Methylprednisolone Administration Following Spinal Cord Injury Reduces Aquaporin 4 Expression and Exacerbates Edema.

Eibar Ernesto Cabrera-Aldana,Ruth Rincon-Heredia,Luis B Tovar-Y-Romo,Cristina Aranda,Angelina Martínez-Cruz,Alejandro Reyes-Sánchez,Gabriel Guizar-Sahagún,Fernando Ruelas

doi:10.1155/2017/4792932

Eibar Ernesto Cabrera-Aldana, Ruth Rincon-Heredia + Show 6 more

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https://doi.org/10.1155/2017/4792932

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Abstract

Spinal cord injury (SCI) is an incapacitating condition that affects motor, sensory, and autonomic functions. Since 1990, the only treatment administered in the acute phase of SCI has been methylprednisolone (MP), a synthetic corticosteroid that has anti-inflammatory effects; however, its efficacy remains controversial. Although MP has been thought to help in the resolution of edema, there are no scientific grounds to support this assertion. Aquaporin 4 (AQP4), the most abundant component of water channels in the CNS, participates in the formation and elimination of edema, but it is not clear whether the modulation of AQP4 expression by MP plays any role in the physiopathology of SCI. We studied the functional expression of AQP4 modulated by MP following SCI in an experimental model in rats along with the associated changes in the permeability of the blood-spinal cord barrier. We analyzed these effects in male and female rats and found that SCI increased AQP4 expression in the spinal cord white matter and that MP diminished such increase to baseline levels. Moreover, MP increased the extravasation of plasma components after SCI and enhanced tissue swelling and edema. Our results lend scientific support to the increasing motion to avoid MP treatment after SCI.

Highlights

Traumatic injury of the spinal cord generates a lesion that causes severe neurological alterations that afflict thousands of individuals every year, the exact number of affected people is difficult to assess, especially in low-middle income countries where records are not completely available [1]
More than 30 years ago, MP was considered to reduce lipid peroxidation triggered as secondary damage following Spinal cord injury (SCI) [4] and its use is largely justified on the National Acute Spinal Cord Injury Studies trial II (NASCIS II) [5, 6], in which the major finding was that a subgroup of patients treated with 30 mg/kg bolus at hospital admission followed by 5.4 mg/kg/h for the 23 h starting before 8 h of contusion showed a slight improvement in light touch and pinprick sensation and a very subtle motor improvement
At 24 h following contusion, the macroscopic lesion observed in the spinal cord was appreciably similar in the animals administered with MP in comparison with injured animals that received a corresponding volume of control vehicle (Figure 1)

Summary

Introduction

Traumatic injury of the spinal cord generates a lesion that causes severe neurological alterations that afflict thousands of individuals every year, the exact number of affected people is difficult to assess, especially in low-middle income countries where records are not completely available [1]. More than 30 years ago, MP was considered to reduce lipid peroxidation triggered as secondary damage following SCI [4] and its use is largely justified on the National Acute Spinal Cord Injury Studies trial II (NASCIS II) [5, 6], in which the major finding was that a subgroup of patients treated with 30 mg/kg bolus at hospital admission followed by 5.4 mg/kg/h for the 23 h starting before 8 h of contusion showed a slight improvement in light touch and pinprick sensation and a very subtle motor improvement. Administration of MP following SCI continues to be a common practice [8,9,10,11] notwithstanding that it is no longer recommended in the guidelines for the management of acute SCI of the American Association of Neurological surgeons [2]

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