Laurent Sakka

Anatomy of the human thalamus based on spontaneous contrast and microscopic voxels in high-field magnetic resonance imaging.

BACKGROUND Since the pioneering studies of human thalamic anatomy based on histology and binding techniques, little new work has been done to bring this knowledge into clinical practice. OBJECTIVE With the advent of magnetic resonance imaging (MRI) we hypothesized that it was possible, in vitro, to make use of high spontaneous MRI contrasts between white and grey matter to directly identify the subcompartmentalisation of the thalamus. METHODS An anatomic specimen was imaged at high field (4.7 T) (basal ganglia plus thalamus block; 3-dimensional (3D) T1-weighted spin echo sequence; matrix, 256 × 256 × 256; isotropic voxel, 0.250 mm/edge; total acquisition time, 14 hours 30 minutes). Nuclei were manually contoured on the basis of spontaneous contrasted structures; labeling relied on 3D identification from classic knowledge; stereotactic location of centers of nuclei was computed. RESULTS Almost all intrathalamic substructures, nuclei, and white matter laminae were identified. Using 3D analysis, a simplified classification of intrathalamic nuclei into 9 groups was proposed, based on topographic MRI anatomy, designed for clinical practice: anterior (oral), posterior, dorsal, intermediate, ventral, medial, laminar, superficial, and related (epi and metathalamus). The overall 4.7-T anatomy matches that presented in the atlases of Schaltenbrand and Bailey (1959), Talairach et al (1957), and Morel et al (1997). CONCLUSION It seems possible to identify the subcompartments of the thalamus by spontaneous MRI contrast, allowing a tissue architectural approach. In addition, the MRI tissue architecture matches the earlier subcompartmentalization based on cyto- and chemoarchitecture. This true 3D anatomic study of the thalamus may be useful in clinical neuroscience and neurosurgical applications.

Maps of the adult human hypothalamus.

The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.

Anatomy of the Spinal Meninges

BACKGROUND: The spinal meninges have received less attention than the cranial meninges in the literature, although several points remain debatable and poorly understood, like their phylogenesis, their development, and their interactions with the spinal cord. Their constancy among the chordates shows their crucial importance in central nervous system homeostasis and suggests a role far beyond mechanical protection of the neuraxis. OBJECTIVE: This work provides an extensive study of the spinal meninges, from an overview of their phylogenesis and embryology to a descriptive and topographic anatomy with clinical implications. It examines their involvement in spinal cord development, functioning, and repair. METHODS: This work is a review of the literature using PubMed as a search engine on Medline. RESULTS: The stages followed by the meninges along the phylogenesis could not be easily compared with their development in vertebrates for methodological aspects and convergence processes throughout evolution. The distinction between arachnoid and pia mater appeared controversial. Several points of descriptive anatomy remain debatable: the functional organization of the arterial network, and the venous and lymphatic drainages, considered differently by classical anatomic and neuroradiological approaches. Spinal meninges are involved in neurodevelopment and neurorepair producing neural stem cells and morphogens, in cerebrospinal fluid dynamics and neuraxis functioning by the synthesis of active molecules, and the elimination of waste products of central nervous system metabolism. CONCLUSION: The spinal meninges should be considered as dynamic functional formations evolving over a lifetime, with ultrastructural features and functional interactions with the neuraxis remaining not fully understood. ABBREVIATIONS: CNS, central nervous system D, day LMD, limited dorsal myeloschisis

SCO-Spondin Derived Peptide NX210 Induces Neuroprotection In Vitro and Promotes Fiber Regrowth and Functional Recovery after Spinal Cord Injury

In mammals, the limited regenerating potential of the central nervous system (CNS) in adults contrasts with the plasticity of the embryonic and perinatal periods. SCO (subcommissural organ)-spondin is a protein secreted early by the developing central nervous system, potentially involved in the development of commissural fibers. SCO-spondin stimulates neuronal differentiation and neurite growth in vitro. NX210 oligopeptide was designed from SCO-spondins specific thrombospondin type 1 repeat (TSR) sequences that support the main neurogenic properties of the molecule. The objective of this work was to assess the neuroprotective and neuroregenerative properties of NX210 in vitro and in vivo for the treatment of spinal cord injury (SCI). In vitro studies were carried out on the B104 neuroblastoma cell line demonstrating neuroprotection by the resistance to oxidative damage using hydrogen peroxide and the measure of cell viability by metabolic activity. In vivo studies were performed in two rat models of SCI: (1) a model of aspiration of dorsal funiculi followed by the insertion of a collagen tube in situ to limit collateral sprouting; white matter regeneration was assessed using neurofilament immunostaining; (2) a rat spinal cord contusion model to assess functional recovery using BBB scale and reflex testing. We demonstrate for the first time that NX210 (a) provides neuroprotection to oxidative stress in the B104 neuroblastoma cells, (b) stimulates axonal regrowth in longitudinally oriented neofibers in the aspiration model of SCI and (c) significantly improves functional recovery in the contusive model of SCI.

Human Foramen Magnum Area and Posterior Cranial Fossa Volume Growth in Relation to Cranial Base Synchondrosis Closure in the Course of Child Development

BACKGROUND To date, no study has compared the evolution of the foramen magnum area (FMA) and the posterior cranial fossa volume (PCFV) with the degree of cranial base synchondrosis ossification. OBJECTIVE To illustrate these features in healthy children. METHODS The FMA, the PCFV, and the ossification of 12 synchondroses according to the Madeline and Elster scale were retrospectively analyzed in 235 healthy children using millimeter slices on a computed tomography scan. RESULTS The mean FMA of 6.49 cm in girls was significantly inferior to the FMA of 7.67 cm in boys (P < .001). In both sexes, the growth evolved in a 2-phase process, with a phase of rapid growth from birth to 3.75 years old (yo) followed by a phase of stabilization. In girls, the first phase was shorter (ending at 2.6 yo) than in boys (ending at 4.33 yo) and proceeded at a higher rate. PCFV was smaller in girls (P < .001) and displayed a biphasic pattern in the whole population, with a phase of rapid growth from birth to 3.58 yo followed by a phase of slow growth until 16 yo. In girls, the first phase was more active and shorter (ending at 2.67 yo) than in boys (ending at 4.5 yo). The posterior interoccipital synchondroses close first, followed by the anterior interoccipital and occipitomastoidal synchondroses, the lambdoid sutures simultaneously, then the petro-occipital and spheno-occipital synchondroses simultaneously. CONCLUSION The data provide a chronology of synchondrosis closure. We showed that FMA and PCFV are constitutionally smaller in girls at birth (P ≤ .02) and suggest that a sex-related difference in the FMA is related to earlier closure of anterior interoccipital synchondroses in girls (P = .01). ABBREVIATIONS AIOS, anterior interoccipital synchondrosesFMA, foramen magnum areaLS, lambdoid suturesOMS, occipitomastoidal synchondrosesPCFV, posterior cranial fossa volumePIOS, posterior interoccipital synchondrosesPOS, petro-occipital synchondrosesSOS, spheno-occipital synchondrosisyo, years old.

Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation

Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (p<2.26 10−7), -24.1 (p<5.6 10−9) and -17.7 (p<1.2 10−7). CCNE1, AURKA, IGF2, MYCN and ERBB2 were more moderately down-regulated by both molecules. Glioma markers E2F1, DAPK1 and CCND1 were down-regulated. Citalopram displayed more powerful action with broader and distinct spectrum of action than escitalopram.

Advanced Neuroimaging with Computed Tomography Scanning

The x-ray computed tomography (CT) is well known as a useful imaging method and thus CT images have continuingly been used for many applications, especially in medical fields. This book discloses recent advances and new ideas in theories and applications for CT imaging and its analysis. The 16 chapters selected in this book cover not only the major topics of CT imaging and analysis in medical fields, but also some advanced applications for forensic and industrial purposes. These chapters propose state-of-the-art approaches and cutting-edge research results.