Magnesium Miracle? Exploring Its Role in Spinal Cord Injury

Introduction

Magnesium (Mg²⁺), despite being 12^th on the periodic table of elements, is one of the most prevalent and important ions in the human body. Yet its impact is often overlooked. Together let’s explore the profound impact of magnesium on inflammation and neurological outcomes in spinal cord injury (SCI) recovery. From animal models to clinical trials, we will delve into the research attempting to uncover the potential magnesium holds as a neuroprotective element for individuals with SCI.

Background

Magnesium has been of particular interest for neuro-recovery and management of different central nervous system conditions because it plays a part in over 300 different cellular processes, including maintaining optimal nerve transmission and communication, blood-brain-barrier integrity, and neuromuscular coordination. It has also been widely regarded for its diverse physiological role in maintaining homeostasis in the heart, brain, muscles, and bones.

One of its key roles in the central nervous system is to block a specific receptor type integral to neuron firing. So, when magnesium levels are low, dysregulation of this receptor can lead to toxic overstimulation of neurons. In the context of SCI, overstimulation of neurons may contribute to secondary injury, or further tissue damage, processes after the initial injury.

Magnesium in the brain is also important for blood-brain-barrier integrity. This barrier surrounds the brain and spinal cord and is important for protecting them against harmful substances in the outside environment. After SCI, the barrier integrity is impaired leading to introduction of molecules not typical to the brain and spinal cord environment, which can cause further tissue damage.

Magnesium & SCI

The reason magnesium is an important point of discussion in relation to SCI is that studies have reported magnesium decline during the acute stage. Furthermore, decline in magnesium is associated with higher levels of inflammatory molecules (known as cytokines) and worse neurological outcomes in individuals with SCI. Additionally, as mentioned previously, magnesium implicated BBB integrity breakdown may contribute to secondary injury in SCI individuals. Due to this, magnesium has been and continues to be researched as a potential therapeutic.

Magnesium as a Therapeutic

While there is good evidence of magnesium supplementation for other conditions, the role of magnesium for the SCI population is not quite as understood. In the management of neurocritical patients, magnesium improved antioxidant function, reduced inflammatory cytokine and toxic oxidative molecule production, and diminished cell death. Animal models have demonstrated increased tissue sparing and motor recovery with magnesium. Another animal study investigated the protective effect of magnesium sulfate (commonly known as Epsom salt) and measured functional score and immune system over activity biomarkers in rats with SCI. This study found that magnesium sulphate treatment improved early functional scores of the rats, decreased immune activity, and led to neuroprotection of the rat spinal cord.

In 2013, a clinical trial conducted by Acorda Therapeutics used a particular formulation with magnesium called AC-105. AC-105 is a drug that pairs magnesium with polyethylene glycol, which improves magnesium’s ability to act on the spinal cord. Unfortunately, the trial ended prematurely and no official conclusions about clinical use of AC-105 in SCI patients was made. SCI rat models studying AC-105 have shown positive results, including homeostasis of magnesium and reduction of neurotoxic glutamate levels. However, AC-105 administration in a SCI pig model showed no motor recovery. Clearly there is much work to be done surrounding the potential usage of magnesium as a tool for SCI recovery, especially in the clinical environment.

But despite some promising experimental studies, magnesium has not been proven clinically effective yet. While it is unlikely that targeting a single factor will be the cure for SCI, magnesium may still be a useful neuroprotective agent as part of a combination treatment regime that targets multiple components of the injury process.