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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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Ultrastructural time course of cellular changes associated with quisqualic acid excitotoxicity in the motoneuron of the spinal cord: NMDA receptor-mediated excitotoxicity resembles necrosis, and cellular changes induced by laminectomy in the motoneuron of the spinal cord: apoptosis. Electron micrographs illustrate motoneuronal changes associated with the necrotic-like degenerative neuronal morphology induced by quisqualic acid ((c), (e), (g)). A normal motoneuron from the spinal cord is shown for comparison in (a). Selected motoneurons displaying the predominant morphological changes at the different times after quisqualic acid injection (1 h, 24 h, and 6 weeks) were arranged in a temporal sequence to show the progression of excitotoxic injury ((c), (e), (g)), apoptotic changes in the laminectomy group were shown at corresponding time points ((b), (d), (f)). Refer to Section 3 for a description of nuclear changes.
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fig8: Ultrastructural time course of cellular changes associated with quisqualic acid excitotoxicity in the motoneuron of the spinal cord: NMDA receptor-mediated excitotoxicity resembles necrosis, and cellular changes induced by laminectomy in the motoneuron of the spinal cord: apoptosis. Electron micrographs illustrate motoneuronal changes associated with the necrotic-like degenerative neuronal morphology induced by quisqualic acid ((c), (e), (g)). A normal motoneuron from the spinal cord is shown for comparison in (a). Selected motoneurons displaying the predominant morphological changes at the different times after quisqualic acid injection (1 h, 24 h, and 6 weeks) were arranged in a temporal sequence to show the progression of excitotoxic injury ((c), (e), (g)), apoptotic changes in the laminectomy group were shown at corresponding time points ((b), (d), (f)). Refer to Section 3 for a description of nuclear changes.

Mentions: Ultrastructural changes associated with neuronal apoptosis and necrosis in the spinal cord of normal, laminectomy, and quisqualic acid injected were shown in Figure 8. The definitive changes to distinguish apoptosis and necrosis classically occur within the nucleus. Comparing with a normal control neuron (Figure 8(a)), the size of a nucleus was essentially the same at 1 hour, 24 hours, and 6 weeks of laminectomy (Figures 8(b), 8(d) and 8(f)) and quisqualic acid injected spinal cord (Figures 8(c), 8(e), and 8(g)). There was a round nucleus at an early stage of the process towards spindle-shape at 1 hour of laminectomy (Figure 8(b)). Neurons in 1 hour of quisqualic acid injected spinal cord showed essentially the same size of a round nucleus as the normal control neuron (Figure 8(c)).


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

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

Ultrastructural time course of cellular changes associated with quisqualic acid excitotoxicity in the motoneuron of the spinal cord: NMDA receptor-mediated excitotoxicity resembles necrosis, and cellular changes induced by laminectomy in the motoneuron of the spinal cord: apoptosis. Electron micrographs illustrate motoneuronal changes associated with the necrotic-like degenerative neuronal morphology induced by quisqualic acid ((c), (e), (g)). A normal motoneuron from the spinal cord is shown for comparison in (a). Selected motoneurons displaying the predominant morphological changes at the different times after quisqualic acid injection (1 h, 24 h, and 6 weeks) were arranged in a temporal sequence to show the progression of excitotoxic injury ((c), (e), (g)), apoptotic changes in the laminectomy group were shown at corresponding time points ((b), (d), (f)). Refer to Section 3 for a description of nuclear changes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4309244&req=5

fig8: Ultrastructural time course of cellular changes associated with quisqualic acid excitotoxicity in the motoneuron of the spinal cord: NMDA receptor-mediated excitotoxicity resembles necrosis, and cellular changes induced by laminectomy in the motoneuron of the spinal cord: apoptosis. Electron micrographs illustrate motoneuronal changes associated with the necrotic-like degenerative neuronal morphology induced by quisqualic acid ((c), (e), (g)). A normal motoneuron from the spinal cord is shown for comparison in (a). Selected motoneurons displaying the predominant morphological changes at the different times after quisqualic acid injection (1 h, 24 h, and 6 weeks) were arranged in a temporal sequence to show the progression of excitotoxic injury ((c), (e), (g)), apoptotic changes in the laminectomy group were shown at corresponding time points ((b), (d), (f)). Refer to Section 3 for a description of nuclear changes.
Mentions: Ultrastructural changes associated with neuronal apoptosis and necrosis in the spinal cord of normal, laminectomy, and quisqualic acid injected were shown in Figure 8. The definitive changes to distinguish apoptosis and necrosis classically occur within the nucleus. Comparing with a normal control neuron (Figure 8(a)), the size of a nucleus was essentially the same at 1 hour, 24 hours, and 6 weeks of laminectomy (Figures 8(b), 8(d) and 8(f)) and quisqualic acid injected spinal cord (Figures 8(c), 8(e), and 8(g)). There was a round nucleus at an early stage of the process towards spindle-shape at 1 hour of laminectomy (Figure 8(b)). Neurons in 1 hour of quisqualic acid injected spinal cord showed essentially the same size of a round nucleus as the normal control neuron (Figure 8(c)).

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