Significance: Patients suffering from ischemic strokes have limited therapeutic options and are often left with considerable disabilities. To promote neurological recovery, angiogenesis has been proposed as a promising therapeutic target. So far, experimental efforts to enhance vessel growth have almost exclusively focused on vascular growth factor supplementation; this approach has been shown not to be clinically viable due to hemorrhagic risks. Here, we pursued an alternative approach by targeting the guidance molecule Nogo-A, which has been recently shown to inhibit developmental central nervous system angiogenesis. Blockage of the Nogo-A pathway results in restoration of a mature vascular bed within the periinfarct zone. Moreover, we observe enhanced recovery-associated tissue responses and regain of motor functions that strongly correlate with vascular growth.

The blood–brain barrier (BBB) is a specialized vascular structure that protects the brain micro-environment from toxins and pathogens in the blood. At the same time, the BBB presents a significant challenge for drug development, as it restricts the entry of most therapeutics into the brain. In this review, we first examine recent findings on the molecular and cellular architecture of the BBB, emphasizing the diverse mechanisms that facilitate the transport and exchange of molecules between the blood and the brain. We discuss current knowledge on the heterogeneity of the BBB along the arteriovenous axis and across different brain regions. Then, we explore the molecular and functional changes in the BBB that occur during normal ageing, neurodegeneration and acute brain injuries, and how prolonged BBB impairment affects transport mechanisms and disease progression. Additionally, we discuss novel developments in drug delivery strategies to transport small molecules, biologicals or cellular therapeutics across the BBB. Finally, we examine therapeutic opportunities to restore the BBB and discuss future directions in the field.

Injuries to the CNS lead to severe and often irreversible deficits in sensorimotor and autonomous function. In spinal cord injury (SCI), mechanical damage results in the death of local neurons and glia at the lesion site within minutes to hours. This is followed by a delayed secondary damage phase

Background: Stroke research heavily relies on rodent behavior when assessing underlying disease mechanisms and treatment efficacy. Although functional motor recovery is considered the primary targeted outcome, tests in rodents are still poorly reproducible and often unsuitable for unraveling the complex behavior after injury. Results: Here, we provide a comprehensive 3D gait analysis of mice after focal cerebral ischemia based on the new deep learning-based software (DeepLabCut, DLC) that only requires basic behavioral equipment. We demonstrate a high precision 3D tracking of 10 body parts (including all relevant joints and reference landmarks) in several mouse strains. Building on this rigor motion tracking, a comprehensive post-analysis (with >100 parameters) unveils biologically relevant differences in locomotor profiles after a stroke over a time course of 3 weeks. We further refine the widely used ladder rung test using deep learning and compare its performance to human annotators. The generated DLC-assisted tests were then benchmarked to five widely used conventional behavioral set-ups (neurological scoring, rotarod, ladder rung walk, cylinder test, and single-pellet grasping) regarding sensitivity, accuracy, time use, and costs. Conclusions: We conclude that deep learning-based motion tracking with comprehensive post-analysis provides accurate and sensitive data to describe the complex recovery of rodents following a stroke. The experimental set-up and analysis can also benefit a range of other neurological injuries that affect locomotion.

The mouse retina provides an excellent model for studying angiogenesis. Recent advancements in high-throughput microscopy and image analysis provide great tools to visualize and describe the complexity of the retinal vascular architecture in a detailed and comprehensive way. Most developmental studies have focused on only a few parameters mostly in the inner-most layers that do not describe the entirety of the three-dimensional vascular network. Here, we analyzed the entire three-dimensional retinal vascular architecture and its growth and remodeling starting from the age of postnatal day 3 to 4 months in mice. We show plexus specific characteristics of the vasculature in terms of vascular tissue fraction, branching and length of the blood vessels, and distance and distribution between single capillaries. Such detailed knowledge is of particular interest, as it has become apparent that disease-specific mechanisms and treatments affect the retinal vasculature often in a plexus specific way.