Selective vulnerability of the cerebral vasculature to blast injury in a rat model of mild traumatic brain injury.

Miguel A Gama Sosa,Gregory A Elder,Eric Maudlin-Jeronimo,Bridget Wicinski,Alejandro J Paulino,Pierce L Janssen,Pamela C Anazodo,Patrick R Hof,Stephen T Ahlers,Richard M Mccarron,Frank J Yuk,Aaron A Hall,Rita De Gasperi,Paul E Pricop,Dara L Dickstein,Mikulas Chavko,Michael C Shaughness

doi:10.1186/2051-5960-2-67

Abstract

BackgroundBlast-related traumatic brain injury (TBI) is a common cause of injury in the military operations in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. The aim of the present study was to examine whether blast exposure affects the cerebral vasculature in a rodent model. We analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24 hours or between 6 and 10 months after exposure. Blast-induced cerebral vascular pathology was examined by a combination of light microscopy, immunohistochemistry, and electron microscopy.ResultsWe describe a selective vascular pathology that is present acutely at 24 hours after injury. The vascular pathology is found at the margins of focal shear-related injuries that, as we previously showed, typically follow the patterns of penetrating cortical vessels. However, changes in the microvasculature extend beyond the margins of such lesions. Electron microscopy revealed that microvascular pathology is found in regions of the brain with an otherwise normal neuropil. This initial injury leads to chronic changes in the microvasculature that are still evident many months after the initial blast exposure.ConclusionsThese studies suggest that vascular pathology may be a central mechanism in the induction of chronic blast-related injury.

Highlights

Blast exposure is a rare cause of traumatic brain injury (TBI) in civilian life [1]
There have been concerns that blast injury, like forms of non-blast TBI, may be associated with the later development of progressive neurodegenerative disorders such as Alzheimer’s disease or chronic traumatic encephalopathy (CTE) [5] and multiple cases of CTE have been described in veterans from Iraq and Afghanistan [6,7]
In a previous study of rats subjected to 74.5 kPa blast exposures, we described a type of shear injury in the brain that has not been described in non-blast TBI (nbTBI) models and appears to be unique to blast-associated brain injury [12]

Summary

Introduction

Blast exposure is a rare cause of traumatic brain injury (TBI) in civilian life [1]. Single or multiple blast-related mTBIs have been associated with chronic neurological and psychiatric symptoms [3]. There have been concerns that blast injury, like forms of non-blast TBI (nbTBI), may be associated with the later development of progressive neurodegenerative disorders such as Alzheimer’s disease or chronic traumatic encephalopathy (CTE) [5] and multiple cases of CTE have been described in veterans from Iraq and Afghanistan [6,7]. Blast-related traumatic brain injury (TBI) is a common cause of injury in the military operations in Iraq and Afghanistan. We analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Blast-induced cerebral vascular pathology was examined by a combination of light microscopy, immunohistochemistry, and electron microscopy

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