A Hairy End to a Chilling Event.

In the skin, sympathetic nerves, arrector pili muscles, and hair follicles form a tri-lineage unit to cause piloerection or goosebumps. In this issue of Cell, Schwartz et al. report that, beyond goosebumps, muscle-anchored nerves form "synapse-like" connections with hair follicle stem cells to promote hair regeneration in response to cold.

Extensive Connections of the Canine Olfactory Pathway Revealed by Tractography and Dissection.

The olfactory sense of the domestic dog is widely recognized as being highly sensitive with a diverse function; however, little is known about the structure of its olfactory system. This study examined a cohort of mixed-sex mesaticephalic canines and used diffusion tensor imaging (DTI), an MRI technique, to map connections from the olfactory bulb to other cortical regions of the brain. The results were validated using the Klingler dissection method. An extensive pathway composed of five white matter tracts connecting to the occipital lobe, cortical spinal tract, limbic system, piriform lobe, and entorhinal pathway was identified. This is the first documentation of a direct connection between the olfactory bulb and occipital lobe in any species and is a step toward further understanding how the dog integrates olfactory stimuli into their cognitive function.SIGNIFICANCE STATEMENT The highly sensitive olfactory system of the domestic dog is largely unexplored. We applied diffusion tractography and dissection techniques to evaluate the white matter connections associated with the olfactory system in a large cohort of dogs. We discovered an extensive white matter network extending from the olfactory bulb to form novel connections directly to other cortices of the brain. This is the first documentation of these novel olfactory connections and provides new insight into how dogs integrate olfactory stimuli in their cognitive functioning.

Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice.

Neuropeptide Y (NPY) is best known for its effects in the brain as an orexigenic and anxiolytic agent and in reducing energy expenditure. NPY is also co-expressed with norepinephrine (NE) in sympathetic neurons. Although NPY is generally considered to modulate noradrenergic responses, its specific roles in autonomic physiology remain under-appreciated. Here, we show that sympathetic-derived NPY is essential for metabolic and cardiovascular regulation in mice. NPY and NE are co-expressed in 90% of prevertebral sympathetic neurons and only 43% of paravertebral neurons. NPY-expressing neurons primarily innervate blood vessels in peripheral organs. Sympathetic-specific NPY deletion elicits pronounced metabolic and cardiovascular defects in mice, including reductions in insulin secretion, glucose tolerance, cold tolerance, and pupil size and elevated heart rate, while notably, however, basal blood pressure was unchanged. These findings provide insight into target tissue-specific functions of NPY derived from sympathetic neurons and imply its potential involvement in metabolic and cardiovascular diseases.

Signaling - transcription interactions in mouse retinal ganglion cells early axon pathfinding -a literature review.

Sending an axon out of the eye and into the target brain nuclei is the defining feature of retinal ganglion cells (RGCs). The literature on RGC axon pathfinding is vast, but it focuses mostly on decision making events such as midline crossing at the optic chiasm or retinotopic mapping at the target nuclei. In comparison, the exit of RGC axons out of the eye is much less explored. The first checkpoint on the RGC axons' path is the optic cup - optic stalk junction (OC-OS). OC-OS development and the exit of the RGC pioneer axons out of the eye are coordinated spatially and temporally. By the time the optic nerve head domain is specified, the optic fissure margins are in contact and the fusion process is ongoing, the first RGCs are born in its proximity and send pioneer axons in the optic stalk. RGC differentiation continues in centrifugal waves. Later born RGC axons fasciculate with the more mature axons. Growth cones at the end of the axons respond to guidance cues to adopt a centripetal direction, maintain nerve fiber layer restriction and to leave the optic cup. Although there is extensive information on OC-OS development, we still have important unanswered questions regarding its contribution to the exit of the RGC axons out of the eye. We are still to distinguish the morphogens of the OC-OS from the axon guidance molecules which are expressed in the same place at the same time. The early RGC transcription programs responsible for axon emergence and pathfinding are also unknown. This review summarizes the molecular mechanisms for early RGC axon guidance by contextualizing mouse knock-out studies on OC-OS development with the recent transcriptomic studies on developing RGCs in an attempt to contribute to the understanding of human optic nerve developmental anomalies. The published data summarized here suggests that the developing optic nerve head provides a physical channel (the closing optic fissure) as well as molecular guidance cues for the pioneer RGC axons to exit the eye.

Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice.

Neuropeptide Y (NPY) is best known for its effects in the brain as an orexigenic and anxiolytic agent and in reducing energy expenditure. NPY is also co-expressed with Norepinephrine (NE) in sympathetic neurons. Although NPY is generally considered to modulate noradrenergic responses, its specific roles in autonomic physiology remain under-appreciated. Here, we show that sympathetic-derived NPY is essential for metabolic and cardiovascular regulation in mice. NPY and NE are co-expressed in 90% of prevertebral sympathetic neurons and only 43% of paravertebral neurons. NPY-expressing neurons primarily innervate blood vessels in peripheral organs. Sympathetic-specific deletion of NPY elicits pronounced metabolic and cardiovascular defects in mice, including reductions in insulin secretion, glucose tolerance, cold tolerance, pupil size, and an elevation in heart rate, while notably, however, basal blood pressure was unchanged. These findings provide new knowledge about target tissue-specific functions of NPY derived from sympathetic neurons and imply its potential involvement in metabolic and cardiovascular diseases.

White matter changes in fetal brains with ventriculomegaly.

Introduction: Ventriculomegaly (VM) is a fetal brain malformation which may present independently (isolated form) or in association with different cerebral malformations, genetic syndromes or other pathologies (non-isolated form). Methods: This paper aims to study the effect of ventriculomegaly on the internal tridimensional architecture of fetal brains by way of Klingler's dissection. Ventriculomegaly was diagnosed using fetal ultrasonography during pregnancy and subsequently confirmed by necropsy. Taking into consideration the diameter of the lateral ventricle (measured at the level of the atrium), the brains were divided into two groups: moderate ventriculomegaly (with atrial diameter between 13 and 15 mm) and severe ventriculomegaly (with atrial diameter above 15 mm). Results and discussion: The results of each dissection were described and illustrated, then compared with age-matched reference brains. In the pathological brains, fascicles in direct contact with the enlarged ventricles were found to be thinner and displaced inferiorly, the opening of the uncinate fasciculus was wider, the fornix was no longer in contact with the corpus callosum and the convexity of the corpus callosum was inverted. We have studied the prevalence of neurodevelopmental delay in children born with ventriculomegaly in the literature and discovered that a normal developmental outcome was found in over 90% of the mild VM cases, approximately 75% of the moderate and 60% in severe VM, with the correlated neurological impairments ranging from attention deficits to psychiatric disorders.

Stereotaxic Diffusion Tensor Imaging White Matter Atlas for the in vivo Domestic Feline Brain.

The cat brain is a useful model for neuroscientific research and with the increasing use of advanced neuroimaging techniques there is a need for an open-source stereotaxic white matter brain atlas to accompany the cortical gray matter atlas, currently available. A stereotaxic white matter atlas would facilitate anatomic registration and segmentation of the white matter to aid in lesion localization or standardized regional analysis of specific regions of the white matter. In this article, we document the creation of a stereotaxic feline white matter atlas from diffusion tensor imaging (DTI) data obtained from a population of eight mesaticephalic felines. Deterministic tractography reconstructions were performed to create tract priors for the major white matter projections of Corpus callosum (CC), fornix, cingulum, uncinate, Corona Radiata (CR), Corticospinal tract (CST), inferior longitudinal fasciculus (ILF), Superior Longitudinal Fasciculus (SLF), and the cerebellar tracts. T1-weighted, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) population maps were generated. The volume, mean tract length and mean FA, MD, AD and RD values for each tract prior were documented. A structural connectome was then created using previously published cortical priors and the connectivity metrics for all cortical regions documented. The provided white matter atlas, diffusivity maps, tract priors and connectome will be a valuable resource for anatomical, pathological and translational neuroimaging research in the feline model. Multi-atlas population maps and segmentation priors are available at Cornell's digital repository: https://ecommons.cornell.edu/handle/1813/58775.2.

White Matter Dissection of the Fetal Brain.

Neuroplasticity is a complex process of structural and functional reorganization of brain tissue. In the fetal period, neuroplasticity plays an important role in the emergence and development of white matter tracts. Here, we aimed to study the architecture of normal fetal brains by way of Klingler's dissection. Ten normal brains were collected from in utero deceased fetuses aged between 13 and 35 gestational weeks (GW). During this period, we observed modifications in volume, shape, and sulci configuration. Our findings indicate that the major white matter tracts follow four waves of development. The first wave (13 GW) involves the corpus callosum, the fornix, the anterior commissure, and the uncinate fasciculus. In the second one (14 GW), the superior and inferior longitudinal fasciculi and the cingulum could be identified. The third wave (17 GW) concerns the internal capsule and in the fourth wave (20 GW) all the major tracts, including the inferior-occipital fasciculus, were depicted. Our results suggest an earlier development of the white matter tracts than estimated by DTI tractography studies. Correlating anatomical dissection with tractography data is of great interest for further research in the field of fetal brain mapping.

Intraorbital Penetrating and Retained Foreign Bodies - A Neurosurgical Case Series.

AIM: To present the particularities of the intraorbital foreign bodies from a neurosurgical perspective by summarizing the findings of a case series. MATERIAL AND METHODS: A retrospective study was conducted including a consecutive series of 30 patients with intraorbital foreign bodies treated between 1999 and 2017. Statistical analysis was performed in order to characterize the factors that influence the location of the foreign bodies and the clinical signs. RESULTS: The orbital trauma occurred mostly in working accidents. Multiple intraorbital foreign bodies were found in 23.3% of the patients. Metallic foreign bodies were seen in 66.6%, and 30% had wooden foreign bodies. Nonmetallic foreign bodies were significantly associated with displacement of the eyeball, palpebral oedema and upper lid ptosis. Posterior orbit location was associated with displacement of the eyeball and conjunctival hemorrhage. Intraconal location was associated with mydriasis and conjunctival hemorrhage. The posterior orbit was occupied by foreign bodies in 63% of the patients. The foreign bodies were in the extraconal compartment in 55.55% of the cases. Small foreign bodies tend to be retained in the anterior orbit while large ones tend to be retained in the posterior orbit. CONCLUSION: The diagnosis and management of intraorbital foreign bodies must be tailored according to their type and location and to the clinical aspect of the patient.

The Geometry of the Circle of Willis Anatomical Variants as a Potential Cerebrovascular Risk Factor.

AIM: To correlate the anatomical variants of the circle of Willis with their effects on the hemodynamic and geometrical parameters responsible for the pathogenesis of neurological diseases. MATERIAL AND METHODS: The circle of Willis and the proximal segments of the main arteries were dissected and measured on ten formalin-fixed human brains. The anatomical variants were systematized using descriptive statistics. The mathematical models for brain perfusion and wall shear stress were developed by optimally approximating resistance to flow, vascular conductance, and branching. RESULTS: Eighty percent of the brains presented asymmetries, especially in the posterior communicating (70%) and anterior cerebral (40%) arteries. The posterior circulation had more variations (65.21%). Nine hypoplastic vessels were found in 7 brains. Atypical origins were observed in eight specimens. According to the mathematical models, which integrated each anatomical change in the global circle of Willis anatomy, the circle of Willis' geometry could represent a risk factor for intracranial aneurysms and atherosclerosis, mostly when hypoplastic arteries are present, due to high resistance to flow and imbalanced bifurcation geometry. Accessory vessels are less associated with cerebrovascular risk. CONCLUSION: We described anatomical variants of both the anterior and posterior circulations and their specific effects on the hemodynamic balance of cerebral blood flow.

Anatomy of the Limbic White Matter Tracts as Revealed by Fiber Dissection and Tractography.

BACKGROUND: The limbic tracts are involved in crucial cerebral functions such as memory, emotion, and behavior. The complex architecture of the limbic circuit makes it harder to approach compared with other white matter networks. Our study aims to describe the 3-dimensional anatomy of the limbic white matter by the use of 2 complementary study methods, namely ex vivo fiber dissection and in vivo magnetic resonance imaging-based tractography. METHODS: Three fiber dissection protocols were performed using blunt wooden instruments and a surgical microscope on formalin-fixed brains prepared according to the Klingler method. Diffusion tensor imaging acquisitions were done with a 3-Tesla magnetic resonance scanner on patients with head and neck pathology that did not involve the brain. Fiber tracking was performed with manually selected regions of interest. RESULTS: Cingulum, fornix, the anterior thalamic peduncle, the accumbofrontal bundle, medial forebrain bundle, the uncinate fasciculus, the mammillothalamic tract, ansa peduncularis, and stria terminalis were dissected and fiber tracked. For each tract, location, configuration, segmentation, dimensions, dissection and tractography particularities, anatomical relations, and terminations are described. The limbic white matter tracts were systematized as 2 concentric rings around the thalamus. The inner ring is formed by fornix, mammillothalamic tract, ansa peduncularis, stria terminalis, accumbofrontal fasciculus, and medial forebrain bundle and anterior thalamic peduncle, and the outer ring is formed by the cingulum and uncinate fasciculus. CONCLUSIONS: This paper proposes a fiber-tracking protocol for the limbic tracts inspired and validated by fiber dissection findings that can be used routinely in the clinical practice.

Morphometric study of the human brainstem and its neurovascular relations.

AIM: The brainstem is a very complex segment of the central nervous system because it has a high density of nuclei and tracts with vital functional roles. This explains the considerable difficulty of surgery for lesions located in or around the brainstem. Our paper aims to provide a concise description of the external configuration, its internal correspondence and the neurovascular relations of the brainstem with morphometric data that can be useful in surgical planning. MATERIAL AND METHODS: The study was conducted on formalin fixed brainstem specimens, which were harvested with respect to the topographic anatomy. Macroscopic measurements were performed with a Vernier caliper. RESULTS: The anatomical structures on the ventral and dorsal aspects of the brainstem are described and illustrated schematically. Their dimensions are also graphically represented using the mean values. Serial axial sections through the brainstem demonstrate the internal correspondence of its external features. Then there are presented the apparent origins and the proximal diameters of the cranial nerves and the arteries of the posterior circulation as well as their anatomical relations. CONCLUSION: The external morphometry of the brainstem correlated with the position of the internal structures provides landmarks with aplicability in neurosurgery especially in the fields of intrinsic brainstem lesions, posterior fossa and fourth ventricle surgery.