Brainstem Surgery: Functional Surgical Anatomy with the Use of an Advanced Modern Intraoperative Neurophysiological Procedure.

Intraoperative neurophysiology (ION) in brainstem surgery evolved as brainstem surgery advanced.The original idea of brainstem mapping (BSM) is a neurophysiological procedure to locate cranial nerve motor nuclei (CNMN) on the floor of the fourth ventricle. With the introduction of various skull base approaches to the brainstem, BSM is carried out on any surface of the brainstem to expose the safe entry zone to the intrinsic brainstem lesion. It is the modern concept of BSM, a broader definition of BSM. BSM enables to avoid direct damage to the CNMN when approaching the brainstem through the negative mapping region.The corticobulbar tract (CBT) motor evoked potential (MEP) is another ION procedure in brainstem surgery. It enables monitoring of the functional integrity of the whole cranial motor pathway without interrupting surgical procedures. Combined application of both BSM and CBT-MEP monitoring is indispensable for the functional preservation of the CNMN and their supranuclear innervation during the brainstem surgery.In this paper, the neurophysiological aspect of BSM and the CBT-MEP was fully described. Normal anatomical background of the floor of the fourth ventricle and the detail of the CBT anatomy were demonstrated to better understand their clinical usefulness, limitations, and surgical implications derived from ION procedures. Finally, a future perspective in the role of ION procedures in brainstem surgery was presented. The latest magnetic resonance imaging (MRI) technology can allow surgeons to find an "on the image" safe entry zone to the brainstem. However, the role of BSM and the CBT-MEP monitoring in terms of safe brainstem surgery stays unshakable. Special attention was paid for the recent trend of management in diffuse intrinsic pontine gliomas. A new role of BSM during a stereotactic biopsy was discussed.It is the authors' expectation that the paper enhances the clinical application of a contemporary standard of the ION in brainstem surgery and supports safer brainstem surgery more than ever and in the future.

Diazoxide blocks or reduces microgliosis when applied prior or subsequent to motor neuron injury in mice.

Diazoxide (DZX), an anti-hypertonic and anti-hypoglycemic drug, was shown to have anti-inflammatory effects in several injured cell types outside the central nervous system. In the brain, the neuroprotective potential of DZX is well described, however, its anticipated anti-inflammatory effect after acute injury has not been systematically analyzed. To disclose the anti-inflammatory effect of DZX in the central nervous system, an injury was induced in the hypoglossal and facial nuclei and in the oculomotor nucleus by unilateral axonal transection and unilateral target deprivation (enucleation), respectively. On the fourth day after surgery, microglial analysis was performed on tissue in which microglia were DAB-labeled and motoneurons were labeled with immunofluorescence. DZX treatment was given either prophylactically, starting 7 days prior to the injury and continuing until the animals were sacrificed, or postoperatively only, with daily intraperitoneal injections (1.25 mg/kg; in 10 mg/ml dimethyl sulfoxide in distilled water). Prophylactically + postoperatively applied DZX completely eliminated the microglial reaction in each motor nuclei. If DZX was applied only postoperatively, some microglial activation could be detected, but its magnitude was still significantly smaller than the non-DZX-treated controls. The effect of DZX could also be demonstrated through an extended period, as tested in the hypoglossal nucleus on day 7 after the operation. Neuronal counts, determined at day 4 after the operation in the hypoglossal nucleus, demonstrated no loss of motor neurons, however, an increased Feret's diameter of mitochondria could be measured, suggesting increased oxidative stress in the injured cells. The increase of mitochondrial Feret's diameter could also be prevented with DZX treatment.

Hindbrain neurovascular anatomy of adult goldfish (Carassius auratus).

The goldfish hindbrain develops from a segmented (rhombomeric) neuroepithelial scaffold, similar to other vertebrates. Motor, reticular and other neuronal groups develop in specific segmental locations within this rhombomeric framework. Teleosts are unique in possessing a segmental series of unpaired, midline central arteries that extend from the basilar artery and penetrate the pial midline of each hindbrain rhombomere (r). This study demonstrates that the rhombencephalic arterial supply of the brainstem forms in relation to the neural segments they supply. Midline central arteries penetrate the pial floor plate and branch within the neuroepithelium near the ventricular surface to form vascular trees that extend back towards the pial surface. This intramural branching pattern has not been described in any other vertebrate, with blood flow in a ventriculo-pial direction, vastly different than the pial-ventricular blood flow observed in most other vertebrates. Each central arterial stem penetrates the pial midline and ascends through the floor plate, giving off short transverse paramedian branches that extend a short distance into the adjoining basal plate to supply ventromedial areas of the brainstem, including direct supply of reticulospinal neurons. Robust r3 and r8 central arteries are significantly larger and form a more interconnected network than any of the remaining hindbrain vascular stems. The r3 arterial stem has extensive vascular branching, including specific vessels that supply the cerebellum, trigeminal motor nucleus located in r2/3 and facial motoneurons found in r6/7. Results suggest that some blood vessels may be predetermined to supply specific neuronal populations, even traveling outside of their original neurovascular territories in order to supply migrated neurons.

Adult islet1 Expression Outlines Ventralized Derivatives Along Zebrafish Neuraxis.

Signals issued by dorsal roof and ventral floor plates, respectively, underlie the major patterning process of dorsalization and ventralization during vertebrate neural tube development. The ventrally produced morphogen Sonic hedgehog (SHH) is crucial for vertebrate hindbrain and spinal motor neuron development. One diagnostic gene for motor neurons is the LIM/homeodomain gene islet1, which has additional ventral expression domains extending into mid- and forebrain. In order to corroborate motor neuron development and, in particular, to improve on the identification of poorly documented zebrafish forebrain islet1 populations, we studied adult brains of transgenic islet1-GFP zebrafish (3 and 6 months). This molecular neuroanatomical analysis was supported by immunostaining these brains for tyrosine hydroxylase (TH) or choline acetyltransferase (ChAT), respectively, revealing zebrafish catecholaminergic and cholinergic neurons. The present analysis of ChAT and islet1-GFP label confirms ongoing adult expression of islet1 in zebrafish (basal plate) midbrain, hindbrain, and spinal motor neurons. In contrast, non-motor cholinergic systems lack islet1 expression. Additional presumed basal plate islet1 positive systems are described in detail, aided by TH staining which is particularly informative in the diencephalon. Finally, alar plate zebrafish forebrain systems with islet1 expression are described (i.e., thalamus, preoptic region, and subpallium). We conclude that adult zebrafish continue to express islet1 in the same brain systems as in the larva. Further, pending functional confirmation we hypothesize that the larval expression of sonic hedgehog (shh) might causally underlie much of adult islet1 expression because it explains findings beyond ventrally located systems, for example regarding shh expression in the zona limitans intrathalamica and correlated islet1-GFP expression in the thalamus.

Development and Functional Organization of the Cranial Nerves in Lampreys.

Lampreys, together with hagfishes, are the only extant representatives of the oldest branch of vertebrates, the agnathans, which are the sister group of gnathostomes; therefore, studies on these animals are of great evolutionary significance. Lampreys exhibit a particular life cycle with remarkable changes in their behavior, concomitant, in part, with important modifications in the head and its musculature, which might influence the development of the cranial nerves. In this context, some cranial nerves such as the optic nerve and the ocular motor nerves, which develop slowly during an extremely long larval period lasting more than five years, have been more thoroughly investigated; however, much less experimental information is available about others, such as the facial or the hypoglossal nerves. In addition, the possible existence of a "true" accessory nerve in these animals is still a matter of conjecture. Although growing in last decades, investigations on the physiology of the lamprey cranial nerves is scanty. This review focuses on past and recent findings that have contributed to characterize the anatomical organization of the cranial nerves in lampreys, including their components and nuclei, and their relations in the brain; in addition, comments on their development and functional role are also included. Anat Rec, 302:512-539, 2019. © 2018 Wiley Periodicals, Inc.

An exercise in brain genoarchitectonics: Analysis of AZIN2-Lacz expressing neuronal populations in the mouse hindbrain.

We examined in detail the distribution of AZIN2 (antizyme inhibitor 2) expression in the adult mouse hindbrain and neighboring spinal cord. AZIN2, similar to previously known AZIN1, is a recently-discovered, a functional paralog of ornithine decarboxylase (ODC). Due to their structural similarity to ODC, both AZIN1 and AZIN2 counteract the inhibitory action of 3 known antizymes (AZ1-3) on the ODC synthesis of polyamines, thus increasing intracytoplasmic levels of polyamines. AZIN2 is strongly, but heterogeneously, expressed in the brain. Our study uses a mouse line carrying an AZIN2-LacZ construct, and, in our topographic analysis of AZIN2-positive structures, we intend to share new knowledge about the rhombomeric segmentation of the hindbrain (a function of Hox paralogs and other genes). The observed labeled cell populations predominantly coincide with known cholinergic and glutamatergic cells, but occasionally also correspond to GABAergic, and possibly glycinergic cells. Some imperfectly known hindbrain populations stood out in unprecedented detail, and some axonal tracts were also differentially stained. © 2017 Wiley Periodicals, Inc.

Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain.

Cell adhesion molecule cadherins play important roles in both development and maintenance of adult structures. Most studies on cadherin expression have been carried out in developing organisms, but information on cadherin distribution in adult vertebrate brains is limited. In this study we used in situ hybridization to examine mRNA expression of three cadherins, protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain. Each cadherin exhibits a distinct expression pattern in the fish brain, with protocadherin-19 and protocadherin-17 showing much wider and stronger expression than that of cadherin-6. Both protocadherin-19 and protocadherin-17-expressing cells occur throughout the brain, with strong expression in the ventromedial telencephalon, periventricular regions of the thalamus and anterior hypothalamus, stratum periventriculare of the optic tectum, dorsal tegmental nucleus, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. Numerous sensory structures (e.g., auditory, gustatory, lateral line, olfactory, and visual nuclei) and motor nuclei (e.g., oculomotor, trochlear, trigeminal motor, abducens, and vagal motor nuclei) contain protocadherin-19 and/or protocadherin-17-expressing cell. Expression of these two protocadherins is similar in the ventromedial telencephalon, thalamus, hypothalamus, facial, and vagal lobes, but substantially different in the dorsolateral telencephalon, intermediate layers of the optic tectum, and cerebellar valvula. In contrast to the two protocadherins, cadherin-6 expression is much weaker and limited in the adult fish brain.

Roles of the orexin system in central motor control.

The neuropeptides orexin-A and orexin-B are produced by one group of neurons located in the lateral hypothalamic/perifornical area. However, the orexins are widely released in entire brain including various central motor control structures. Especially, the loss of orexins has been demonstrated to associate with several motor deficits. Here, we first summarize the present knowledge that describes the anatomical and morphological connections between the orexin system and various central motor control structures. In the next section, the direct influence of orexins on related central motor control structures is reviewed at molecular, cellular, circuitry, and motor activity levels. After the summarization, the characteristic and functional relevance of the orexin system's direct influence on central motor control function are demonstrated and discussed. We also propose a hypothesis as to how the orexin system orchestrates central motor control in a homeostatic regulation manner. Besides, the importance of the orexin system's phasic modulation on related central motor control structures is highlighted in this regulation manner. Finally, a scheme combining the homeostatic regulation of orexin system on central motor control and its effects on other brain functions is presented to discuss the role of orexin system beyond the pure motor activity level, but at the complex behavioral level.

Development of the human oculomotor nuclear complex: somatic nuclei.

BACKGROUND: Precise anatomical data on the development of human oculomotor somatic nuclei (OSN) remain rare. DESIGN/SUBJECTS: This study describes the histology of human OSN in 11 preterm and full-term infants aged 20-43 postmenstrual weeks who died of various causes. Celloidin-embedded serial sections were stained with the Klüver-Barrera and other conventional methods including silver impregnation. To evaluate the growth of OSN quantitatively, the author estimated the nuclear volume and the average neuronal area on morphometry. RESULTS: Four subnuclei were identified at 20-21 weeks: the fascicular, principal, dorsal median, and ventral median nucleus. Early tigroid Nissl bodies appeared in presumed motoneurons by 27-28 weeks, then resembled adult Nissl bodies at birth. On silver impregnation, the oculomotor nerve roots, crossed or uncrossed fibers at the midline, and a plexus of efferent or afferent axons in the neuropil were observed at 20-21 weeks. Then, the plexus was elaborated to form a perineuronal net of thin axon terminals by 28-29 weeks. The nuclear volume of OSN exponentially increased with age over 20-43 weeks, while the average of neuronal profile areas linearly increased in each subnucleus; the coefficient of regression was largest in the principal nucleus, and the regression lines nearly overlapped among the other subnuclei. Statistical analysis confirmed that the average neuronal area was largest in the principal nucleus in older cases. CONCLUSION: This study suggests that four subnuclei can be distinguished in human OSN by mid gestation, and that the principal nucleus may be different in neuronal cytoarchitecture from the others.

A hindbrain segmental scaffold specifying neuronal location in the adult goldfish, Carassius auratus.

The vertebrate hindbrain develops as a series of well-defined neuroepithelial segments or rhombomeres. While rhombomeres are visible in all vertebrate embryos, generally there is not any visible segmental anatomy in the brains of adults. Teleost fish are exceptional in retaining a rhombomeric pattern of reticulospinal neurons through embryonic, larval, and adult periods. We use this feature to map more precisely the segmental imprint in the reticular and motor basal hindbrain of adult goldfish. Analysis of serial sections cut in three planes and computer reconstructions of retrogradely labeled reticulospinal neurons yielded a segmental framework compatible with previous reports and more amenable to correlation with surrounding neuronal features. Cranial nerve motoneurons and octavolateral efferent neurons were aligned to the reticulospinal scaffold by mapping neurons immunopositive for choline acetyltransferase or retrogradely labeled from cranial nerve roots. The mapping corresponded well with the known ontogeny of these neurons and helps confirm the segmental territories defined by reticulospinal anatomy. Because both the reticulospinal and the motoneuronal segmental patterns persist in the hindbrain of adult goldfish, we hypothesize that a permanent "hindbrain framework" may be a general property that is retained in adult vertebrates. The establishment of a relationship between individual segments and neuronal phenotypes provides a convenient method for future studies that combine form, physiology, and function in adult vertebrates.