Repairing Neural Damage in Concussion and Mild Traumatic Brain Injury: (mTBI): The role of targeted dietary supplements

James Meschino DC, MS, ROHP

Conventional medical treatment of concussion and mild traumatic brain injury (mTBI) is limited.  The majority of concussion patientsare known to recover within days-to-weeks, however, approximately 10% of patients develop persistent signs and symptoms of post-concussion syndrome (PCS). Currently, there are no scientifically established treatments for concussion or PCS, and thus rest and cognitive rehabilitation are traditionally applied, with varying degrees of success. In recent years a number of preclinical and clinical studies have shown that administration of targeted dietary supplements can repair neural damage resulting from mTBIand speed recovery in patients with documented signs and symptoms of concussions and PC, respectively. This review highlights the physiological mechanisms by which targeted dietary supplements have been shown to reverse neural damage in preclinical studies involving mTBI, and improve signs and symptoms in patients with documented concussions and PCS from available preliminary clinical studies and case reports.

Nerual Damage in Mild Traumatic Brain Injury (mTBI)
Concussion and mild traumatic brain injury are the result of rapid deceleration of the brain with the skull that imparts shearing or torsional forces to neural tissue followed by metabolic and mechanical changes. (1) The pathophysiological changes induced by mTBIhave been reported to include the following:

• Disruption of the neurofilaments and microtubules: Initially, there is evidence disruption of the neurofilaments and microtubules that provide a framework for axonal transport. This compromises anterograde and retrograde transport of molecular proteins to and from the cell body (somata).
• Proteolysis:In mTBIaxonal transport can also be affected by delayed, progressive injury secondary to proteolysis of nerve cell proteins.
• Neural Membrane Disruption and Inflammation:Evidence suggests that disruption and inflammation of the neural membrane leads to ionic shifts and an increase in intracellular glutamate and calcium. High intracellular glutamate is known to be toxic to brain cells. Some cells may ultimately undergo caspase-mediated apoptosis as a result of these cellular changes. Inflammatory cascades also contribute significantly to additional brain cell dysfunction. Neuroinflammatory cascades have been shown to play a significant role in the pathogenesis of neural disease following concussion and possibly repetitive sub-concussive injury.
• Altered Glucose Metabolism:mTBI has been shown to induce changes to neuronal glucose metabolism by inducinghyperglycolysis and oxidative dysfunction with increased production of reactive oxygen species (ROS).
• Mitochondrial injury:mTBI has been shown to reduce adenosine triphosphate (ATP) generation and produce an increase in reactive oxygen species. Decreased ATP production is thought to hinder nerve cell repair ability.
• Reduced Cerebral Blood Flow: mTBI is also shown to produce a calcium-induced vasoconstriction in affected areas of the brain. (1,2)

Taken together, there is well documented evidence of axonal injury inmTBI, which is sometimes visible on MRI because of eventual cell death. Diffuse axonal injury is considered instrumental in causing cognitive sequalae, such as memory difficulties and concentration problems. The changes involve initial depolarization of neuronal membranes and the release of excitatory amino acids, particularly glutamate, which produces fluxes of calcium and potassium ions across neural and vascular tissue resulting in a hypermetabolic glycolytic state as the neurons attempt to restore equilibrium. There follows a calcium ion-induced vasoconstriction that reduces cerebral blood flow and glucose delivery with a resultant metabolic depression (brain energy demand not adequately met, which may last for days). These changes appear to render neural tissue more susceptible to further injury. (1)

Supplementation in Concussion Management
Preclinical studies have shown that many of the pathophysiological changes induced by mTBI can be reversed to a greater or lesser extent through the administration of specific, targeted dietary supplements. In addition, several human clinical trials and single case studies have shown that specific dietary supplements have reduced signs and symptoms in concussion and post concussion syndrome in preliminary investigations. As repairing neural damage caused by mTBI is a high priority in these cases, a review of the therapeutic effects of supplement administration in mTBI is worthy of consideration. This reviewhighlights the therapeutic effects that targeted dietary supplements have demonstrated in mTBI, based on preclinical studies and preliminary clinical investigations.

1. Willer B, Leddy JL. Management of concussion and post-concussion syndrome. Current treatment options in Neurology. 2006, 8:415-426
2. Petraglia AL, Winkler EA, and Bailes JE. Stuck at the bench: Potential natural neuroprotective compounds for concussion.SurgNeurol Int. 2011; 2: 146. Published online 2011 October 12. doi:  4103/2152-7806.85987