Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

Motor slowing, forebrain white matter loss, and striatal shrinkage have been reported in premanifest Huntington’s disease (HD) prior to overt striatal neuron loss. We carried out detailed LM and EM studies in a genetically precise HD mimic, heterozygous Q140 HD knock-in mice, to examine the possibility that loss of corticostriatal and thalamostriatal terminals prior to striatal neuron loss underlies these premanifest HD abnormalities. In our studies, we used VGLUT1 and VGLUT2 immunolabeling to detect corticostriatal and thalamostriatal (respectively) terminals in dorsolateral (motor) striatum over the first year of life, prior to striatal projection neuron pathology. VGLUT1+ axospinous corticostriatal terminals represented about 55% of all excitatory terminals in striatum, and VGLUT2+ axospinous thalamostriatal terminals represented about 35%, with VGLUT1+ and VGLUT2+ axodendritic terminals accounting for the remainder. In Q140 mice, a significant 40% shortfall in VGLUT2+ axodendritic thalamostriatal terminals and a 20% shortfall in axospinous thalamostriatal terminals was already observed at 1 month of age, but VGLUT1+ terminals were normal in abundance. The 20% deficiency in VGLUT2+ thalamostriatal axospinous terminals persisted at 4 and 12 months in Q140 mice, and an additional 30% loss of VGLUT1+ corticostriatal terminals was observed at 12 months. The early and persistent deficiency in thalamostriatal axospinous terminals in Q140 mice may reflect a development defect, and the impoverishment of this excitatory drive to striatum may help explain early motor defects in Q140 mice and in premanifest HD. The loss of corticostriatal terminals at 1 year in Q140 mice is consistent with prior evidence from other mouse models of corticostriatal disconnection early during progression, and can explain both the measurable bradykinesia and striatal white matter loss in late premanifest HD.

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During the micromachining processes of particle-reinforced metal matrix composites (PMMCs), matrix-particle interface failure plays an important role in the cutting mechanism. This paper presents a novel analytical model to predict the cutting forces in micromilling of this material considering particle debonding caused by interface failure. The particle debonding is observed not only in the processed surface but also in the chip. A new algorithm is proposed to estimate the particles debonding force caused by interface failure with the aid of Nardin–Schultz model. Then, several aspects of the cutting force generation mechanism are considered in this paper, including particles debonding force in the shear zone and build-up region, particles cracking force in the build-up region, shearing and ploughing forces of metal matrix, and varying sliding friction coefficients due to the reinforced particles in the chip-tool interface. The micro-slot milling experiments are carried out on a self-made three-axis high-precision machine tool, and the comparison between the predicted cutting forces and measured values shows that the proposed model can provide accurate prediction. Finally, the effects of interface failure, reinforced particles, and tool edge radius on cutting forces are investigated by the proposed model and some conclusions are given as follows: the particles debonding force caused by interface failure is significant and takes averagely about 23% of the cutting forces under the given cutting conditions; reinforced particles and edge radius can greatly affect the micromilling process of PMMCs.

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