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Aquaporins in spinal cord injury: the janus face of aquaporin 4.

ABSTRACT: Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates glial fibrillary acidic protein (GFAP)-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study observed changes in human SCI. AQP4-negative astrocytes are likely generated during the process of SCI-induced replacement of lost astrocytes, but their origin and role in SCI remains to be investigated. We found that AQP4-overexpression is likely triggered by hypoxia. Our transcriptional profiling of injured rat cords suggests that elevated AQP4-mediated water influx accompanies increased uptake of chloride and potassium ions which represents a protective astrocytic reaction to hypoxia. However, unbalanced water intake also results in astrocytic swelling that can contribute to motor impairment, but likely only in milder injuries. In severe rat SCI, a low abundance of AQP4-overexpressing astrocytes was found during the motor recovery phase. Our results suggest that severe rat contusion SCI is a better model to analyze AQP4 functions after SCI. We found that AQP4 increases in the chronic post-injury phase are associated with the development of pain-like behavior in SCI rats, while possible mechanisms underlying pain development may involve astrocytic swelling-induced glutamate release. In contrast, the formation and size of fluid-filled cavities occurring later after SCI does not appear to be affected by the extent of increased AQP4 levels. Therefore, the effect of therapeutic interventions targeting AQP4 will depend not only on the time interval after SCI or animal models, but also on the balance between protective role of increased AQP4 in hypoxia and deleterious effects of ongoing astrocytic swelling.

SUBMITTER: Nesic O

PROVIDER: S-EPMC2885549 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Aquaporins in spinal cord injury: the janus face of aquaporin 4.

Nesic O O Guest J D JD Zivadinovic D D Narayana P A PA Herrera J J JJ Grill R J RJ Mokkapati V U L VU Gelman B B BB Lee J J

Neuroscience 20100128 4

Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates glial fibrillary acidic protein (GFAP)-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study obser ...[more]

PMID: 20109536

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Project description:OBJECTIVE: High-energy impact to the head, neck, and shoulder can result in cervical spine as well as brachial plexus injuries. Because cervical spine injuries are more common, this tends to be the initial focus for management. We present a case in which the initial magnetic resonance imaging (MRI) was somewhat misleading and a detailed neurological exam lead to the correct diagnosis. CLINICAL PRESENTATION: A 19-year-old man presented to the hospital following a shoulder injury during football practice. The patient immediately complained of significant pain in his neck, shoulder, and right arm and the inability to move his right arm. He was stabilized in the field for a presumed cervical-spine injury and transported to the emergency department. INTERVENTION: Initial radiographic assessment (C-spine CT, right shoulder x-ray) showed no bony abnormality. MRI of the cervical-spine showed T2 signal change and cord swelling thought to be consistent with a cord contusion. With adequate pain control, a detailed neurological examination was possible and was consistent with an upper brachial plexus avulsion injury that was confirmed by CT myelogram. The patient failed to make significant neurological recovery and he underwent spinal accessory nerve grafting to the suprascapular nerve to restore shoulder abduction and external rotation, while the phrenic nerve was grafted to the musculocutaneous nerve to restore elbow flexion. CONCLUSION: Cervical spinal-cord injuries and brachial plexus injuries can occur by the same high energy mechanisms and can occur simultaneously. As in this case, MRI findings can be misleading and a detailed physical examination is the key to diagnosis. However, this can be difficult in polytrauma patients with upper extremity injuries, head injuries or concomitant spinal-cord injury. Finally, prompt diagnosis and early surgical renerveration have been associated with better long-term recovery with certain types of injury.

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Aquaporins in spinal cord injury: the janus face of aquaporin 4.

Publications

Aquaporins in spinal cord injury: the janus face of aquaporin 4.

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