Full: Ontogenesis and development of the nonhuman primate pulvinar.

Recent evidence demonstrates that the pulvinar nuclei play a critical role in shaping the connectivity and function of the multiple cortical areas they connect. Surprisingly, however, little is known about the development of this area, the largest corpus of the thalamic nuclei, which go on to occupy 40% of the adult thalamus in the human. It was proposed that the nonhuman primate and the human pulvinar develop according to very different processes, with a greatly reduced neurogenic period in nonhuman primate compared to human and divergent origins. In the marmoset monkey, we demonstrate that neurons populating the pulvinar are generated throughout gestation, suggesting that this aspect of development is more similar to the human than first predicted. While we were able to confirm the diencephalic source of pulvinar neurons, we provide new evidence contesting the presence of an additional niche in the telencephalon. Finally, our study defines new molecular markers that will simplify future investigations in the development and evolution of the pulvinar.

The third ventricle of the human fetal brain: Normative data and pathologic correlation. A 3D transvaginal neurosonography study.

OBJECTIVE: The objective of the study are to describe (a) the technical aspects and (b) the anatomical boundaries of the fetal third ventricle (3V) on the midsagittal sonographic view and to assess (c) different biometric parameters in normal and abnormal fetuses and (d) and their reproducibility. METHODS: This study included 67 normal and 50 CNS anomalies fetuses which include (1) obstructive severe ventriculomegaly (SVM; atrial width ≥ 15 mm), (2) moderate ventriculomegaly (10-14.9 mm), and (3) corpus callosum agenesis (ACC). All underwent transvaginal 3D neurosonography of the midsagittal view of the 3V. The following parameters were measured: area, perimeter, craniocaudal and anteroposterior (AP) diameters, interthalamic adhesion diameter (ITAD), wedge angle, and the ratio between the last 2 variables (ITAD/WA). Repeatability was also assessed. RESULTS: The ITAD and the ITAD/WA are significantly different between normal fetuses and the SVM (P ≤ .001). Interthalamic adhesion diameter of ≤7.1 mm is able to identify SVM with 98.6% accuracy (CI: 0.92-0.99). In ACC cases, the AP diameter is significantly shorter than both normal fetuses and ventriculomegaly. Intraobserver/interobserver reliability was good for most variables. CONCLUSIONS: Transvaginal neurosonography enables visualization of the normal and abnormal fetal third ventricle. An ITAD <7.1 identifies aqueductal stenosis as the likely etiology of severe ventriculomegaly with an accuracy of 98.6%.

Third Ventricular Cerebrospinal Fluid Cysts of Thalamic Origin: Review of Embryologic Origin, Presentation, and Management Strategies with a Case Series.

OBJECTIVE: Third ventricular cerebrospinal fluid (CSF) cysts of thalamic origin are rare. The objective of this study is to review their possible pathogenesis, clinical presentation, and management strategies with a case series describing management via an endoscopic approach with fenestration using a single burr-hole technique. METHODS: A systematic literature review of reported cases of thalamic cysts was conducted with further meta-analysis of CSF cysts that involve the third ventricle. The mode of presentation, pathologic analysis, surgical management, and outcomes were analyzed. RESULTS: Twenty-two studies reported between 1990 and 2013 described 42 cases of thalamic cyst. Of those cases, 13 were consistent with CSF cyst that originated in the thalamus and involved the third ventricle. Eight cases (61.5%) were treated via endoscopic fenestration, 2 cases (15.4%) were surgically drained, 2 cases (15.4%) were stereotactically aspirated, and 1 case (7.69%) was observed. The most common presenting symptoms were gait disturbance (26.3%) and headaches (26.3%) followed by tremors (15.8%) and weakness (15.8%). In our series, a single burr-hole technique was a successful definitive treatment, with an average period of 23 months. CONCLUSIONS: Third ventricular CSF cysts of thalamic origin most commonly present with hydrocephalus. They can be safely definitively treated via endoscopic fenestration to the CSF circulation using a single burr-hole technique. Long-term follow-up shows lasting improvement in symptoms without reaccumulation of the cyst.

Neuroanatomy of the kisspeptin signaling system in mammals: comparative and developmental aspects.

Our understanding of kisspeptin and its actions depends, in part, on a detailed knowledge of the neuroanatomy of the kisspeptin signaling system in the brain. In this chapter, we will review our current knowledge of the distribution of kisspeptin cells, fibers, and receptors in the mammalian brain, including the development, phenotype, and projections of different kisspeptin subpopulations. A fairly consistent picture emerges from this analysis. There are two major groups of kisspeptin cell bodies: a large number in the arcuate nucleus (ARC) and a smaller collection in the rostral periventricular area of the third ventricle (RP3V) of rodents and preoptic area (POA) of non-rodents. Both sets of neurons project to GnRH cell bodies, which contain Kiss1r, and the ARC kisspeptin population also projects to GnRH axons in the median eminence. ARC kisspeptin neurons contain neurokinin B and dynorphin, while a variable percentage of those cells in the RP3V of rodents contain galanin and/or dopamine. Neurokinin B and dynorphin have been postulated to contribute to the control of GnRH pulses and sex steroid negative feedback, while the role of galanin and dopamine in rostral kisspeptin neurons is not entirely clear. Kisspeptin neurons, fibers, and Kiss1r are found in other areas, including widespread areas outside the hypothalamus, but their physiological role(s) in these regions remains to be determined.

Shh and Gli3 regulate formation of the telencephalic-diencephalic junction and suppress an isthmus-like signaling source in the forebrain.

In human holoprosencephaly (HPE), the forebrain does not separate fully into two hemispheres. Further, the border between the telencephalon and diencephalon, the telencephalic/diencephalic junction (TDJ), is often indistinct, and the ventricular system can be blocked at the third ventricle, creating a forebrain 'holosphere'. Mice deficient in Sonic Hedgehog (Shh) have previously been described to show HPE and associated cyclopia. Here we report that the third ventricle is blocked in Shh null mutants, similar to human HPE, and that characteristic telencephalic and diencephalic signaling centers, the cortical hem and zona limitans intrathalamica (ZLI), are merged, obliterating the TDJ. The resulting forebrain holosphere comprises Foxg1-positive telencephalic- and Foxg1-negative diencephalic territories. Loss of one functional copy of Gli3 in Shh nulls rescues ventricular collapse and substantially restores the TDJ. Characteristic regional gene expression patterns are rescued on the telencephalic side of the TDJ but not in the diencephalon. Further analysis of compound Shh;Gli3 mutants revealed an unexpected type of signaling center deregulation. In Shh;Gli3 mutants, adjacent rings of Fgf8 and Wnt3a expression are induced in the diencephalon at the ZLI, reminiscent of the Fgf8/Wnt1-expressing isthmic organizer. Neither Shh nor Gli3 single mutants show this forebrain double ring of Fgf/Wnt expression; thus both Shh and Gli3 are independently required to suppress it. Adjacent tissue is not respecified to a midbrain/hindbrain fate, but shows overgrowth, consistent with ectopic mitogen expression. Our observations indicate that the separation of the telencephalon and diencephalon depends on interactions between Shh and Gli3, and, moreover, demonstrate that both Shh and Gli3 suppress a potential Fgf/Wnt signaling source in the forebrain. That optional signaling centers are actively repressed in normal development is a striking new insight into the processes of vertebrate brain development.

Persisting embryonal infundibular recess.

Persisting embryonal infundibular recess (PEIR) is a rare anomaly of the third ventricular floor that has an unclear pathogenesis. In all 7 previously described cases, PEIR was present in adult patients and was invariably associated with hydrocephalus and, in 4 reported cases, with an empty sella. These associated findings led to speculations about the role of increased intraventricular pressure in the development of PEIR. In the present case, PEIR was found in a 24-year-old man without the presence of hydrocephalus or empty sella. Disorders of pituitary function had been present since childhood. Magnetic resonance imaging revealed a cystic expansion in an enlarged sella turcica. A communication between the third ventricle and the sellar cyst was suspected but not apparent. During transcranial surgery, the connection was confirmed. Later, higher-quality MR imaging investigations clearly showed a communication between the third ventricle and the sellar cyst through a channel in the tubular pituitary stalk. This observation and knowledge about the embryology of this region suggests that PEIR may be a developmental anomaly caused by failure of obliteration of the distal part of primary embryonal diencephalic evagination. Thus, PEIR is an extension of the third ventricular cavity into the sella. Although PEIR is a rare anomaly, it is important to identify when planning a procedure on cystic lesions of the sella. Because attempts at removal using the transsphenoidal approach would lead to a communication between the third ventricle and the nasal cavity, a watertight reconstruction of the sellar floor is necessary.

microRNA-449 is a putative regulator of choroid plexus development and function.

microRNAs are short RNA molecules that are often expressed in specific tissues and regulate a variety of developmental processes. We used locked nucleic acid probes in in situ hybridisation reactions to study the distribution of microRNA-449 (miR449) during mouse embryonic development in order to obtain clues about its function/s. Between E9.75 and E11.5, miR449 was found to be expressed specifically in the developing roof plate of the fourth ventricle within the domain of roof plate marker, Lmx1a. From E12.5 onwards, this expression became restricted to the epithelial cell layer of the fourth ventricle choroid plexus. MiR449 also became detectable specifically in the choroid plexuses of the lateral and 3rd ventricles at E13.5 and E15.5, respectively. Northern blot analysis of adult brain also showed a selective and enriched expression in the choroid plexus tissue. Potential target genes regulated by miR449 were selected for experimental validation in luciferase-reporter assays and the transcription factor E2f5, which regulates CSF production, was verified as a miR449 target gene. Taken together, these findings suggest that miR449 has a specific role in the development and functioning of choroid plexuses.

Microsurgical and endoscopic anatomy of Liliequist's membrane: a complex and variable structure of the basal cisterns.

OBJECTIVE: Descriptions of Liliequist's membrane, as reported in the literature, vary considerably. In our cadaveric study of Liliequist's membrane, we attempted to clarify and define its anatomic features and boundaries, as well as its relationship with surrounding neurovascular structures. We describe the embryology of this membrane as a remnant of the primary tentorium. The clinical significance of our findings is discussed with respect to third ventriculostomy and surgical approaches to basilar tip aneurysms, suprasellar arachnoid cysts, and perimesencephalic hemorrhage. METHODS: Thirteen formalin-fixed adult cadaveric heads were injected with colored silicone. After endoscopic exploration of Liliequist's membrane, a bilateral frontal craniotomy was performed, and the frontal lobes were removed to fully expose Liliequist's membrane. RESULTS: Liliequist's membrane is a complex and highly variable structure that is composed of either a single membrane or two leaves. The membrane was absent in two specimens without any clear demarcation between the interpeduncular, prepontine, and chiasmatic cisterns. CONCLUSION: Understanding the variable anatomy of Liliequist's membrane is important, particularly to improve current and forthcoming microsurgical and endoscopic neurosurgical procedures. It is important as a surgical landmark in various neurosurgical operations and in the physiopathology of several pathological processes (suprasellar arachnoid cysts and perimesencephalic hemorrhage).

Mu opioid receptors are expressed on radial glia but not migrating neuroblasts in the late embryonic mouse brain.

Mu opioid receptor ligands such as morphine and met-enkephalin are known to modulate normal brain development by perturbing gliogenesis and inhibiting neuronal proliferation. Surprisingly, the distribution of the mu opioid receptor (MOR) in the embryonic brain, especially in proliferative regions, is poorly defined and subject to conflicting reports. Using an immunohistochemical approach, we found that MOR protein was expressed in the neuroepithelia of the lateral ventricles, third ventricle, and aqueduct within the late embryonic (E15.5 and E18.5) mouse brain. In contrast to the ventricular neuroepithelia, the proliferative external granule layer of the embryonic cerebellum did not express MOR protein, although the Purkinje cell layer did. Within the ventricular neuroepithelium, GLAST-positive radial glia that incorporate BrdU expressed MOR, while migrating neuroblasts (doublecortin-positive) do not. BrdU labeling of proliferating cells showed an anterior to posterior gradient of proliferation (P<0.05), while an opposing posterior to anterior gradient of MOR expression (P<0.05) was found. The localization of MOR immunoreactivity within the embryonic ventricular neuroepithelia is consistent with a role for opioids in modulating neurogenesis.

New insights on Saccus vasculosus evolution: a developmental and immunohistochemical study in elasmobranchs.

The saccus vasculosus (SV) is a circumventricular organ of the hypothalamus of many jawed fishes whose functions have not yet been clarified. It is a vascularized neuroepithelium that consists of coronet cells, cerebrospinal fluid-contacting (CSF-c) neurons and supporting cells. To assess the organization, development and evolution of the SV, the expression of glial fibrillary acidic protein (GFAP) and the neuronal markers gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD; the GABA synthesizing enzyme), neuropeptide Y (NPY), neurophysin II (NPH), tyrosine hydroxylase (TH; the rate-limiting catecholamine-synthesizing enzyme) and serotonin (5-HT), were investigated by immunohistochemistry in developing and adult sharks. Coronet cells showed GFAP immunoreactivity from embryos at stage 31 to adults, indicating a glial nature. GABAergic CSF-c neurons were evidenced just when the primordium of the SV becomes detectable (at stage 29). Double immunolabeling revealed colocalization of NPY and GAD in these cells. Some CSF-c cells showed TH immunoreactivity in postembryonic stages. Saccofugal GABAergic fibers formed a defined SV tract from the stage 30 and scattered neurosecretory (NPH-immunoreactive) and monoaminergic (5-HT- and TH-immunoreactive) saccopetal fibers were first detected at stages 31 and 32, respectively. The early differentiation of GABAergic neurons and the presence of a conspicuous GABAergic saccofugal system are shared by elasmobranch and teleosts (trout), suggesting that GABA plays a key function in the SV circuitry. Monoaminergic structures have not been reported in the SV of bony fishes, and were probably acquired secondarily in sharks. The existence of saccopetal monoaminergic and neurosecretory fibers reveals reciprocal connections between the SV and hypothalamic structures which have not been previously detected in teleosts.

Fetal biometry: size and configuration of the third ventricle.

PURPOSE: To evaluate the normal configuration and size of the third ventricle in second and third trimester fetuses in a normal population, and to compare our values with those of previously published studies. MATERIAL AND METHODS: Evaluation of fetal third ventricular width and configuration was obtained by antenatal ultrasonography in 474 fetuses with gestational age between 12 weeks and term (mean 28 weeks). Percentiles for third ventricle width were estimated by combining separate fractional polynominal regression models fitted to the mean and standard deviation, assuming that the measurements had a normal distribution at each gestational age. Appearance of the third ventricle was correlated with each gestational age. RESULTS: The third ventricle could be visualized in 471 (99%) of 474 fetuses. The 97th percentile of the third ventricle in preterm fetuses was measured as 3.6 mm in size. The third ventricle was seen as a single echogenic line in 153 (32.4%) of 474 fetuses. Two-hundred-and-ninety-nine (61.5%) of all fetuses had parallel echogenic lines outlining a fluid-filled lumen. V-shaped third ventricular configuration was seen in only 28 (5.9%) of the fetuses. From 24 weeks to term, parallel echogenic lines were the most commonly (83.7% to 79.6%) encountered configuration for the third ventricle. CONCLUSION: The 97th percentile of the third ventricle in preterm fetuses was measured as 3.6 mm in size. In the early second trimester, 77% of the fetuses had a single echogenic line appearance on ultrasonography. As the brain and ventricular structures mature, a parallel echogenic line becomes the prominent ultrasonography appearance (>80% of fetuses) in third trimester healthy fetuses.