Evidence for vascular microbleeds in brains following repeated mild traumatic brain injury

Abstract

Mild traumatic brain injury (mTBI) is produced by the rapid movement of the brain within the skull. It is believed that each mTBI leaves the brain in a vulnerable state to subsequent injuries (repeated‐mTBI; r‐mTBI), and can precipitate more serious neurological conditions. However, a mechanism responsible for this vulnerable state is currently lacking, and the mTBI process itself remains poorly understood. The current experiments used an Awake Closed Head Injury (ACHI) model we have recently developed to study r‐mTBI. For each ACHI procedure (n = 8 per animal) a neurological assessment was performed to assess basic levels of consciousness, balance, and sensory perception. Our data demonstrate that administering the ACHI protocol 8 times produces robust, but non‐cumulative neurological deficits. One day following mTBI, rats were perfusion fixed, vibratome sliced (50 μm), and processed for immunohistochemistry. Confocal and light microscopic imaging revealed that r‐mTBI is accompanied by diffuse microbleeds in cortical and subcortical regions that ranged in size from 20 to 100 μm. These microbleeds were characterized by the presence of red blood cells and the blood protein, fibrinogen, in the surrounding perivascular space. The parenchyma around these microbleeds was positive for reactive and phagocytic microglia. In addition, the brains of animals following r‐mTBI were unique in that they also contained ‘rod’ type microglia, similar to those normally observed in Alzeheimer‐like dementias. These observations indicate that repeated concussions produce ruptures in small blood vessels in the brain and these likely contribute to both immediate and long‐term cognitive deficits.Support or Funding InformationCIHR, NSERC