Temporal and Spatial Effects of Blast Overpressure on Blood-Brain Barrier Permeability in Traumatic Brain Injury

Abstract

Blast-induced traumatic brain injury (bTBI) is a “signature wound” in soldiers during training and in combat and has also become a major cause of morbidity in civilians due to increased insurgency. This work examines the role of blood-brain barrier (BBB) disruption as a result of both primary biomechanical and secondary biochemical injury mechanisms in bTBI. Extravasation of sodium fluorescein (NaF) and Evans blue (EB) tracers were used to demonstrate that compromise of the BBB occurs immediately following shock loading, increases in intensity up to 4 hours and returns back to normal in 24 hours. This BBB compromise occurs in multiple regions of the brain in the anterior-posterior direction of the shock wave, with maximum extravasation seen in the frontal cortex. Compromise of the BBB is confirmed by (a) extravasation of tracers into the brain, (b) quantification of tight-junction proteins (TJPs) in the brain and the blood, and (c) tracking specific blood-borne molecules into the brain and brain-specific proteins into the blood. Taken together, this work demonstrates that the BBB compromise occurs as a part of initial biomechanical loading and is a function of increasing blast overpressures.

Altered levels of plasma neuron‐derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury

“…1). Occludin and claudin‐5 are the main protein components of the tight junction of the BBB, which increase in concentration in brain tissues and blood after blast injury of rodent brains (9). NDE levels of claudin‐5 were significantly higher and of occludin were only marginally higher after acute mTBI than for either controls or subjects sustaining chronic mTBIs (Fig.…”

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers

“…4 Despite the increase in occurrence and public awareness, our understanding of the effects of blast and the mechanisms behind subsequent injury are limited. 5,6 Blast overpressure (BOP) events are capable of injuring the brain by means of high-energy pressure waves that are rapidly emitted from the explosive, which propagate from the object and turn into shock waves upon interacting with a medium-in this case, being the military warfighter. 7 The clinical and pathological effects of blast exposure varies depending on the magnitude of the detonation, proximity to the blast, and the use of protective gear [7][8][9] and includes, but is not limited to, neuronal swelling, subdural hematomas, myelin deformation, inflammation, loss of consciousness, temporary disorientation, sleep disturbances, memory deficits, and tinnitus.…”

BBB pathophysiology independent delivery of siRNA in traumatic brain injury

“…One approach to overcome BBB in TBI involves systemic administration of therapeutics while the BBB is physically breached post-injury (14)(15)(16). However, physical breaching of BBB in TBI is highly heterogeneous and varies greatly among patients, depending on the extent of primary injury (17)(18)(19)(20). Moreover, BBB can self-repair within a few hours to days post-injury to restore its integrity (16)(17)(18)(19)(20).…”