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The roads to mitochondrial dysfunction in a rat model of posttraumatic syringomyelia.

Hu Z, Tu J - Biomed Res Int (2015)

Bottom Line: If so, whether it causes neuronal mitochondrial dysfunction and depletion, and subsequent energy metabolism impairment results in cell starvation of energy and even cell death, contributing to the enlargement of the cavity.We found an 86 ± 11% reduction of local blood flow at C8 where a cyst formed at 6 weeks after syrinx induction procedure (P < 0.05), and no difference in blood flow rate between the laminectomy and intact controls.Our findings demonstrate that an excitotoxic injury induces local ischemia in the spinal cord and results in neuronal mitochondrial depletion, and profound ATP loss, contributing to syrinx enlargement.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

ABSTRACT
The pathophysiology of posttraumatic syringomyelia is incompletely understood. We examined whether local ischemia occurs after spinal cord injury. If so, whether it causes neuronal mitochondrial dysfunction and depletion, and subsequent energy metabolism impairment results in cell starvation of energy and even cell death, contributing to the enlargement of the cavity. Local blood flow was measured in a rat model of posttraumatic syringomyelia that had received injections of quisqualic acid and kaolin. We found an 86 ± 11% reduction of local blood flow at C8 where a cyst formed at 6 weeks after syrinx induction procedure (P < 0.05), and no difference in blood flow rate between the laminectomy and intact controls. Electron microscopy confirmed irreversible neuronal mitochondrion depletion surrounding the cyst, but recoverable mitochondrial loses in laminectomy rats. Profound energy loss quantified in the spinal cord of syrinx animals, and less ATP and ADP decline observed in laminectomy rats. Our findings demonstrate that an excitotoxic injury induces local ischemia in the spinal cord and results in neuronal mitochondrial depletion, and profound ATP loss, contributing to syrinx enlargement. Ischemia did not occur following laminectomy induced trauma in which mitochondrial loss and decline in ATP were reversible. This confirms excitotoxic injury contributing to the pathology of posttraumatic syringomyelia.

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Related in: MedlinePlus

Quantification of ischemic motoneuronal change, ghost motoneuron, and spongy vacuolization in the spinal cord of intact control, laminectomy, and syrinx groups at 1 h, 24 h, and 6 weeks after injury. Data expressed as mean ± SE from 4–63 separate H and E stained sections. (a) Ischemic motoneuronal change. *P < 0.03, versus intact control at the same time point. Spinal cord injury, regardless of laminectomy or syrinx procedure, induced ischemic motoneuronal change. Such ischemic cell change was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. The initial ischemic motoneuronal change occurred in the spinal cord of syrinx rats could be recovered within 24 h following injury but it reoccurred at 6-week time point. (b) Ghost motoneurons were observed as motoneurons without nucleus. *P < 0.015, versus intact control at the same time point. †P < 0.0001, versus other groups at all 3 time points. Spinal cord injury, regardless of laminectomy or syrinx procedure, increased the percentage of ghost motoneuron. A high percentage of ghost motoneuron was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. There was no significant difference in the percentage of ghost motoneuron between laminectomy groups. At 6-week-time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point. (c) The percentage of vacuoles in a coronal spinal cord section. *P < 0.05, versus intact control at the same time point. †P < 0.02, versus laminectomy at 1 h and syrinx at 1 h. ‡P < 0.01, versus other groups at all 3 time points except syrinx at 24 h. Spinal cord injury, regardless laminectomy or syrinx procedure, increased the percentage of vacuoles in the spinal cord. A higher percentage of vacuoles was observed at 6 h in the laminectomy group than at 1 h in both laminectomy and syrinx animals. At 6-week time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point except syrinx at 24 h.
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fig7: Quantification of ischemic motoneuronal change, ghost motoneuron, and spongy vacuolization in the spinal cord of intact control, laminectomy, and syrinx groups at 1 h, 24 h, and 6 weeks after injury. Data expressed as mean ± SE from 4–63 separate H and E stained sections. (a) Ischemic motoneuronal change. *P < 0.03, versus intact control at the same time point. Spinal cord injury, regardless of laminectomy or syrinx procedure, induced ischemic motoneuronal change. Such ischemic cell change was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. The initial ischemic motoneuronal change occurred in the spinal cord of syrinx rats could be recovered within 24 h following injury but it reoccurred at 6-week time point. (b) Ghost motoneurons were observed as motoneurons without nucleus. *P < 0.015, versus intact control at the same time point. †P < 0.0001, versus other groups at all 3 time points. Spinal cord injury, regardless of laminectomy or syrinx procedure, increased the percentage of ghost motoneuron. A high percentage of ghost motoneuron was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. There was no significant difference in the percentage of ghost motoneuron between laminectomy groups. At 6-week-time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point. (c) The percentage of vacuoles in a coronal spinal cord section. *P < 0.05, versus intact control at the same time point. †P < 0.02, versus laminectomy at 1 h and syrinx at 1 h. ‡P < 0.01, versus other groups at all 3 time points except syrinx at 24 h. Spinal cord injury, regardless laminectomy or syrinx procedure, increased the percentage of vacuoles in the spinal cord. A higher percentage of vacuoles was observed at 6 h in the laminectomy group than at 1 h in both laminectomy and syrinx animals. At 6-week time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point except syrinx at 24 h.

Mentions: The number of motoneurons with the degenerative morphologies was summarized in Figure 7. There were 2% motoneurons with ischemic cell changes per spinal cord cross section in intact control (Figure 7(a)). In the laminectomy group, this percentage increased by 2.6- and 3.3-fold at 1 hour and 24 hours, respectively (P < 0.03), and partially recovered by 24% 6 weeks later. In syrinx group, the percentage of ischemic cell changes increased by 4.6- and 6.9-fold at 1 hour and 24 hours, respectively (P < 0.02), and sustained at 1 hour level 6 weeks later. In addition, there were 1% motoneurons being identified as ghost neuron per spinal cord cross section in the intact controls (Figure 7(b)). Such a percentage increased significantly by 10.4- and 18.6-fold at 1 hour and 24 hours, respectively (P < 0.02) before a partial recovery from injury to 1 hour level 6 weeks later. In contrast, the percentage of ghost neuron linearly increased with time by 14.7-, 36.7-, and 65.3-fold at 1 hour, 24 hours, and 6 weeks in syrinx group.


The roads to mitochondrial dysfunction in a rat model of posttraumatic syringomyelia.

Hu Z, Tu J - Biomed Res Int (2015)

Quantification of ischemic motoneuronal change, ghost motoneuron, and spongy vacuolization in the spinal cord of intact control, laminectomy, and syrinx groups at 1 h, 24 h, and 6 weeks after injury. Data expressed as mean ± SE from 4–63 separate H and E stained sections. (a) Ischemic motoneuronal change. *P < 0.03, versus intact control at the same time point. Spinal cord injury, regardless of laminectomy or syrinx procedure, induced ischemic motoneuronal change. Such ischemic cell change was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. The initial ischemic motoneuronal change occurred in the spinal cord of syrinx rats could be recovered within 24 h following injury but it reoccurred at 6-week time point. (b) Ghost motoneurons were observed as motoneurons without nucleus. *P < 0.015, versus intact control at the same time point. †P < 0.0001, versus other groups at all 3 time points. Spinal cord injury, regardless of laminectomy or syrinx procedure, increased the percentage of ghost motoneuron. A high percentage of ghost motoneuron was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. There was no significant difference in the percentage of ghost motoneuron between laminectomy groups. At 6-week-time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point. (c) The percentage of vacuoles in a coronal spinal cord section. *P < 0.05, versus intact control at the same time point. †P < 0.02, versus laminectomy at 1 h and syrinx at 1 h. ‡P < 0.01, versus other groups at all 3 time points except syrinx at 24 h. Spinal cord injury, regardless laminectomy or syrinx procedure, increased the percentage of vacuoles in the spinal cord. A higher percentage of vacuoles was observed at 6 h in the laminectomy group than at 1 h in both laminectomy and syrinx animals. At 6-week time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point except syrinx at 24 h.
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Related In: Results  -  Collection

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fig7: Quantification of ischemic motoneuronal change, ghost motoneuron, and spongy vacuolization in the spinal cord of intact control, laminectomy, and syrinx groups at 1 h, 24 h, and 6 weeks after injury. Data expressed as mean ± SE from 4–63 separate H and E stained sections. (a) Ischemic motoneuronal change. *P < 0.03, versus intact control at the same time point. Spinal cord injury, regardless of laminectomy or syrinx procedure, induced ischemic motoneuronal change. Such ischemic cell change was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. The initial ischemic motoneuronal change occurred in the spinal cord of syrinx rats could be recovered within 24 h following injury but it reoccurred at 6-week time point. (b) Ghost motoneurons were observed as motoneurons without nucleus. *P < 0.015, versus intact control at the same time point. †P < 0.0001, versus other groups at all 3 time points. Spinal cord injury, regardless of laminectomy or syrinx procedure, increased the percentage of ghost motoneuron. A high percentage of ghost motoneuron was reversible in the spinal cord of laminectomy animals but not in syrinx rats during 6 weeks follow-up period. There was no significant difference in the percentage of ghost motoneuron between laminectomy groups. At 6-week-time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point. (c) The percentage of vacuoles in a coronal spinal cord section. *P < 0.05, versus intact control at the same time point. †P < 0.02, versus laminectomy at 1 h and syrinx at 1 h. ‡P < 0.01, versus other groups at all 3 time points except syrinx at 24 h. Spinal cord injury, regardless laminectomy or syrinx procedure, increased the percentage of vacuoles in the spinal cord. A higher percentage of vacuoles was observed at 6 h in the laminectomy group than at 1 h in both laminectomy and syrinx animals. At 6-week time point, the percentage of ghost motoneuron was greater in syrinx than any other groups at every time point except syrinx at 24 h.
Mentions: The number of motoneurons with the degenerative morphologies was summarized in Figure 7. There were 2% motoneurons with ischemic cell changes per spinal cord cross section in intact control (Figure 7(a)). In the laminectomy group, this percentage increased by 2.6- and 3.3-fold at 1 hour and 24 hours, respectively (P < 0.03), and partially recovered by 24% 6 weeks later. In syrinx group, the percentage of ischemic cell changes increased by 4.6- and 6.9-fold at 1 hour and 24 hours, respectively (P < 0.02), and sustained at 1 hour level 6 weeks later. In addition, there were 1% motoneurons being identified as ghost neuron per spinal cord cross section in the intact controls (Figure 7(b)). Such a percentage increased significantly by 10.4- and 18.6-fold at 1 hour and 24 hours, respectively (P < 0.02) before a partial recovery from injury to 1 hour level 6 weeks later. In contrast, the percentage of ghost neuron linearly increased with time by 14.7-, 36.7-, and 65.3-fold at 1 hour, 24 hours, and 6 weeks in syrinx group.

Bottom Line: If so, whether it causes neuronal mitochondrial dysfunction and depletion, and subsequent energy metabolism impairment results in cell starvation of energy and even cell death, contributing to the enlargement of the cavity.We found an 86 ± 11% reduction of local blood flow at C8 where a cyst formed at 6 weeks after syrinx induction procedure (P < 0.05), and no difference in blood flow rate between the laminectomy and intact controls.Our findings demonstrate that an excitotoxic injury induces local ischemia in the spinal cord and results in neuronal mitochondrial depletion, and profound ATP loss, contributing to syrinx enlargement.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

ABSTRACT
The pathophysiology of posttraumatic syringomyelia is incompletely understood. We examined whether local ischemia occurs after spinal cord injury. If so, whether it causes neuronal mitochondrial dysfunction and depletion, and subsequent energy metabolism impairment results in cell starvation of energy and even cell death, contributing to the enlargement of the cavity. Local blood flow was measured in a rat model of posttraumatic syringomyelia that had received injections of quisqualic acid and kaolin. We found an 86 ± 11% reduction of local blood flow at C8 where a cyst formed at 6 weeks after syrinx induction procedure (P < 0.05), and no difference in blood flow rate between the laminectomy and intact controls. Electron microscopy confirmed irreversible neuronal mitochondrion depletion surrounding the cyst, but recoverable mitochondrial loses in laminectomy rats. Profound energy loss quantified in the spinal cord of syrinx animals, and less ATP and ADP decline observed in laminectomy rats. Our findings demonstrate that an excitotoxic injury induces local ischemia in the spinal cord and results in neuronal mitochondrial depletion, and profound ATP loss, contributing to syrinx enlargement. Ischemia did not occur following laminectomy induced trauma in which mitochondrial loss and decline in ATP were reversible. This confirms excitotoxic injury contributing to the pathology of posttraumatic syringomyelia.

Show MeSH
Related in: MedlinePlus