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

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.

Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats

“…These results suggested that the increased coexpression and expression levels of AQP4 and Kir4.1 might be involved in the formation of medullospinal edema and the induction of pathological changes in medullospinal tissues, as part of secondary ASCI; the inhibitory effects of MP on medullospinal edema might be associated with its reduction of the coexpression and expression levels of AQP4 and Kir4.1. Recent study demonstrated that MP administration following SCI reduced AQP4 expression and exacerbates edema 24 . The Cabrera-Aldana's 24 study showed that SCI increased AQP4 expression in the spinal cord white matter and that MP diminished such increase to baseline levels.…”

Methoxytetrahydro‐2H‐pyran‐2‐yl)methyl benzoate inhibits spinal cord injury in the rat model via PPAR‐γ/PI3K/p‐Akt activation

“…Spinal cord injury (SCI) is among the serious nervous system disorders characterized by complete or partial damage to motor function resulting in movement loss . Efforts are being continuously made to develop better treatment strategies for SCI . Each year around 20 to 40 people suffer from SCI in every one lakh people globally .…”

“…Each year around 20 to 40 people suffer from SCI in every one lakh people globally . The common causes responsible for SCI include sports injuries, fall from long distances and traffic accidents . The traffic accidents account for around 45% SCI cases in United States, fall from high altitudes for 17% and sports injuries for 12% .…”

“…The common causes responsible for SCI include sports injuries, fall from long distances and traffic accidents . The traffic accidents account for around 45% SCI cases in United States, fall from high altitudes for 17% and sports injuries for 12% . The SCI is caused generally in 18 to 80 years of age group but most commonly working people are affected leading to economic loss .…”

Resveratrol treatment of spinal cord injury in rat model

“…However, the use of MP is highly controversial owing to non-reproducibility of its beneficial effects as well as unwanted side effects (Evaniew et al, 2016;Liu et al, 2017;Shroff & Gupta, 2015). The American Association of Neurological Surgeons in their guidelines no longer recommend MP usage for the management of acute SCI (Cabrera-Aldana et al, 2017). In view of this, drug for SCI is, presently, an important research study for clinicians and scientists.…”