A tissue-level anisotropic criterion for brain injury based on microstructural axonal deformation

Different length scales from micrometers to several decimeters play an important role in diffuse axonal injury. The kinematics at the head level result in local impairments at the cellular level. Finite element methods can be used for predicting brain injury caused by a mechanical loading of the head. Because of its oriented microstructure, the sensitivity of brain tissue to a mechanical load can be expected to be orientation dependent. However, the criteria for injury that are currently used at the tissue level in finite element head models are isotropic and therefore do not consider this orientation dependence, which might inhibit a reliable assessment of injury. In this study, an anisotropic brain injury criterion is developed that is able to describe the effects of the oriented microstructure based on micromechanical simulations. The effects of both the main axonal direction and of local deviations from this direction are accounted for. With the anisotropic criterion for brain injury, computational head models will be able to account for aspects of diffuse axonal injury at the cellular level and can therefore more reliably predict injury.     

人颅骨力学性质的实验研究

本文用颅骨试样进行了准静态下的压缩实验，研究了骨的表观密度、灰度与颅骨力学性质的相关关系，为颅脑损伤分析和模拟试验研究提供了理论依据。     

Optic nerve damage in shaken baby syndrome: detection by beta-amyloid precursor protein immunohistochemistry

BACKGROUND: Rapid acceleration-deceleration of an infant's head during intentional shaking should in theory exert stretch or shear forces upon the optic nerves sufficient to cause axonal injury. beta-Amyloid precursor protein (beta-APP) immunohistochemistry recently has been shown to be a highly effective method for identifying diffuse axonal injury in the brains of infants with shaken baby syndrome. In this study, we investigated the utility of beta-APP in identifying optic nerve damage in infants who have sustained fatal whiplash shaking. MATERIALS AND METHODS: beta-Amyloid precursor protein immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of eyes (including optic disc and distal optic nerve) from infants less than 1 year of age with shaken baby syndrome (5 cases), combined shaken baby syndrome/blunt head trauma (3 cases), and "pure" blunt head trauma (1 case). Nontraumatic control cases included infants who died of suffocation (1 case), sudden infant death syndrome (1 case), and positional asphyxia (1 case) and an enucleation from a child with a retinoblastoma (1 case). Matched hematoxylin-eosin-and neurofilament-stained sections were used for comparison. RESULTS: Three of the 5 shaken baby cases and all 3 combined shaken baby/blunt head trauma cases had optic nerve axonal injury identified by the presence of strongly beta-APP-immunoreactive beaded or swollen axonal segments. Axonal injury could not be detected in the corresponding hematoxylin-eosin-or neurofilament-stained sections. Optic nerve axonal injury was not seen in the case involving pure blunt head trauma or in the nontraumatic control cases. CONCLUSIONS: Optic nerve axonal injury is a prominent feature of intentional fatal whiplash head trauma in infants less than 1 year of age. beta-Amyloid protein precursor immunohistochemistry appears to be the most effective method for demonstrating axonal damage in the optic nerve.     

Evaluation of Three Animal Models for Concussion and Serious Brain Injury

Three animal models were evaluated in this study involving head impacts of the rat, including the Marmarou drop-weight and two momentum-exchange techniques. In series 1, 36 Wistar rats were hit on the side of the free-moving head using Marmarou’s 450 g impact mass at 4.4, 5.4, and 6.3 m/s. Head acceleration was measured and injuries were observed. The 6.3-m/s side impact resulted in no deaths, no skull fractures, infrequent contusions, and some injuries consistent with diffuse axonal injury. In series 2, 57 Marmarou drop-weight tests were conducted to study head biomechanical responses. Marmarou’s technique involves a head impact followed by prolonged loading into a foam pad under the animal. Based on the literature, the 2 m (6.3 m/s) Marmarou drop causes death, skull fracture, brain and spinal cord contusions, and diffuse axonal injury. These injuries are more severe than that occurring with impact of similar mass and velocity to the free-moving head. Impacts to the free-moving head provide more realistic animal models to study concussion and severe brain injury.     

Diffuse axonal injury in head injury: definition, diagnosis and grading

Diffuse axonal injury is one of the most important types of brain damage that can occur as a result of non-missile head injury, and it may be very difficult to diagnose post mortem unless the pathologist knows precisely what he is looking for. Increasing experience with fatal non-missile head injury in man has allowed the identification of three grades of diffuse axonal injury. In grade 1 there is histological evidence of axonal injury in the white matter of the cerebral hemispheres, the corpus callosum, the brain stem and, less commonly, the cerebellum; in grade 2 there is also a focal lesion in the corpus callosum; and in grade 3 there is in addition a focal lesion in the dorsolateral quadrant or quadrants of the rostral brain stem. The focal lesions can often only be identified microscopically. Diffuse axonal injury was identified in 122 of a series of 434 fatal non-missile head injuries--10 grade 1, 29 grade 2 and 83 grade 3. In 24 of these cases the diagnosis could not have been made without microscopical examination, while in a further 31 microscopical examination was required to establish its severity.     

Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining

OBJECTIVE: Accurate identification of diffuse axonal injury is important in the forensic investigation of infants who have died from traumatic brain injury. beta-Amyloid precursor protein (beta-APP) immunohistochemical staining is highly sensitive in identifying diffuse axonal injury. However, the effectiveness of this method in brain-injured infants has not been well established. The present study was undertaken to assess the utility of beta-APP immunohistochemistry in detecting diffuse axonal injury in infants with either shaken baby syndrome or blunt head trauma. MATERIALS AND METHODS: Archival formalin-fixed, paraffin-embedded blocks from infants (<1 year old) with shaken baby syndrome (7 cases) and blunt head trauma (3) and blocks from 7 control cases that included nontraumatic cerebral edema (1), acute hypoxic-ischemic encephalopathy (1), and normal brain (5) were immunostained for beta-APP. A semiquantitative assessment of the severity of axonal staining was made. Corresponding hematoxylin-eosin-stained sections were examined for the presence of axonal swellings. RESULTS: Immunostaining for beta-APP identified diffuse axonal injury in 5 of 7 infants with shaken baby syndrome and 2 of 3 infants with blunt head trauma. Immunoreactive axons were easily identified and were present in the majority of the sections examined. By contrast, hematoxylineosin staining revealed axonal swellings in only 3 of 7 infants with shaken baby syndrome and 1 of 3 infants with blunt head trauma. Most of these sections had few if any visible axonal swellings, which were often overlooked on initial review of the slides. No beta-APP immunoreactivity was observed in any of the 7 control cases. CONCLUSIONS: Immunostaining for beta-APP can easily and reliably identify diffuse axonal injury in infants younger than 1 year and is considerably more sensitive than routine hematoxylin-eosin staining. We recommend its use in the forensic evaluation of infants with fatal craniocerebral trauma.     

Rheological properties of the tissues of the central nervous system: a review

Knowledge of the biomechanical properties of central nervous system (CNS) tissues is important for understanding mechanisms and thresholds for injury, and aiding development of computer or surrogate models of these tissues. Many investigations have been conducted to estimate the properties of CNS tissues including under shear, compressive and tensile loading, however there is much variability in this body of literature, making it difficult to separate the material properties from effects that result from a given experimental protocol. This review summarises previous studies of brain and spinal cord properties; discussing their main findings and points of difference, and displays the reported data on comparable scales. Additionally, based on the observed effects of methodological choices on reported tissue properties, recommendations for future studies of brain and spinal cord properties are made.     

Mechanical Performance of Cranial Bone in Impact Protection of Woodpecker Brain:A Finite Element Study

Human head impact injuries caused by a sudden impact force are very common in aviation lifesaving,car crash accident,war or sports activities. Yet,an intriguing example of nature is woodpecker which is free from head injury even it drums trunk continually at a speed of about 6-7 m/s and a deceleration of about 1000 g.Woodpecker must have special characteristics to attenuate repetitive impact force to sustain rapid pecking without brain injury. In this study,the effect of mechanical property of cranial bone on the brain during impact was investigated using the finite element(FE)approach. It was demonstrated that the pressure,Von-Mises stresses and shear stress at the same point on the posterior of woodpecker's brain were decreased greatly compared with hoopoe and lark. It was stated that the higher strength of woodpecker's cranial bone might play an important role for preventing woodpecker's head injury.     

Finite-element models of the human head

A review is presented of the existing finite-element (FE) models for the biomechanics of human head injury. Finite element analysis can be an important tool in describing the injury biomechanics of the human head. Complex geometric and material properties pose challenges to FE modelling. Various assumptions and simplifications are made in model development that require experimental validation. More recent models incorporate anatomic details with higher precision. The cervical vertebral column and spinal cord are included. Model results have been more qualitative than quantitative owing to the lack of adequate experimental validation. Advances include transient stress distribution in the brain tissue, frequency responses, effects of boundary conditions, pressure release mechanism of the foramen magnum and the spinal cord, verification of rotation and cavitation theories of brain injury, and protective effects of helmets. These theoretical results provide a basic understanding of the internal biomechanical responses of the head under various dynamic loading conditions. Basic experimental research is still needed to determine more accurate material properties and injury tolerance criteria, so that FE models can fully exercise their analytical and predictive power for the study and prevention of human head injury.     

An experimental study on the biomechanical properties of the cancellous bones of distal femur

OBJECTIVES: To study the comprehensive biomechanical properties of the cancellous bone of distal femur through a series of mechanical tests, and provide relevant subjects with the basic technical data. BACKGROUNDS: The study on bone mechanics is a commonly used approach to evaluate the biomechanical competency of bone. The biomechanical properties of bone have come to be the precondition of the further research of these relevant clinical subjects. METHODS: In this paper, comprehensive items of mechanical properties of the cancellous bones of distal femur were conducted, and many valuable test results were obtained through a series of mechanical tests, which comprised tensile test, compression test, torsion test, shear test, bending test and impact test. The specimens were extracted from the normal corpses of Chinese donors died from acute head injury. As another key problem in this kind of experiment, the sampling and fixing method of cancellous bones specimens was developed and optimized in this research. RESULTS: A series of the experimental data of mechanical properties of cancellous bones were obtained in the tests, these experimental data include tensile strength, compression strength, yield tensile strength, modulus of elasticity, torsion strength, shear strength, torsion modulus, bending strength, yield shear limit and impact toughness, which can reflect the complex mechanical competency of bone, being of great value and practice in clinic and further research on cancellous bones. The mechanical properties of the cancellous bones of distal femur were analyzed and discussed. CONCLUSIONS: The biomechanical properties of the cancellous bones have a close relationship with individual difference. Comprehensive items of the mechanical properties of the bone can evaluate the mechanical performance of the bone better, and can provide more valuable data to relevant research.     

关于头部组织材料性能敏感性对颅内压力响应的研究

应用有限元法 (finiteelementmethod)和试验设计技术 (design of experimentDOE)研究人头部颅骨(skull)、脑脊液 (cerebral spinal fluidCSF)和脑髓 (brain)材料性能的敏感性对颅内因撞击而产生的压力响应。该研究采用头部的有限元模型 ,用三因子、三层次的因子试验设计对影响颅内因撞击而引起的压力的颅骨、脑脊液和脑髓的材料性质的敏感性进行分析。研究结果进一步证实了颅骨、脑脊液、脑髓的材料性能对颅内因撞击而引起的压力的重要影响。本研究为进一步的头部的有限元分析提供了新的见解 ,并提出了对头部组织的材料性能作更进一步的探索。     

Unilateral Hypoglossal Nerve Injury in a Collegiate Wrestler: A Case Report

Objective:

To introduce the case of a collegiate wrestler who suffered a traumatic unilateral hypoglossal nerve injury. This case presents the opportunity to discuss the diagnosis and treatment of a 20-year-old man with an injury to his right hypoglossal nerve.

Background:

Injuries to the hypoglossal nerve (cranial nerve XII) are rare. Most reported cases are the result of malignancy, with traumatic causes less common. In this case, a collegiate wrestler struck his head on the wrestling mat during practice. No loss of consciousness occurred. The wrestler initially demonstrated signs and symptoms of a mild concussion, with dizziness and a headache. These concussion symptoms cleared quickly, but the athlete complained of difficulty swallowing (dysphagia) and demonstrated slurred speech (dysarthria). Also, his tongue deviated toward the right. No other neurologic deficits were observed.

Differential Diagnosis:

Occipital-cervical junction fracture, syringomyelia, malignancy, iatrogenic causes, cranial nerve injury.

Treatment:

After initial injury recognition, the athletic trainer placed the patient in a cervical collar and transported him to the emergency department. The patient received prednisone, and the emergency medicine physician ordered cervical spine plain radiographs, brain computed tomography, and brain and internal auditory canal magnetic resonance imaging. The physician consulted a neurologist, who managed the patient conservatively, with rest and no contact activity. The neurologist allowed the patient to participate in wrestling 7 months after injury.

Uniqueness:

To our knowledge, no other reports of unilateral hypoglossal nerve injury from relatively low-energy trauma (including athletics) exist.

Conclusions:

Hypoglossal nerve injury should be considered in individuals with head injury who experience dysphagia and dysarthria. Athletes with head injuries require cranial nerve assessments.     

The possible role of hypoxia in the formation of axonal bulbs.

AIMS: To assess the possible role of hypoxia in the formation of axonal bulbs. METHODS: Study material comprised sections from 28 brains showing evidence of cerebral hypoxia with no history of head injury, four with a history of head trauma but no evidence of hypoxic change, eight with a history of head trauma and hypoxic change, and four from control brains originally described as "diffuse axonal injury." These were subjected to microwave antigen retrieval and immunohistochemistry using monoclonal antibodies to beta amyloid precursor protein (beta APP), glial fibrillary acid protein (GFAP), and CD68-PGM1. RESULTS: Positive staining for beta APP was seen in all four controls, all four cases of head injury only, seven of eight cases of head injury and hypoxic changes, and 12 of 28 cases of hypoxia without history of head injury; 22 of 25 cases who had been ventilated showed positive staining. The majority of cases showed evidence of cerebral swelling. CONCLUSIONS: Axonal bulbs staining positively for beta APP may occur in the presence of hypoxia and in the absence of head injury. The role of hypoxia, raised intracranial pressure, oedema, shift effects, and ventilatory support in the formation of axonal bulbs is discussed. The presence of axonal bulbs cannot necessarily be attributed to shearing forces alone.     

Traumatically induced axonal injury: pathogenesis and pathobiological implications.

This work reviews the pathobiology of traumatically induced axonal injury. Drawing upon literature gleaned from the experimental and clinical setting, this review attempts to emphasize that, other than the most destructive insults, traumatic brain injury does not typically cause direct mechanical disruption of the axon. Rather, this review documents that with traumatic injury focal, subtle axonal change occurs, and that over time, such change leads to impaired axoplasmic transport, continued axonal swelling, and ultimate disconnection. The initial intra-axonal events that trigger the above described sequence of reactive axonal change are considered with focus on the possibility of either traumatically altered axolemmal permeability, direct cytoskeletal damage/perturbation, or more overt metabolic/functional disturbances. Not only does this review focus on the sequence of traumatically induced axonal change, but also, it considers its attendant consequences in terms of Wallerian degeneration and subsequent deafferentation. The concept that traumatically induced diffuse axonal injury leads to diffuse deafferentation is emphasized together with its pathobiological implications for morbidity and recovery. The potential for either adaptive or maladaptive neuroplasticity subsequent to such diffuse deafferentation is considered in the context of mild, moderate and severe traumatic brain injury.     

Diffuse axonal injury induced by simultaneous moderate linear and angular head accelerations in rats

Diffuse axonal injury (DAI) is one of the most common and important pathologic features of human traumatic brain injury (TBI), accounting for high mortality and development of persistent post-traumatic neurologic sequelae. Although a relatively high number of therapies have been shown to be effective in experimental models, there are currently few treatments that are effective for improving the prognosis of clinical DAI. A major reason is the failure of current models to validly reproduce the pathophysiological characteristics observed after clinical DAI. In the present study, we employed a specially designed, highly controllable model to induce a sudden rotation in the coronal plane (75 degrees rotation at 1.6×10⁴ degrees/s) combined with lateral translation (1.57 cm displacement at 3.4×10² cm/s) to the rat's head. We were interested in discovering whether the combined accelerations could reproduce the pathophysiological changes analogous to those seen in human DAI. The axonal injury as assessed with amyloid protein precursor (APP) as a marker was consistently present in all injured rats. The commonly injured brain regions included the subcortical regions, deep white matter, corpus callosum and brain stem. The evolution of APP accumulations in brain sections depicted the detailed progression of axonal pathology. Ultrastructural studies gave further insights into the presence and progression of axonal injury. All injured rats exhibited transient physiological dysfunction, as well as immediate and dramatic neurological impairment that still persisted at 14 days after injury. These results suggest that this model reproduced the major pathophysiological changes analogous to those observed after severe clinical TBI and provides an attractive vehicle for experimental brain injury research.     

Regional variations in the viscoelastic compressive properties of the temporomandibular joint disc and implications toward tissue engineering

Evidence from experimental and finite element studies have shown that the temporomandibular joint disc is heavily loaded during normal physiological function. Several studies have been carried out to investigate the response of the disc to tensile and static compressive forces. However, there is limited information that elucidates the dynamic characteristics of the disc under in vivo loading conditions. These investigations assessed the effect of physiologically relevant applied strain amplitudes and frequencies to determine regional mechanical properties of the disc. Cyclic tests on porcine TMJ discs were carried out over a period of 15 cycles, and the resultant compressive moduli and energy dissipation properties of the disc were reported. Results showed that modulus values were more dependent on strain amplitude than on frequency, and modulus values exhibited a strong regional variation. Clear hysteresis loops were evident in each set of testing parameters, and the only statistically significant regional variation in energy dissipation was between the central and medial regions. From these investigations, a more detailed understanding of the spatial mechanical properties of the TMJ disc has been achieved under physiologically relevant loading conditions. Combined with studies on other loading modalities of the disc, these results will serve as a benchmark for future TMJ disc tissue engineering endeavors.     

Material properties of trabecular bone structures

Abstract: The transplantation of human allograft for restoration and filling of cortical bone defects is well known. Our aim was an experimental investigation of the mechanical stability of the often used femoral head spongiosa depending on the caliber and extent of the allograft. To evaluate the orientation of the trabecular structures of the femoral head and relate this data to its mechanical properties, morphometric studies were combined with mechanical tests of cancellous bone specimens. The mechanical examination of the allograft was done following the compression test according to DIN 50106. We examined 36 human unfixed hip joint spongiosa cylinders with a height of 11 mm and a diameter of 24 mm. We took three specimens from each femoral head. We compressed the allograft at a constant velocity of 0.017 mm/sec. We calculated the maximum compression strength, the yield point and the Young’s modulus. We also examined 12 parallelepipedic specimens with (17 × 17 × 51 mm) for morphometric analysis and loading in the direction of the primary compressive group (PCG), as well as perpendicular loading and at an angle of 45°. We found divergent mechanical stabilities. None of the femoral heads showed comparable compressive strength. There was no position dependency of the strength of the samples. No relation between optical appearance and strength was found. We found a value for the lower compressive strength, which can be used for calculation as a basic value for safe constructions. Furthermore we tested the well known dependence of strength on the direction of the trabecular structure. We found a strong relationship between strength and load direction on the preferred direction of the trabecular structure. The sole recommendation resulting from our investigations is to rely on the lowest compressive strength for all preoperative planning. Relying on higher compressive strength by using the theoretical predicted areas of higher strength is hazardous since we found no correlation between position of sampling and strength. The size of our samples is important, because of the fact that different sizes of the samples might cause different failure mechanisms in the samples. The preparation of the femoral head spongiosa should be done according to the primary compressive group of the trabecular structure.     

Articular cartilage biomechanics: theoretical models, material properties, and biosynthetic response

Articular cartilage has unique material properties that enable the cartilage to perform its physiological functions over a lifetime and under a wide range of loading conditions. Numerous studies have investigated the relationship between cartilage properties and composition/structure. For cartilage transplantation and regeneration, it is necessary to know how cartilage maintains its functionality and how cartilage responds to the ever-changing mechanical environment. In this review, we discuss theoretical and experimental studies on the behavior of articular cartilage to load. In the first part, the composition and structure of articular cartilage is presented. In the second part, theoretical models of the mechanical behavior of cartilage, experimental methods for the determination of cartilage properties, and material properties for normal, pathologic, and repair cartilage are summarized. In the third part, the relationship between mechanical loading of the cells and their corresponding biological responses are discussed. The goal for treating joint degeneration in the future lies in cartilage regeneration rather than prosthetic replacement. In order to achieve this goal, it has to be understood how structure and function, metabolic and biochemical properties, and biomechanical performance of articular cartilage can be restored.     

Development and Functional Organization of the Cranial Nerves in Lampreys

Lampreys, together with hagfishes, are the only extant representatives of the oldest branch of vertebrates, the agnathans, which are the sister group of gnathostomes; therefore, studies on these animals are of great evolutionary significance. Lampreys exhibit a particular life cycle with remarkable changes in their behavior, concomitant, in part, with important modifications in the head and its musculature, which might influence the development of the cranial nerves. In this context, some cranial nerves such as the optic nerve and the ocular motor nerves, which develop slowly during an extremely long larval period lasting more than five years, have been more thoroughly investigated; however, much less experimental information is available about others, such as the facial or the hypoglossal nerves. In addition, the possible existence of a “true” accessory nerve in these animals is still a matter of conjecture. Although growing in last decades, investigations on the physiology of the lamprey cranial nerves is scanty. This review focuses on past and recent findings that have contributed to characterize the anatomical organization of the cranial nerves in lampreys, including their components and nuclei, and their relations in the brain; in addition, comments on their development and functional role are also included. Anat Rec, 302:512–539, 2019. © 2018 Wiley Periodicals, Inc.