A study on the diagnostic support system of the repetitive brain concussion based on the reconstruction analysis of the accident.

In this paper the effectiveness of the support system which predicts the risk of the repetitive brain concussion is studied biomechanically. In the risk prediction system, the accident that caused the concussion is reconstructed by analyzing the game video via multibody dynamics and the resulting brain injury is calculated in detail by the finite element method. In order to calculate the aggravation of the brain injury by the repeated brain concussion, the following two methods are examined. In the first method, the material properties of the part of the brain damaged by the1st impact are changed in the simulation of the 2nd impact. In the second method, each brain damage caused by the repeated impacts is accumulated. The system was applied to the real-life accidents that occurred during Judo and American football games. As a result of the simulations, the aggravation of the brain damage due to repetitive concussion was determined numerically in terms of the maximum strain of the brain and the brain damage rate of the whole brain. The biomechanical process of the collision accidents and the resulting brain damage were reconstructed based on the video and the results are effective to prevent the future repeated concussion accidents. J. Med. Invest. 70 : 213-220, February, 2023.

Strain-Rate Dependency of Axonal Tolerance for Uniaxial Stretching.

This study aims to clarify the relation between axonal deformation and the onset of axonal injury. Firstly, to examine the influence of strain rate on the threshold for axonal injury, cultured neurons were subjected to 12 types of stretching (strains were 0.10, 0.15, and 0.20 and strain rates were 10, 30, 50, and 70 s-1). The formation of axonal swellings and bulbs increased significantly at strain rates of 50 and 30 s-1 with strains of 0.15 and 0.20, respectively, even though those formations did not depend on strain rates in cultures exposed to a strain of 0.10. Then, to examine the influence of the strain along an axon on axonal injury, swellings were measured at every axonal angle in the stretching direction. The axons that were parallel to stretching direction were injured the most. Finally, we proposed an experimental model that subjected an axon to more accurate strain. This model observed the process of axonal injury formation by detecting the same neuron before and after stretching. These results suggest that the strain-rate dependency of axonal tolerance is induced by a higher magnitude of loading strain and an experiment focusing on axonal strain is required for obtaining more detailed injury criteria for an axon.

In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats.

Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways.

Effect of amplitude and duration of impulsive pressure on endothelial permeability in in vitro fluid percussion trauma.

BACKGROUND: Intracranial pressure changes during head impact cause brain injuries such as vasogenic edema and cerebral contusion. However, the influence of impulsive pressure on endothelial function has not yet been fully studied in vitro. In this study, we developed a pressure loading device that produced positive and negative pressures by modifying an in vitro fluid percussion model and examined the effects of the amplitude and duration of the pressures on endothelial permeability. METHODS: Human umbilical vein endothelial cells were subjected to three types of positive pressure (average amplitude/average duration of 352 kPa/23 ms, 73 kPa/27 ms, and 70 kPa/44 ms) and three types of negative pressure (-72 kPa/41 ms, -67 kPa/104 ms, and -91 kPa/108 ms), and the transendothelial electrical resistance (TEER) was measured between 15 min and 24 h after pressure loading for quantifying the formation of an integral monolayer of endothelial cells. After loading, vascular endothelial- (VE-) cadherin, an endothelium-specific cell-cell adhesion molecule involved in endothelial barrier function, was stained and observed using fluorescence microscopy. RESULTS: The pressure loading device could produce positive pressure pulses with amplitudes of 53-1348 kPa and durations of 9-29.1 ms and negative pressure pulses with amplitudes of -52 - -93 kPa and durations of 42.9-179.5 ms. The impulsive pressure reduced the TEER associated with the change in VE-cadherin localization. Additionally, TEER decreased considerably at 15 min and 6 h post-loading, with these changes being significant in positive pressure with larger amplitude and shorter duration and in all types of negative pressures compared to pre-loading. CONCLUSIONS: The changes in intracranial pressure during head impact impair endothelial barrier function by the disruption of the integrity of endothelial cell-cell junctions, and the degree of increase in endothelial permeability depends on the amplitude, duration, and direction (compressive and tensile) of the impulsive pressure.

Combinations of hydrostatic pressure and shear stress influence morphology and adhesion molecules in cultured endothelial cells.

Endothelial cells are exposed to mechanical stimuli from blood flow and blood pressure. However, it is not yet fully understood how their simultaneous exposure affects endothelial function. Firstly, in this study we investigated the effect of combined stress on morphology of cultured human aortic endothelial cells (HAECs). In the results, HAECs exposed to steady flow (a pressure of 100 mmHg, and a shear stress of 1.5 Pa) were more elongated than those exposed to a hydrostatic pressure of 100 mmHg and HAECs exposed to pulsatile flow (a pressure of 80/120 mmHg, and a shear stress of 1.2/1.8 Pa) were more elongated than those exposed to steady flow. Similarly, HAECs exposed to pulsatile flow were most oriented to the flow direction among these three stresses. Secondly, we investigated the effect of combined stress on gene expression of cell adhesion molecules in HAECs. After stress exposure to HAECs the mRNA of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were measured by real time RT-PCR. In the results, the exposure of steady flow increased the mRNA levels of ICAM-1 compared to the exposure of hydrostatic pressure; however, the exposure of pulsatile flow decreased the mRNA level of ICAM-1 compared to the exposure of steady flow. These findings suggest that gene expression of cell adhesion molecules induced by combined stress were different to the superposition of individual stress and that not only difference in the components of combined stress but also difference in the magnitude of the components of combined stress are important.

Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage.

OBJECTIVE: Pathophysiology after subarachnoid hemorrhage (SAH) caused by aneurysmal rupture has not been well examined. The purpose of this study was to observe platelet-leukocyte-endothelial cell interactions as indexes of inflammatory and prothrombogenic responses in the acute phase of SAH, using an in vivo cranial window method. METHODS: Subarachnoid hemorrhage was induced in C57Bl/6J mice by using the endovascular perforation method. Intravital microscopy was used to monitor the rolling and adhesion of platelets and leukocytes that were labeled with different fluorochromes. Regional cerebral blood flow was measured with laser Doppler flowmetry. The platelet-leukocyte-endothelial cell interactions were observed 30 minutes, 2 hours, and 8 hours after SAH. The effect of P-selectin antibody and apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, on these responses was examined at 2 hours after SAH, and compared with a different SAH model in which autologous blood was injected into the foramen magna. RESULTS: SAH was accompanied by a 60% decrease in regional cerebral blood flow, whereas no changes in regional cerebral blood flow were observed on the contralateral side. SAH elicited time- and size-dependent increases in rolling and adherent platelets and leukocytes in cerebral venules. All of these interactions were attenuated by treatment with a P-selectin antibody or apocynin. There was no significant blood cell recruitment observed in the blood-injected SAH model. CONCLUSION: SAH at the skull base induced P-selectin- and oxygen radical-mediated platelet-leukocyte-endothelial cell interactions in venules at the cerebral surface. These early inflammatory and prothrombogenic responses may cause a whole-brain injury immediately after SAH.

Angiotensin II type 1 receptor signaling contributes to platelet-leukocyte-endothelial cell interactions in the cerebral microvasculature.

Angiotensin II type 1 (AT(1)) receptor signaling has been implicated in cerebral microvascular alterations associated with ischemia, diabetes mellitus, hypercholesterolemia, and atherosclerosis. Platelets, which express AT(1) receptors, also appear to contribute to the thrombogenic and inflammatory responses that are elicited by these pathological conditions. This study assesses the role of AT(1) receptor activation on platelet-leukocyte-endothelial cell interactions elicited in cerebral microvasculature by ischemia and reperfusion. Intravital microscopy was used to monitor the adhesion of platelets and leukocytes that were labeled with different fluorochromes, whereas dihydrorhodamine-123 was used to quantify oxygen radical production in cerebral surface of mice that were either treated with the AT(1) receptor agonist Val-angiotensin II (ANG II) or subjected to bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. ANG II elicited a dose- and time- dependent increase in platelet-leukocyte-endothelial cell interactions in cerebral venules that included rolling platelets, adherent platelets on the leukocytes and the endothelial cells, rolling leukocytes, and adherent leukocytes. All of these interactions were attenuated by treatment with either P-selectin or P-selectin glycoprotein ligand 1 (PSGL-1) antibody. The AT(1) receptor antagonist candesartan and losartan as well as diphenyleneiodonium, an inhibitor of flavoproteins including NAD(P)H oxidase, significantly reduced the platelet-leukocyte-endothelial cell interactions elicited by either ANG II administration or BCCAO/reperfusion. The increased oxygen radical generation elicited by BCCAO/reperfusion was also attenuated by candesartan. These findings are consistent with an AT(1) receptor signaling mechanism, which involves oxygen radical production and ultimately results in P-selectin- and PSGL-1-mediated platelet-leukocyte-endothelial cell interactions in the cerebral microcirculation.