Undulating course of nerve fibres and bands of Fontana in peripheral nerves of the rat

Summary The undulating course of nerve fibres and the optical effect of that course, i.e. the bands of Fontana, were studied in the peripheral nerves of the adult rat using light microscopy. The arrangement of collagen fibres in the endoneurium of these nerves was evaluated using transmission and scanning electron microscopy. No nerve fibres undulation was noted on the intracranial sections of the cranial nerves or on the spinal roots. In their endoneurium a few, irregularly arranged collagen fibrils were found. In contrast, the nerve fibres undulation and Fontana's bands were a constant feature in the peripheral course of the nerve trunks. They were discernible in vivo and on excised unfixed as well as fixed nerves. The nerve fibres follow a sine-curve course of variable frequence and amplitude. Exposed in vivo, the nerve fibres retained their wave-like course even after removal of the epineurium and perineurium. The endoneurium of these nerves contained numerous undulating longitudinally oriented bundles of collagen fibrils. These findings suggest that the undulating course of the nerve fibres in peripheral nerves is conditional upon the quantity and arrangement of their endoneurial collagen fibrils. When the nerve was stretched in the course of movement, the undulation became straightened out until it disappeared. Conversely, nerve shortening enhanced the undulation. Thus the wave-like alignment of the nerve fibres represents a physiological reserve length for nerve stretching.     

Three‐Dimensional Visualization of Developing Neurovascular Architecture in the Craniofacial Region of Embryonic Mice

Recent studies have highlighted the mechanism of vascular and axonal guidance to ensure proper morphogenesis and organogenesis. We aimed to perform global mapping of developing neurovascular networks during craniofacial development of embryonic mice. To this end, we developed histology‐based three‐dimensional (3D) reconstructions using paraffin‐embedded serial sections obtained from mouse embryos. All serial sections were dual‐immunolabeled with Pecam1 and Pgp9.5/Gap43 cocktail antibodies. All immunolabeled serial sections were digitized with virtual microscopy to acquire high spatial resolution images. The 3D reconstructs warranted superior positional accuracy to trace the long‐range connectivity of blood vessels and individual cranial nerve axons. It was feasible to depict simultaneously the details of angiogenic sprouting and axon terminal arborization and to assess quantitatively the locoregional proximity between blood vessels and cranial nerve axons. Notably, 3D views of the craniofacial region revealed the following: Branchial arch arteries and blood capillary plexi were formed without accompanying nerves at embryonic day (E) 9.5. Cranial nerve axons began to grow into the branchial arches, developing a labyrinth of small blood vessels at E10.5. Vascular remodeling occurred, and axon terminals of the maxillary, mandibular, chorda tympani, and hypoglossal nerve axons had arborized around the lateral lingual swellings at E11.5. The diverged patterning of trigeminal nerves and the arterial branches from the carotid artery became congruent at E11.5. The overall results support the advantage of dual‐immunolabeling and 3D reconstruction technology to document the architecture and wiring of the developing neurovascular networks in mouse embryos. Anat Rec, 298:1824–1835, 2015. © 2015 Wiley Periodicals, Inc.     

Cerebral arterial stenoses and stroke: novel features of Aicardi‐Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression

Aicardi‐Goutières syndrome (AGS) is a rare inborn multisystemic disease, resembling intrauterine viral infection and resulting in psychomotor retardation, spasticity and chilblain‐like skin lesions. Diagnostic criteria include intracerebral calcifications and elevated interferon‐alpha and pterin levels in cerebrospinal fluid (CSF). We report on four adult siblings with unknown neurodegenerative disease presenting with cerebrovascular stenoses, stroke and glaucoma in childhood, two of whom died at the age of 40 and 29 years. Genome‐wide homozygosity mapping identified 170 candidate genes embedded in a common haplotype of 8Mb on chromosome 20q11‐13. Next generation sequencing of the entire region identified the c.490C>T (p.Arg164X) mutation in SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings. Clinical diagnosis of AGS was then confirmed by demonstrating intracerebral calcifications on cranial computed tomography in all siblings and elevated pterin levels in CSF in three of them. In patient fibroblasts, lack of SAMHD1 protein expression was associated with increased basal expression of IL8, while stimulated expression of IFNB1 was reduced. We conclude that cerebrovascular stenoses and stroke associated with the Arg164X mutation in SAMHD1 extend the phenotypic spectrum of AGS. The observed vascular changes most likely reflect a vasculitis caused by dysregulated inflammatory stress response. © 2010 Wiley‐Liss, Inc.