Opening of the Blood-Brain Barrier Tight Junction Due to Shock Wave Induced Bubble Collapse: A Molecular Dynamics Simulation Study

Abstract

Passage of a shock wave across living organisms may produce bubbles in the blood vessels and capillaries. It was suggested that collapse of these bubbles imposed by an impinging shock wave can be responsible for the damage or even destruction of the blood-brain barrier. To check this possibility, we performed molecular dynamics computer simulations on systems that contained a model of tight junction from the blood-brain barrier. In our model, we represent the tight junction by two pairs of interacting proteins, claudin-15. Some of the simulations were done in the absence of a nanobubble, some in its presence. Our simulations show that when no bubble is present in the system, no damage to tight junction is observed when the shock wave propagates across it. In the presence of a nanobubble, even when the impulse of the shock wave is relatively low, the implosion of the bubble causes serious damage to our model tight junction.

Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated Perineuronal Net of the Brain

“…2. The mechanism of bubble collapse agrees well with many existing simulation studies 23–25, 30, 31, 55, 56, 60 . It can be inferred from Fig.…”

“…Until now, most experimental studies mimicking blast-like scenarios are observed via optical microscopy, which are limited by the device resolution being 1 μm or higher 2, 8, 19–21 . Of these studies, only a handful of studies have been reported on how different micro-scale brain components, such as cell membranes (lipid bilayers) 2, 22–29 , ion channel 30 , and blood-brain barrier 31, 32 , respond to impact caused by cavitation bubble collapse. While these studies explored various components of the brain when subjected to a shock-wave and cavitation collapse, little is known about the role of a shock-wave on the morphological evolution of a brain’s extracellular matrix (ECM) 19 .…”

“…To investigate these issues, we used reactive molecular dynamics simulation (reaxFF potential) 49, 50 to model the events occurring at the nanometer scale and sub-nanosecond time frame. While conventional molecular dynamics simulation can capture events like bubble ripening 51–53 and collapse 23, 24, 30, 31, 54–58 in homogenous fluids, the use of reactive molecular dynamics is essential to the assessment of PNN damage because of PNN’s heterogeneous morphology. The simulation results demonstrate the possible shock-induced damage mechanisms of HA due to bubble collapse.…”

Nanotherapy for Early Dementia: Targeting Senile Dementia

“…Lastly, a completely separate and additional advantage of such LCM/ND lipid nanoemulsion(s), as a component of this combination therapeutic, stems from the characteristic lipid-coated microbubble subpopulation (D'Arrigo 2011) existing in this nanoemulsion type. Specifically, such preformed (lipidstabilized) microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment Alonso et al 2010;Alonso et al 2011;Aslund et al 2017;Bing et al 2014;D'Arrigo 2015;Delalande et al 2013;Goliaei et al 2015;Kotopoulis et al 2013;Kotopoulis et al 2014;Lammers et al 2015;Marquet et al 2011;Meairs 2015;Meng et al 2017;Miller and O'Callaghan 2017), or sonoporation (Aubry et al 2016;Bouakaz et al 2016;Burgess and Hynynen 2016;Castle and Feinstein 2016;Delalande et al 2015;Horodyckid et al 2016;O'Reilly et al 2017;Paefgen et al 2015;Qin et al 2016;Sennoga et al 2016), if additionally desired for the Alzheimer's patient.…”

Microcavitation: the key to modeling blast traumatic brain injury?

“…Efforts by various groups are currently underway for providing high-resolution pathology maps of this new type of cellular injury. In addition to understanding the cavitation damage and resulting neuropathology to the brain tissue itself, several studies have been investigating disruptions in the blood–brain barrier due to cavitation and shock-induced imploding nanobubbles [27,28]. In a recent perspective, for example, Adhikari  et al.…”