Modeling mechanisms of skull base injury for drivers in motor vehicle collisions.

OBJECTIVE: To develop biomechanical variable models for driver skull base injury mechanisms in motor vehicle collisions. STUDY DESIGN: Retrospective database review. METHODS: Biomechanical collision variables and safety restraint data were analyzed for Crash Injury Research and Engineering Network skull base trauma subjects enrolled during the recruitment period between 1996 and 2005. RESULTS: For drivers satisfying inclusion criteria (n = 26), injury resulted from contact with rigid vehicle structural elements in 82%, and occurred in 50% despite both seatbelt and air bags. Eight percent used neither seatbelts nor air bags. Seventy-two percent involved vector velocity changes greater than 30 mph. The relative morbidity of skull base injuries was also detailed. CONCLUSION: The majority of driver skull base injuries resulted from contact with rigid vehicle structural elements in high velocity crashes. Seatbelt and air bag use could not be definitively correlated with skull base injury. CLINICAL SIGNIFICANCE: Injury mechanism models can be developed that facilitate further investigations to determine impact and scope on a national scale.     

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.     

Force Corridors of Post Mortem Human Surrogates in Oblique Side Impacts from Sled Tests

To develop region-specific force corridors in side impacts under oblique loadings using post mortem human surrogates (PMHS). Unembalmed PMHS were positioned on a sled. Surrogates contacted a segmented, modular/ scalable load-wall to isolate region-specific forces (shoulder, thorax, abdomen, pelvis). Heights and widths of segmented load-wall plates were adjustable in sagittal and coronal planes to accommodate anthropometry variations. Load cells were used to gather region-specific forces. Tests were conducted at 6.7 m/s. Peak forces and times of attainments, and standard corridors (mean ± 1 SD) are given for the four torso regions and summated forces. The mean age, stature, and total body mass of the five male PMHS were: 56.6 ± 4.4 years, 183 ± 3.5 cm and 70.6 ± 9.0 kg. Peak pelvis forces were the greatest, followed by thorax, abdomen and shoulder. Sequence of times of attainments of peak forces initiating from pelvis increased rostrally to abdomen to thorax and shoulder regions. Corridors were tight in all regions, except shoulder. As previous force corridors were based solely on pure-lateral impacts and region-specific forces were not extracted, the present oblique responses using anthropometry-specific load-wall design can be used to develop injury criteria and evaluate the biofidelity of dummies.     

Methodology to determine skull bone and brain responses from ballistic helmet-to-head contact loading using experiments and finite element analysis

The objective of the study was to obtain helmet-to-head contact forces from experiments, use a human head finite element model to determine regional responses, and compare outputs to skull fracture and brain injury thresholds. Tests were conducted using two types of helmets (A and B) fitted to a head-form. Seven load cells were used on the head-form back face to measure helmet-to-head contact forces. Projectiles were fired in frontal, left, right, and rear directions. Three tests were conducted with each helmet in each direction. Individual and summated force- and impulse-histories were obtained. Force-histories were inputted to the human head–helmet finite element model. Pulse durations were approximately 4 ms. One-third force and impulse were from the central load cell. 0.2% strain and 40 MPa stress limits were not exceeded for helmet-A. For helmet-B, strains exceeded in left, right, and rear; pressures exceeded in bilateral directions; volume of elements exceeding 0.2% strains correlated with the central load cell forces. For helmet-A, volumes exceeding brain pressure threshold were: 5–93%. All elements crossed the pressure limit for helmet-B. For both helmets, no brain elements exceeded peak principal strain limit. These findings advance our understanding of skull and brain biomechanics from helmet–head contact forces.     

The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation

Phosphorylation of specific sites in the second intracellular loop and in the C-terminal domain have previously been suggested to cause desensitization and internalization of the mu-opioid receptor (MOP-R). To assess sites of MOP-R phosphorylation in vivo, affinity-purified, phosphoselective antibodies were raised against either phosphothreonine-180 in the second intracellular loop (MOR-P1) or the C-terminal domain of MOP-R containing phosphothreonine-370 and phosphoserine-375 (MOR-P2). We found that MOR-P2-immunoreactivity (IR) was significantly increased within the striatum of wild-type C57BL/6 mice after injection of the agonist fentanyl. Pretreatment with the antagonist naloxone blocked the fentanyl-induced increase. Furthermore, mutant mice lacking MOP-R showed only non-specific nuclear MOR-P2-IR before or after fentanyl treatment, confirming the specificity of the MOR-P2 antibodies. To assess whether MOP-R phosphorylation occurs following endogenous opioid release, we induced chronic neuropathic pain by partial sciatic nerve ligation (pSNL), which caused a significant increase in MOR-P2-IR in the striatum. pSNL also induced signs of mu opioid receptor tolerance demonstrated by a rightward shift in the morphine dose response in the tail withdrawal assay and by a reduction in morphine conditioned place preference (CPP). Mutant mice selectively lacking all forms of the beta-endorphin peptides derived from the proopiomelanocortin (Pomc) gene did not show increased MOR-P2-IR, decreased morphine antinociception, or reduced morphine CPP following pSNL. In contrast gene deletion of either proenkephalin or prodynorphin opioids did not block the effects of pSNL. These results suggest that neuropathic pain caused by pSNL in wild-type mice activates the release of the endogenous opioid beta-endorphin, which subsequently induces MOP-R phosphorylation and opiate tolerance.     

The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity,stress, anxiety,mood, and drug dependence

Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995. The generation of specific agonists, antagonists and receptor deficient mice and rats has enabled progress in elucidating the biological functions of N/OFQ. Additionally, radio-imaging technologies have been advanced for investigation of this system in animals and humans. Together with traditional neurobehavioral techniques, these tools have been utilized to identify the biological significance of the N/OFQ system and its interacting partners. The present review focuses on the role of N/OFQ in the regulation of feeding, body weight homeostasis, stress, the stress-related psychiatric disorders of depression and anxiety, and in drug and alcohol dependence. Critical evaluation of the current scientific preclinical literature suggests that small molecule modulators of nociceptin opioid peptide receptors (NOP) might be useful in the treatment of diseases related to these biological functions. In particular, the literature data suggest that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans. However, there are also contradictory data discussed. The current literature on the role of N/OFQ in anxiety and addiction, on the other hand points primarily to a role of agonist modulation being potentially therapeutic. Some drug-like molecules that function either as agonists or antagonists of NOP receptors have been optimized for human clinical study to test some of these hypotheses. The discovery of PET ligands for NOP receptors, combined with the pharmacological tools and burgeoning preclinical data set discussed here bodes well for a rapid advancement of clinical understanding and potential therapeutic benefit.     

Tensile strength of spinal ligaments

Spinal ligaments from 41 fresh human male cadavers were tested. The ligaments were tested in situ by sectioning all elements except the one under study. The force deflection curves demonstrated a sigmoidal shape, and the point at which an increase in deflection was obtained with decreasing force was taken as failure. The force and deformation at failure are shown for each ligament as a function of spinal level.     

Differential sensitivities of mouse strains to morphine and [Dmt1]DALDA analgesia

[Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)), is a highly potent and selective mu-opioid agonist. Nevertheless, systemic [Dmt(1)]DALDA retained its analgesic actions in MOR-1 knockout animals and CXBK mice despite the inactivity of morphine in these mice. [Dmt(1)]DALDA was 6-fold less potent in C57BL/6J mice than in CD-1 mice, whereas morphine potency did not differ between the two strains. Thus, [Dmt(1)]DALDA is a highly selective mu-opioid analgesic with significant pharmacological differences with the prototypic mu-opioid morphine.     

Type II odontoid fracture from frontal impact: case report and biomechanical mechanism of injury

The authors report a case of Type II odontoid fracture from a frontal impact sustained in the crash of a late-model motor vehicle. They discuss the biomechanical mechanisms of injury after considering patient demographic data, type and use of restraint systems including seatbelt and airbags, crash characteristics, and laboratory-based experimental studies. Multiple factors contributed to the Type II odontoid fracture: the patient's tall stature and intoxicated state; lack of manual three-point seat belt use; obliqueness of the frontal impact; and the most likely preflexed position of the head-neck complex at the time of impact, which led to contact of the parietal region with the A-pillar roof-rail area of the vehicle and resulted in the transfer of the dynamic compressive force associated with lateral bending. Odontoid fractures still occur in individuals involved in late-model motor vehicle frontal crashes, and because this injury occurs secondary to head impact, airbags may not play a major role in mitigating this type of trauma to an unrestrained occupant. It may be more important to use seat belts than to depend on the airbag alone for protection from injury.     

Decreased firing frequency of midbrain dopamine neurons in mice lacking mu opioid receptors

Dopamine neurons originating in the midbrain and projecting to cortico-limbic and motor structures are one of the major neuronal substrates implicated in the reinforcing properties of drugs of abuse. The output of this system is largely determined by its impulse activity (amount and pattern of firing activity). Several intrinsic and synaptic factors can influence dopamine neuronal activity and, consequently, addiction liability. Pharmacological studies indicate that mu-opioid receptors and their activation by endogenous opioids may play an important role. In the present study, we use a genetic approach to better understand the role of mu-opioid receptors in modulating dopamine neuronal activity in vivo. Using in vivo extracellular single-unit recordings, we show that mice lacking mu-opioid receptors exhibit lower firing rates of dopamine neurons compared with their wild-type littermates. Although we observed no overall changes in bursting activity compared with wild-type mice, animals lacking mu-opioid receptors exhibited a higher proportion of regular-spiking cells that lacked bursting activity. These findings are the first to emphasize the critical role of mu-opioid receptors in modulating action potential output of dopamine neurons in vivo using a genetic approach. They also provide a possible underlying mechanism for the decreased reinforcing properties of drugs of abuse that was previously observed in mice lacking mu-opioid receptors.