidase, and citrulline, recovered from the CSF dialysates. However, neither intravenous nor intrathecal methylprednisolone administered after injury had any effect on the magnitude of the increase in any of the measured biochemicals. Intrathecal methylprednisolone administration produced a spinal cord methylprednisolone concentration that was eight times greater, and a plasma concentration that was 32 times less, than that achieved with intravenous administration. Conclusions: Contrary to earlier animal studies in which methylprednisolone was administered either before or immediately after spinal cord injury, we found no effect of intravenous or intrathecal methylprednisolone on any of the parameters measured when administered 30 min postinjury.

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Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury

Cited by 26 publications

References 19 publications

Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats

Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats

Pregabalin as a neuroprotector after spinal cord injury in rats

Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and myeloperoxidase content in a pig model of acute spinal cord injury

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