The science of concussion and chronic traumatic encephalopathy (CTE) is still emerging. Here are some findings from the literature.
Christopher Giza at the University of California, Los Angeles, has published on the neurometabolic cascade of concussion. Following concussion, cerebral pathophysiology includes abrupt neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, altered cerebral blood flow, and impaired axonal function (1).
His work from an animal model has focused on activated N-methyl-D-aspartate receptor (NMDA) changes after traumatic brain injury (TBI) (2).
Following activated NMDA receptors, excess intracellular calcium may be sequestered in the mitochondria, resulting in impaired oxidative metabolism and, ultimately, energy failure (3).
After an initial period of hyperglycolysis, cerebral glucose use is diminished by 24 hours post-injury and remains low for five to 10 days in experimental animals, and is demonstrated by PET scanning in humans that may last two to four weeks post-TBI...
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The science of concussion and chronic traumatic encephalopathy (CTE) is still emerging. Here are some findings from the literature.
Christopher Giza at the University of California, Los Angeles, has published on the neurometabolic cascade of concussion. Following concussion, cerebral pathophysiology includes abrupt neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, altered cerebral blood flow, and impaired axonal function (1).
His work from an animal model has focused on activated N-methyl-D-aspartate receptor (NMDA) changes after traumatic brain injury (TBI) (2).
Following activated NMDA receptors, excess intracellular calcium may be sequestered in the mitochondria, resulting in impaired oxidative metabolism and, ultimately, energy failure (3).
After an initial period of hyperglycolysis, cerebral glucose use is diminished by 24 hours post-injury and remains low for five to 10 days in experimental animals, and is demonstrated by PET scanning in humans that may last two to four weeks post-TBI (4).
Accelerated glycolysis leads to increased lactate production. The impairment of mitochondrial function can lead to reduced ATP production and lactate production concurrent with a decrease in lactate metabolism, resulting in lactate accumulation. Increased levels of lactate after TBI may leave neurons more vulnerable to a secondary ischemic injury (1).
Reduction in magnesium, diffuse axonal injury, delayed cell death, persistent calcium accumulation, and neurotransmitter alteration (NMDA, adrenergic and cholinergic system post-concussion receptor) have been described (1).
The results of repeated concussion (CTE) have been found in the brains of a number of former football players who have suffered from TBI and taken their lives. It has recently been described upon autopsy in the press and Scientific American. Football is not alone, as rugby, soccer, and hockey players; boxers; wrestlers; soldiers; and victims of physical abuse have also been reported (5).
Examination of these victims’ brains leaves a signature somewhat analogous to Alzheimer’s but distinct: microscopic clumps of tau proteins. Patients with CTE don’t have the extensive plaques characteristic of Alzheimer’s, and their tau clumps tend to be patchier. McKee and her colleagues published a review in the Journal of Neuropathology and Experimental Neurology (6).
The treatment of mild post-concussion syndrome is in its infancy, with early recognition, psychological testing, and taking the victim out of the game and resting the brain. The only FDA-approved OTC, acetaminophen (paracetamol), has been studied for mild concussion headaches. A potent N-type calcium channel blocker (SNX-111), NMDA receptor blockers (MK-801 and HU-211), and a synthetic cannabinoid with pharmacological profile of an NMDA receptor antagonist have been reported in experimental models (1).
The increased awareness of post-concussion syndrome and now CTE is a perfect storm for both NFL-funded, NIH-sponsored, military, big pharma, and biotech research.
References:
1. Giza CC, Hovda DA. The Neurometabolic Cascade of Concussion. J Athl Train. 2001 Sep;36(3):228-235. Abstract
2. Giza CC, Maria NS, Hovda DA. N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. J Neurotrauma. 2006 Jun;23(6):950-61. Abstract
3. Verweij BH, Muizelaar JP, Vinas FC, Peterson PL, Xiong Y, Lee CP. Mitochondrial dysfunction after experimental and human brain injury and its possible reversal with a selective N-type calcium channel antagonist (SNX-111). Neurol Res. 1997 Jun;19(3):334-9. Abstract
4. Bergsneider M, Hovda DA, Lee SM, Kelly DF, McArthur DL, Vespa PM, Lee JH, Huang SC, Martin NA, Phelps ME, Becker DP. Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J Neurotrauma. 2000 May;17(5):389-401. Abstract
5. Wilyard C. Brain damage on the playing field. Scientific American. Feb 24, 2011.
6. McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C, Morin P, Lee HS, Kubilus CA, Daneshvar DH, Wulff M, Budson AE. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol. 2010 Sep;69(9):918-29. Abstract
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