The seminal contributions of Benedict Stilling (1810-1879) to neuroanatomy.

Benedict Stilling (1810-1879), was a prolific, prominent, and ambitious anatomist, who performed works on the organization of the nervous system for many years. He made numerous observations on the anatomy of the nervous system in various animal species. Stilling contributed to the establishment of significant foundations in the anatomy of the spinal cord, brainstem, and cerebellum. Stilling paved the way for future researchers by describing the techniques he used in his diligent studies published in his published books. In his books, which include many drawings and cadaveric images, he revealed the relationships between the structures in the nervous system. He also made significant contributions to neuroanatomy terminology by coining terms in these books. At the same time, some nuclei in the anatomy of the nervous system were later named after him as an eponym by many researchers. Therefore, Stilling's neuroanatomical works, which are still important today, should be appreciated. This article aims to emphasize his pioneering work in neuroanatomy.

Microsurgical anatomy of safe entry zones on the ventrolateral brainstem: a morphometric study.

Surgery of the brainstem is challenging due to the complexity of the area with cranial nerve nuclei, reticular formation, and ascending and descending fibers. Safe entry zones are required to reach the intrinsic lesions of the brainstem. The aim of this study was to provide detailed measurements for anatomical landmark zones of the ventrolateral surface of the human brainstem related to previously described safe entry zones. In this study, 53 complete and 34 midsagittal brainstems were measured using a stainless caliper with an accuracy of 0.01 mm. The distance between the pontomesencephalic and bulbopontine sulci was measured as 26.94 mm. Basilar sulcus-lateral side of pons (origin of the fibers of the trigeminal nerve) distance was 17.23 mm, transverse length of the pyramid 5.42 mm, and vertical length of the pyramid 21.36 mm. Lateral mesencephalic sulcus was 12.73 mm, distance of the lateral mesencephalic sulcus to the oculomotor nerve 13.85 mm, and distance of trigeminal nerve to the upper tip of pyramid 17.58 mm. The transverse length for the inferior olive at midpoint and vertical length were measured as 5.21 mm and 14.77 mm, consequently. The thickness of the superior colliculus was 4.36 mm, and the inferior colliculus 5.06 mm; length of the tectum was 14.5 mm and interpeduncular fossa 11.26 mm. Profound anatomical knowledge and careful analysis of preoperative imaging are mandatory before surgery of the brainstem lesions. The results presented in this study will serve neurosurgeons operating in the brainstem region.

Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors.

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors-in-chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.

The Historical Evolution of Topographical Mapping and Nomenclature of the Lateral Cervical and Lateral Spinal Nuclei.

The intricate organization of nuclei within the dorsolateral funiculus of the spinal cord has long been an area of interest in the field of neuroanatomy. Numerous researchers have endeavored to determine the morphology, neurochemistry, connections, and physiology of the lateral cervical nucleus and lateral spinal nucleus throughout history. This manuscript charts the historical progression in the mapping, naming, and comprehension of the lateral cervical nucleus and lateral spinal nucleus across a variety of species, such as rats, mice, marmosets, rhesus monkeys, and humans. It synthesizes significant research spanning decades, which together shed light on the nuanced topography of these nuclei, starting from Theodor Ziehen's foundational work in 1903, through Molander's precise mappings, to the detailed contemporary mappings by modern scholars. Despite the wealth of research elucidating the mappings of these nuclei, there remains a need for further investigation into their roles and neurochemical characteristics.

Vertebral landmarks for the identification of spinal cord segments in the mouse.

Accurate identification of spinal cord segments in relation to vertebral landmarks is essential to surgery aimed at experimental spinal cord injury. We have analyzed a complete series of high-resolution magnetic resonance (MR) images from the mouse spine in order to delineate the boundaries of spinal cord segments in relation to vertebral landmarks. The resulting atlas can be used to plan experimental approaches that require the accurate identification of a target spinal cord segment.

Bror Rexed (1914-2002) and His Pioneer Works on Spinal Cord Cytoarchitecture.

Swedish neuroscientist Bror Anders Rexed lived between 1914 and 2002. He was a renowned neuroscientist and a politician who packed a lot into his 88-year life. Bror Rexed is best known for his works on the description of the cytoarchitectonic organization of the cat spinal cord. Rexed laminae as an eponym is a historical landmark for the spinal cord cytoarchitecture. Rexed's name (particularly his surname) has also been linked to the du-reform in Swedish. In this article, we focus on his works on the central and peripheral nervous systems and translational approaches for neurosurgery, as well as his influence on health policies in Sweden.

Cervical Vestibular Evoked Myogenic Potentials in Idiopathic Intracranial Hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) is raised intracranial pressure without any identifiable etiology. The inner ear structures are susceptible to cerebrospinal fluid (CSF) pressure changes because of connections between the CSF space and the labyrinth to explain the audiovestibular symptoms, such as pulsatile tinnitus or dizziness, reported in 50% to 60% of these patients. The aim of this study was to investigate the vestibular functions using cervical vestibular evoked myogenic potentials (cVEMPs) in IIH. METHODS: cVEMPs were recorded in 30 patients with IIH before lumbar puncture. Thirty healthy volunteers constituted the control group. The latencies of peaks p13 and n23 and peak-to-peak amplitude of p13-n23 were measured. RESULTS: Responses were gathered bilaterally from all healthy controls. In 30 patients with IIH, 49 responses could be gathered from 60 tests (81.7%). The potential was absent bilaterally in five and unilaterally in one patient. When recorded, the latency and amplitude values of the responses of the patients were not significantly different from the healthy controls (P > 0.005). A correlation between CSF pressure and response persistence could not be determined. CONCLUSIONS: cVEMPs are affected in patients with IIH and the main finding is the absence of the responses. Increased intracranial pressure causing sound transmission changes within the inner ear can affect the saccular afferents and may end up with absent responses on air-conducted cVEMP recordings. To comment on the correlation between the CSF pressure and cVEMP changes, successive cVEMP recordings with longitudinal CSF pressure monitoring seem necessary.

Effects of cyanocobalamin and its combination with morphine on neuropathic rats and the relationship between these effects and thrombospondin-4 expression.

BACKGROUND: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. METHODS: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. RESULTS: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. CONCLUSIONS: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone.

Human cremaster muscle and cremasteric reflex: A comprehensive review.

OBJECTIVE: Human research on the cremaster muscle (CM), cremasteric reflex (CMR) and genitofemoral nerve (GFN) and reports on their clinical applications using electrophysiological and histological techniques are rare. We aimed to present a detailed review of the human CM and CMR based on our earlier publications and relevant literature. METHODS: Electromyography (EMG) of the CM was recorded using disposable needle electrodes. CMR was obtained with tactile and/or electrical stimulation of the inner thigh. Transcranial magnetic stimulation (TMS) and magnetic stimulation of the upper lumbar roots were applied; GFN was stimulated using a surface electrode at the anterior superior iliac spine. RESULTS: CM striated fibers comprised multiple motor end plates. CM needle EMG results were similar to those of the limb muscles in chronic neurogenic disorders. TMS produced clear-cut evoked motor responses from CM. GFN motor conduction time to CM was absent or delayed in patients with inguinal hernia. EMG of CM was abnormal in 40% of patients with premature ejaculation. CONCLUSION: CM is different from other skeletal muscles both morphologically and physiologically. Intersegmental sacrolumbar reflexes are useful for evaluating ejaculatory dysfunction. SIGNIFICANCE: CM is an important muscle for testis thermoregulation and sexual reflexes. Neurophysiological techniques are available for physiological and clinical studies.

Dorsal Horn of Mouse Lumbar Spinal Cord Imaged with CLARITY.

The organization of the mouse spinal dorsal horn has been delineated in 2D for the six Rexed laminae in our publication Atlas of the Spinal Cord: Mouse, Rat, Rhesus, Marmoset, and Human. In the present study, the tissue clearing technique CLARITY was used to observe the cyto- and chemoarchitecture of the mouse spinal cord in 3D, using a variety of immunohistochemical markers. We confirm prior observations regarding the location of glycine and serotonin immunoreactivities. Novel observations include the demonstration of numerous calcitonin gene-related peptide (CGRP) perikarya, as well as CGRP fibers and terminals in all laminae of the dorsal horn. We also observed sparse choline acetyltransferase (ChAT) immunoreactivity in small perikarya and fibers and terminals in all dorsal horn laminae, while gamma aminobutyric acid (GABA) and glutamate decarboxylase-67 (GAD67) immunoreactivities were found only in small perikarya and fibers. Finally, numerous serotonergic fibers were observed in all laminae of the dorsal horn. In conclusion, CLARITY confirmed the 2D immunohistochemical properties of the spinal cord. Furthermore, we observed novel anatomical characteristics of the spinal cord and demonstrated that CLARITY can be used on spinal cord tissue to examine many proteins of interest.

Odor Enrichment Increases Hippocampal Neuron Numbers in Mouse.

The hippocampus and olfactory bulb incorporate new neurons migrating from neurogenic regions in the brain. Hippocampal atrophy is evident in numerous neurodegenerative disorders, and altered hippocampal neurogenesis is an early pathological event in Alzheimer's disease. We hypothesized that hippocampal neurogenesis is affected by olfactory stimuli through the neural pathway of olfaction-related memory. In this study, we exposed mice to novel pleasant odors for three weeks and then assessed the number of neurons, non-neuronal cells (mainly glia) and proliferating cells in the hippocampus and olfactory bulb, using the isotropic fractionator method. We found that the odor enrichment significantly increased the neuronal cell numbers in the hippocampus, and promoted cell proliferation and neurogenesis in the olfactory bulb. In contrast, the glial cell numbers remained unchanged in both of the regions. Our results suggest that exposure to novel odor stimuli promotes hippocampal neurogenesis and support the idea that enriched environments may delay the onset or slow down the progression of neurodegenerative disorders.

Topographic Classification of the Thalamus Surfaces Related to Microneurosurgery: A White Matter Fiber Microdissection Study.

OBJECTIVE: To describe the topographic anatomy of surgically accessible surfaces of the human thalamus as a guide to surgical exploration of this sensitive area. METHODS: Using the operating microscope, we applied the fiber microdissection technique to study 10 brain specimens. Step-by-step dissections in superior-inferior, medial-lateral, and posterior-anterior directions were conducted to expose the surfaces and nuclei of the thalamus and to investigate the relevant anatomic relationships and visible connections. RESULTS: There were 4 distinct free surfaces of the thalamus identified: lateral ventricle surface, velar surface, cisternal surface, and third ventricle surface. Each is described with reference to recognizable anatomic landmarks and to the underlying thalamic nuclei. The neural structures most commonly encountered during the surgical approach to each individual surface are highlighted and described. CONCLUSIONS: Observations from this study supplement current knowledge, advancing the capabilities to define the exact topographic location of thalamic lesions. This improved understanding of anatomy is valuable when designing the most appropriate and least traumatic surgical approach to thalamic lesions. These proposed surface divisions, based on recognizable anatomic landmarks, can provide more reliable surgical orientation.

Spinal cord projections to the cerebellum in the mouse.

The projections from the spinal cord to the cerebellar cortex were studied using retrograde neuronal tracers. Thus far, no study has shown the detailed topographic mapping of the projections from the spinal neuron clusters to the cerebellar cortex regions for experimental animals, and there are no studies for the mouse. Tracers Fluoro-Gold and cholera toxin B were injected into circumscribed regions of the cerebellar cortex, and retrogradely labeled spinal cord neurons were mapped throughout the spinal cord. Spinal projections to the cerebellar cortex were mainly from five neuronal columns--central cervical nucleus, dorsal nucleus, lumbar and sacral precerebellar nuclei, and lumbar border precerebellar cells--and from scattered neurons located in the deep dorsal horn and laminae 6-8. The spinocerebellar projections to the cortex were mainly to the vermis. All five precerebellar cell columns projected to both anterior and posterior parts of the cerebellar cortex. Results of this study provide an amendment to the known rostral and caudal boundaries of the precerebellar cell columns in the mouse. Scattered precerebellar neurons in the most caudal deep dorsal horn and laminae 6-8 projected exclusively to the anterior part of the cerebellar cortex. In this study, no labeled spinal neurons were found to project to the lobules 6 and 7 of the cerebellar vermis, the flocculus, and the paraflocculus. Spinocerebellar neurons were located bilaterally, but the majority of the projections were contralateral for the central cervical nucleus, and ipsilateral for the remaining spinal precerebellar neuronal clusters.

The spinal cord of the common marmoset (Callithrix jacchus).

The marmoset spinal cord possesses all the characteristic features of a typical mammalian spinal cord, but with some interesting variation in the levels of origin of the limb nerves. In our study Nissl and ChAT sections of the each segment of the spinal cord in two marmosets (Ma5 and Ma8), we found that the spinal cord can be functionally and anatomically divided into six regions: the prebrachial region (C1 to C3); the brachial region (C4 to C8) - segments supplying the upper limb; the post-brachial region (T1 to L1) - containing the sympathetic outflow, and supplying the hypaxial muscles of the body wall; the crural region (L2 to L5) - segments supplying the lower limb; the postcrural region (L6) - containing the parasympathetic outflow; and the caudal region (L7 to Co4) - supplying the tail. In the rat, mouse, and rhesus monkey, the prebrachial region consists of segments C1 to C4 (with the phrenic nucleus located at the C4 segment), and the brachial region extends from C5 to T1 inclusive. The prefixing of the upper limb outflow in these two marmosets mirrors the finding in the literature that a large C4 contribution to the brachial plexus is common in humans.

Musculotopic organization of the motor neurons supplying forelimb and shoulder girdle muscles in the mouse.

We identified the motor neurons (MNs) supplying the shoulder girdle and forelimb muscles in the C57BL/6J mouse spinal cord using Fluoro-Gold retrograde tracer injections. In spinal cord transverse sections from C2 to T2, we observed two MN columns (medial and lateral) both with ventral and dorsal subdivisions. The dorsolateral column consisted of the biceps brachii, forearm extensors, forearm flexors, and hand MNs, and the ventrolateral column consisted of the latissimus dorsi, trapezius, teres major, deltoid, and triceps MNs. The supraspinatus muscle MNs were located in the dorsomedial column, and pectoralis major and serratus anterior MNs were located in the ventromedial columns. MNs of the dorsolateral column innervated the biceps brachii in mid-C4 to mid-C7, forearm extensors in caudal C4 to mid-T1, forearm flexors in rostral C5 to mid-T1, and hand muscles in mid-C8 to mid-T2 segments. The MNs innervating the trapezius were located in mid-C2 to mid-C4, triceps brachii in mid-C6 to rostral T1, deltoid in rostral C4 to mid-C6, teres major in rostral C5 to mid-C8, and latissimus dorsi in mid-C5 to caudal C8. In addition, MNs innervating the supraspinatus were located from rostral C4 to caudal C8, pectoralis major in mid-C6 to mid-T2, and serratus anterior in rostral C5 to caudal C7/rostral C8 segments. While the musculotopic pattern of MN groups was very similar to that documented for other species, we found differences in the position and cranio-caudal extent of some MN pools compared with previous reports. The identification of mouse forelimb MNs can serve as an anatomical reference for studying degenerative MN diseases, spinal cord injury, and developmental gene expression.

Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord.

The spinal precerebellar nuclei: calcium binding proteins and gene expression profile in the mouse.

We have localized the spinocerebellar neuron groups in C57BL/6J mice by injecting the retrograde neuronal tracer Fluoro-Gold into the cerebellum and examined the distribution of SMI 32 and the calcium-binding proteins (CBPs), calbindin-D-28K (Cb), calretinin (Cr), and parvalbumin (Pv) in the spinal precerebellar nuclei. The spinal precerebellar neuron clusters identified were the dorsal nucleus, central cervical nucleus, lumbar border precerebellar nucleus, lumbar precerebellar nucleus, and sacral precerebellar nucleus. Some dispersed neurons in the deep dorsal horn and spinal laminae 6-8 also projected to the cerebellum. Cb, Cr, Pv, and SMI 32 were present in all major spinal precerebellar nuclei and Pv was the most commonly observed CBP. A number of genes expressed in hindbrain precerebellar nuclei are also expressed in spinal precerebellar groups, but there were some differences in gene expression profile between the different spinal precerebellar nuclei, pointing to functional diversity amongst them.

The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury.

AIMS: Although hyperbaric oxygen (HBO) treatment following spinal cord injury (SCI) have been studied in terms of neurological function and tissue histology, there is a limited number studies on spinal cord tissue enzyme levels. MAIN METHODS: The effect of HBO treatment in SCI was investigated by measuring superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), nitric oxide synthase (NOS) and nitric oxide (NO) activity in the injured tissue. SCI was induced by applying an aneurysm clip extradurally at the level of T9-T11 vertebrae. Preoperative HBO (preopHBO) treatment was applied for 5days and postoperative HBO (postopHBO) for 7days. KEY FINDINGS: In the preopHBO group, a significant decrease was observed in NOS and NO compared to the SCI group. There was a decrease in SOD, NOS and NO in the postopHBO group when compared to the SCI group. In the pre-postHBO group SOD, GPx, NOS and NO decreased significantly. There was a decrease in SOD in postopHBO compared to preopHBO. In the prepostopHBO, SOD decreased significantly compared to that in the preopHBO group. The prepostopHBO presented a significant decrease in GPx compared to postopHBO (p<0.05 for all parameters). No significant difference was observed for catalase for all groups. Significant improvement was found in BBB scores for both postopHBO and prepostHBO groups when compared to the SCI group (p<0.05). SIGNIFICANCE: HBO treatment was found to be beneficial following SCI in terms of biochemical parameters and functional recovery in the postoperative period.