Thursday, February 1, 2018

Concussions not necessary for CTE, according to impressive mouse model

Fig. 5 (Tagge, Fisher, Minaeva et al., 2018). Unilateral, closed-head impact injury induces focal blood–brain barrier disruption, serum albumin extravasation, astrocytosis, myeloid inflammatory cell infiltration, and TREM2+ microglial activation in cerebral cortex ipsilateral and subjacent to impact.

Repeated concussions in contact sports — mild traumatic brain injuries (TBIs) due to head impact — have been linked to the development of chronic traumatic encephalopathy (CTE) in human athletes. This unique neurodegenerative disorder has been characterized by abnormal accumulations of hyperphosphorylated tau protein after repeated TBIs.

Now, a tour de force by the MADLab of Dr. Lee Goldstein has convincingly demonstrated that head impact itself, but not necessarily the cognitive and behavioral sequelae associated with “clinical” concussions, can cause CTE-like pathology in a mouse model (Tagge, Fisher, Minaeva, et al., 2018).

Not one, but two figures have panels extending from A to HH.

Supplementary Fig. 3. (Tagge, Fisher, Minaeva et al., 2018). Experimental exposure to a single closed-head impact injury induces traumatic microvascular injury, astrocytosis, microgliosis and progressive phosphorylated tauopathy) in cerebral cortex ipsilateral and subjacent to the impact contact zone.

The authors developed a detailed model of the cellular and molecular events that occur after closed-head impact injury.

Fig. 8 (Tagge, Fisher, Minaeva et al., 2018). Model of traumatic microvascular injury, blood–brain barrier disruption, microglial activation, perivascular neuroinflammation, myelinated axonopathy, and phosphorylated tauopathy after closed-head impact injury.

Another strong aspect of the paper is the inclusion of neuropathology from the post-mortem brains of eight young male athletes. Four died from impact-related closed head injuries, while the other four served as controls. A critical element here is that one of the controls died from oxycodone overdose and another died by suicide — factors that have been neglected in previous studies. I'd like to take a closer look at these brains in a subsequent post.

But it's possible to show post-mortem CTE pathology without having suffered a single blow to the head, so there's still a lot to learn.


Tagge CA, Fisher AM, Minaeva OV, Gaudreau-Balderrama A, Moncaster JA, Zhang XL, Wojnarowicz MW, Casey N, Lu H, Kokiko-Cochran ON, Saman S, Ericsson M, Onos KD, Veksler R, Senatorov VV Jr, Kondo A, Zhou XZ, Miry O, Vose LR, Gopaul KR, Upreti C, Nowinski CJ, Cantu RC, Alvarez VE, Hildebrandt AM, Franz ES, Konrad J, Hamilton JA, Hua N, Tripodis Y, Anderson AT, Howell GR, Kaufer D, Hall GF, Lu KP, Ransohoff RM, Cleveland RO, Kowall NW, Stein TD, Lamb BT, Huber BR, Moss WC, Friedman A, Stanton PK, McKee AC, Goldstein LE. (2018). Concussion, microvascular injury,and early tauopathy in young athletes after impact head injury and an impact concussion mouse model. Brain 141: 422-458.

Further Reading

Blast Wave Injury and Chronic Traumatic Encephalopathy: What's the Connection?

Goldstein, L., Fisher, A., Tagge, C., Zhang, X., Velisek, L., Sullivan, J., Upreti, C., Kracht, J., Ericsson, M., Wojnarowicz, M., Goletiani, C., Maglakelidze, G., Casey, N., Moncaster, J., Minaeva, O., Moir, R., Nowinski, C., Stern, R., Cantu, R., Geiling, J., Blusztajn, J., Wolozin, B., Ikezu, T., Stein, T., Budson, A., Kowall, N., Chargin, D., Sharon, A., Saman, S., Hall, G., Moss, W., Cleveland, R., Tanzi, R., Stanton, P., & McKee, A. (2012). Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model. Science Translational Medicine, 4 (134), 134-134 DOI: 10.1126/scitranslmed.3003716/