Analysis of the developing proteome has been complicated by a lack of tools that can be easily employed to label and identify newly synthesized proteins within complex biological mixtures. Here, we demonstrate that the methionine analogs azidohomoalanine and homopropargylglycine can be globally incorporated into the proteome of mice through facile intraperitoneal injections. These analogs contain bio-orthogonal chemical handles to which fluorescent tags can be conjugated to identify newly synthesized proteins. We show these non-canonical amino acids are incorporated into various tissues in juvenile mice and in a concentration dependent manner. Furthermore, administration of these methionine analogs to pregnant dams during a critical stage of murine development, E10.5–12.5 when many tissues are assembling, does not overtly disrupt development as assessed by proteomic analysis and normal parturition and growth of pups. This successful demonstration that non-canonical amino acids can be directly administered in vivo will enable future studies that seek to characterize the murine proteome during growth, disease and repair.

Protein post-translational modifications (PTMs) serve to give proteins new cellular functions and can influence spatial distribution and enzymatic activity, greatly enriching the complexity of the proteome. Lipidation is a PTM that regulates protein stability, function, and subcellular localization. To complement advances in proteomic identification of lipidated proteins, we have developed a method to image the spatial distribution of proteins that have been co- and post-translationally modified via the addition of myristic acid (Myr) to the N terminus. In this work, we use a Myr analog, 12-azidododecanoic acid (12-ADA), to facilitate fluorescent detection of myristoylated proteins in vitro and in vivo. The azide moiety of 12-ADA does not react to natural biological chemistries, but is selectively reactive with alkyne functionalized fluorescent dyes. We find that the spatial distribution of myristoylated proteins varies dramatically between undifferentiated and differentiated muscle cells in vitro. Further, we demonstrate that our methodology can visualize the distribution of myristoylated proteins in zebrafish muscle in vivo. Selective protein labeling with noncanonical fatty acids, such as 12-ADA, can be used to determine the biological function of myristoylation and other lipid-based PTMs and can be extended to study deregulated protein lipidation in disease states.

Introduction: Migraine headache prevalence, etiology, and clinical presentations change from childhood to adulthood. Dural innervation plays a role in headache symptomatology, but the changes in innervation during development have not been fully explored in the literature. Methods: A narrative literature review on developmental innervation of cranial dura mater in the context of migraine headache. Results: Dural structures, nerve distributions, and pain attributed to migraine headache at varying stages of development are discussed herein with a focus on clinical findings and presentations.Conclusions: There are many differences in migraine presentation throughout development. Notably, the nervus spinosus and nervus tentorii may play a role in developmental differences in migraine headache presentations between children and adults.

Cerebral vasospasm is a well-known entity following aneurysmal subarachnoid hemorrhage. While it has been described in trauma, it has been much less studied. There have been no previous reports of cerebral vasospasm following spontaneous subdural hematoma or after subdural hematoma evacuation. In this case report, we present a 38-year-old otherwise healthy female who suffered an acute spontaneous subdural hematoma. After surgical evacuation of her hematoma, she developed neurologic decline. Computer tomography angiography demonstrated intracranial vasospasm. She was treated with blood pressure augmentation and nimodipine. She went on to make a full neurologic recovery. To our knowledge, this is the first reported case of cerebral vasospasm after acute spontaneous subdural hematoma or after subdural hematoma evacuation, and the patient recovered without sequelae. The promising outcome of this case may provide a framework for future similar cases. Neurosurgeons and intensivists should keep cerebral vasospasm in their differentials for patients who have neurologic decline after craniotomy for acute subdural hematoma and have an otherwise negative scan for new acute abnormality.

Background: Detailed and accurate understanding of intrinsic brainstem anatomy and the interrelationship between its internal tracts and nuclei and external landmarks is of paramount importance for safe and effective brainstem surgery. Using anatomical models can be an important step in sharpening such understanding.Objective: To show the applicability of our developed virtual 3D model in depicting the safe entry zones (SEZs) to the brainstem.Methods: Accurate 3D virtual models of brainstem elements were created using high-resolution magnetic resonance imaging and computed tomography to depict brainstem SEZs.Results: All the described SEZs to different aspects of the brainstem were successfully depicted using our 3D virtual models. Conclusions:The virtual models provide an immersive experience of brainstem anatomy, allowing users to understand the intricacies of the microdissection that is necessary to appropriately traverse the brainstem nuclei and tracts toward a particular target. The models provide an unparalleled learning environment for illustrating SEZs into the brainstem that can be used for training and research.