Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified in central nervous system disorders. Membrane leakage and electrolyte imbalances, pro-apoptotic pathway activation, and mitophagy are among the mechanisms implicated in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as ischemic stroke. In this review, we summarize mitochondrial pathways that contribute to disease progression. Further, we discuss pathological states that damaged mitochondria impose on normal nervous system processes and explore new therapeutic approaches to mitochondrial diseases.

Retinal ganglion cells (RGCs) exhibit compartmentalized organization, receiving synaptic inputs through their dendrites and transmitting visual information from the retina to the brain through the optic nerve. Little is known about the structure of RGC axon bundles extending from individual RGC somas to the optic nerve head (ONH) and how they respond to disease insults. We recently introduced visible-light optical coherence tomography fibergraphy (vis-OCTF), a technique for directly visualizing and analyzing mouse RGC axon bundlesin vivo. In this study, we validated vis-OCTF's ability to quantify RGC axon bundles with an increased number of RGCs using mice deficient in BCL2-associated X protein (BAX^−/−). Next, we performed optic nerve crush (ONC) injury on wild-type (WT) mice and showed that the changes in RGC axon bundle width and thickness were location-dependent. Our work demonstrates the potential of vis-OCTF to longitudinally quantify and track RGC damage at single axon bundle level in optic neuropathies.SIGNIFICANCE STATEMENTNearly all clinical and preclinical studies measure the retinal nerve fiber (RNFL) thickness as the sole indicator of retinal ganglion cell (RGC) damage without investigating RGC axon bundles directly. We demonstrated visible-light optical coherence tomography fibergraphy (vis-OCTF) to directly quantify global and regional RGC axon bundle organizationsin vivoas a new biomarker for RGC health. We validatedin vivovis-OCTF measures using both confocal microscopy of the immunostained flat-mounted retina and numerical simulations. Vis-OCTF for monitoring RGC axon bundle organization has the potential to bring new insight into RGC damage in optic neuropathies.

Neuroanatomy laboratory training is crucial for the education of neurosurgery residents and medical students. Since the brain is a complex and three-dimensional structure, it is challenging to understand the anatomical relationship of the cortex, internal structures, arteries, and veins without appropriate adjuncts. Several injection agents—including the inks/dyes, latex, polyester, acrylic resins, phenol, polyethylene glycol, and phenoxyethanol—have been explored. Colored silicon injection protocols for the head and neck vessels’ perfusion have greatly aided the study of neuroanatomy and surgical planning. This report presents a colored silicone injection method in detail, and also highlights the technical shortcomings of the standard techniques and workarounds for common challenges during 35 human cadaveric head injections. The human cadaveric head preparation and the coloring of the head vessels are divided into decapitation, tissue fixation with 10% formalin, the placement of the Silastic tubing into the parent vessels, the cleaning of the vessels from clots, and the injection of the colored silicone into the vessels. We describe the technical details of the preparation, injection, and preservation of cadaveric heads, and outline common challenges during colored silicone injection, which include the dislocation of the Silastic tubing during the injection, the injection of the wrong or inappropriate colored silicone into the vessel, intracranial vessel perforation, the incomplete silicone casting of the vessel, and silicone leakage from small vessels in the neck. Solutions to these common challenges are provided. Ethyl alcohol fixed, colored human heads provided the long-term preservation of tissue, and improve the sample consistency and preservation for the teaching of neuroanatomy and surgical technique.

A Correction to this paper has been published: https://doi.org/10.1038/s41536-021-00125-3