Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

White matter injury induced by ischemic stroke elicits sensorimotor impairments, which can be further deteriorated by persistent proinflammatory responses. We previously reported that delayed and repeated treatments with omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve spatial cognitive functions and hippocampal integrity after ischemic stroke. In the present study, we report a post-stroke n-3 PUFA therapeutic regimen that not only confers protection against neuronal loss in the gray matter but also promotes white matter integrity. Beginning 2 hours after 60 minutes of middle cerebral artery occlusion (MCAO), mice were randomly assigned to receive intraperitoneal docosahexaenoic acid (DHA) injections (10 mg/kg, daily for 14 days), alone or in combination with dietary fish oil (FO) supplements starting 5 days after MCAO. Sensorimotor functions, gray and white matter injury, and microglial responses were examined up to 28 days after MCAO. Our results showed that DHA and FO combined treatment facilitated long-term sensorimotor recovery and demonstrated greater beneficial effect than DHA injections alone. Mechanistically, n-3 PUFAs not only offered direct protection on white matter components, such as oligodendrocytes, but also potentiated microglial M2 polarization, which may be important for white matter repair. Notably, the improved white matter integrity and increased M2 microglia were strongly linked to the mitigation of sensorimotor deficits after stroke upon n-3 PUFA treatments. Together, our results suggest that post-stroke DHA injections in combination with FO dietary supplement benefit white matter restoration and microglial responses, thereby dictating long-term functional improvements.

Traumatic brain injury (TBI) is one of the most disabling clinical conditions that could lead to neurocognitive disorders in survivors. Our group and others previously reported that prophylactic enrichment of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) markedly ameliorate cognitive deficits after TBI. However, it remains unclear whether a clinically relevant therapeutic regimen with n-3 PUFAs administered after TBI would still offer significant improvement of long-term cognitive recovery. In the present study, we employed the decline of spatial cognitive function as a main outcome after TBI to investigate the therapeutic efficacy of post-TBI n-3 PUFA treatment and the underlying mechanisms. Mice were subjected to sham operation or controlled cortical impact, followed by random assignment to receive the following four treatments: (1) vehicle control; (2) daily intraperitoneal injections of n-3 PUFAs for 2 weeks, beginning 2 h after TBI; (3) fish oil dietary supplementation throughout the study, beginning 1 day after TBI; or (4) combination of treatments (2) and (3). Spatial cognitive deficits and chronic brain tissue loss, as well as endogenous brain repair processes such as neurogenesis, angiogenesis, and oligodendrogenesis, were evaluated up to 35 days after TBI. The results revealed prominent spatial cognitive deficits and massive tissue loss caused by TBI. Among all mice receiving post-TBI n-3 PUFA treatments, the combined treatment of fish oil dietary supplement and n-3 PUFA injections demonstrated a reproducible beneficial effect in attenuating cognitive deficits although without reducing gross tissue loss. Mechanistically, the combined treatment promoted post-TBI restorative processes in the brain, including generation of immature neurons, microvessels, and oligodendrocytes, each of which was significantly correlated with the improved cognitive recovery. These results indicated that repetitive and prolonged n-3 PUFA treatments after TBI are capable of enhancing brain remodeling and could be developed as a potential therapy to treat TBI victims in the clinic.

Prophylactic dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to remarkably ameliorate ischemic brain injury. However, the therapeutic efficacy of n-3 PUFA administration post stroke, especially its impact on neurovascular remodeling and long-term neurological recovery, has not been fully characterized thus far. In this study, we investigated the effect of n-3 PUFA supplementation, as well as in combination with docosahexaenoic acid (DHA) injections, on long-term stroke outcomes. Mice were subjected to transient middle cerebral artery occlusion (MCAO) before randomly assigned to 4 groups to receive: 1) low dose of n-3 PUFAs as the vehicle control; 2) intraperitoneal DHA injections; 3) n-3 PUFA dietary supplement; or 4) combined treatment of 2) and 3). Neurological deficits and brain atrophy, neurogenesis, angiogenesis, and glial scar formation were assessed up to 28 days after MCAO. Results revealed that groups 2 and 3 showed only marginal reduction in post-stroke tissue loss and attenuation of cognitive deficits. Interestingly, group 4 exhibited significantly reduced tissue atrophy and improved cognitive functions compared to groups 2 and 3 with just a single treatment. Mechanistically, the combined treatment promoted post-stroke neurogenesis and angiogenesis, and reduced glial scar formation, all of which significantly correlated with the improved spatial memory in the Morris water maze. These results demonstrate an effective therapeutic regimen to enhance neurovascular restoration and long-term cognitive recovery in the mouse model of MCAO. Combined post-stroke DHA treatment and n-3 PUFA dietary supplementation thus may be a potential clinically-translatable therapy for stroke or related brain disorders.

Traumatic brain injury (TBI) is a major cause of death and disability in young adults. Long-term mental disability often occurs in patients suffering moderate and severe TBI while not as frequent in the victims of mild TBI. To explore the potential mechanism underlying this severity-dependent cognitive deficit, we subjected C57/BL6 mice to different severities of controlled cortical impact (CCI) and assessed their learning-memory functions. The mice subjected to moderate and severe TBI exhibited significantly impaired long-term spatial learning-memory ability, which was accompanied by marked white matter injury and hippocampus damage. In contrast, long-term learning-memory deficits or structural abnormalities within the hippocampus or white matter were not significant in the case of mild TBI. According to a correlation analysis, the hippocampus or white matter injury severity was more relevant to Morris water maze outcome than tissue volume. This study revealed that long-term spatial learning-memory deficits are dependent on the severity of destruction in the white matter and hippocampus. Therapeutic strategies targeting both the white matter and hippocampus may be needed to improve the neurological functions in TBI victims.

Although a variety of animal models of atherosclerosis have been developed, these models are time-consuming and costly. Here, we describe an in vitro model to induce foam cell formation in the early stage of atherosclerosis. This model is based on a three-dimension co-culture system in a stretchable microfluidic device. An elastic membrane embedded in the microfluidic device is capable of delivering nonuniform strain to vascular smooth muscle cells, endothelial cells and monocytes adhering thereto, which are intended to mimic the biological environment of blood vessels. Under low-density lipoprotein and stretch treatment, foam cell formation was successfully induced in co-culture with changes in mRNA and protein expression of some related key factors. Subsequently, the model was used to assess the inhibitory effect of atorvastatin on foam cell formation. The results obtained indicate that atorvastatin has a significantly dose-dependent inhibition of foam cell formation, which can be explained by the changes in mRNA and protein expression of the related factors. In principle, the model can be used to study the role of different types of cells in the formation of foam cells, as well as the evaluation of anti-atherosclerotic drugs.

Magnesium (Mg) and its alloys are promising candidates for use as resorbable materials for biomedical devices that can degrade in situ following healing of the defect, eliminating the need for a second surgery to remove the device. Hydrogen gas is the main product of magnesium corrosion, and one of the limitations for use of Mg devices in clinic is the formation of gas pockets around them. One potential solution to this problem is reducing the rate of corrosion to the levels at which H 2 can diffuse through the body fluids. The study's aim was to evaluate the potential of hybrid alkylsilane self-assembled multilayer coatings to reduce Mg corrosion and to modify physicochemical properties of the coatings using surface functionalization. The coating was made by copolymerization of n-Decyltriethoxysilane and Tetramethoxysilane followed by dip coating of metal discs. This resulted in a formation of homogeneous, micron thick, and defect free coating. The coated surface was more hydrophobic than bare Mg, however functionalization of the coating with 3-aminopropyltriethoxysilane reduced the hydrophobicity of the coating. The coatings reduced several fold the rate of Mg corrosion based on the H 2 evolution and other assessment methods, and effectively prevented the initial corrosion burst over the first 24 h. In vitro tissue culture studies demonstrated cytocompatibility of the coatings. These results reveal excellent anticorrosive properties and good cytocompatibility of the hybrid alkylsilane coatings and suggest great potential for use of these coatings on resorbable Mg devices.

Classical density functional theory (CDFT) is a useful theory in many fields. The basis of CDFT is spherical model and extending it to nonspherical molecules is a challenging issue due to the orientation/configuration of the molecules, which implies more complicated molecular models, and higher computational costs. In this work, we propose a dual-model classical density functional theory (DM-CDFT) to address this issue. The theory uses a more precise model (all-atom model) and a simpler model (coarsening model) to construct the external and excess free energy functionals, respectively. By using this methodology, CDFT could handle orientation/configuration effects with low computational costs. The theory is examined by applying it to gas adsorption (such as C 2 H 2 /C 2 H 4 /C 2 H 6 and toxic gases) in porous materials, and the predicted adsorption isotherms verify the accuracy of the theory. Additionally, the predicted density profile indicates that rotation entropy plays an important role in the adsorption of nonspherical molecules.