Endoscopic transorbital resection of the temporal lobe: anatomic qualitative and quantitative study

ObjectiveStarting from an anatomic study describing the possibility of reaching the temporal region through an endoscopic transorbital approach, many clinical reports have now demonstrated the applicability of this strategy when dealing with intra-axial lesions. The study aimed to provide both a qualitative anatomic description of the temporal region, as seen through a transorbital perspective, and a quantitative analysis of the amount of temporal lobe resection achievable via this route.Material and methodsA total of four cadaveric heads (eight sides) were dissected at the Laboratory of Surgical Neuroanatomy (LSNA) of the University of Barcelona, Spain. A stepwise description of the resection of the temporal lobe through a transorbital perspective is provided. Qualitative anatomical descriptions and quantitative analysis of the amount of the resection were evaluated by means of pre- and post-dissection CT and MRI scans, and three-dimensional reconstructions were made by means of BrainLab®Software.ResultsThe transorbital route gives easy access to the temporal region, without the need for extensive bone removal. The resection of the temporal lobe proceeded in a subpial fashion, mimicking what happens in a surgical scenario. According to our quantitative analysis, the mean volume removed was 51.26%, with the most superior and lateral portion of the temporal lobe being the most difficult to reach.ConclusionThis anatomic study provides qualitative and quantitative details about the resection of the temporal lobe via an endoscopic transorbital approach. Our results showed that the resection of more than half of the temporal lobe is possible through this surgical corridor. While the anterior, inferior, and mesial portions of the temporal lobe were easily accessible, the most superior and lateral segment was more difficult to reach and resect. Our study serves as an integration to the current anatomic knowledge and clinical practice knowledge highlighting and also as a starting point for further anatomic studies addressing more selected segments of the temporal lobe, i.e., the mesial temporal region

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy

Aims: Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number of neurodegenerative conditions. To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which exhibits axonal degeneration in spinal cords and motor disability. The disease is caused by loss of function of the ABCD1 transporter, involved in the import and degradation of very long-chain fatty acids (VLCFA) in peroxisomes. Oxidative stress due to VLCFA excess appears early in the neurodegenerative cascade. Results: In this study, we demonstrate by redox proteomics that oxidative damage to proteins specifically affects five key enzymes of glycolysis and TCA (Tricarboxylic acid) cycle in spinal cords of Abcd1(-) mice and pyruvate kinase in human X-ALD fibroblasts. We also show that NADH and ATP levels are significantly diminished in these samples, together with decrease of pyruvate kinase activities and GSH levels, and increase of NADPH. Innovation: Treating Abcd1(-) mice with the antioxidants N-acetylcysteine and alpha-lipoic acid (LA) prevents protein oxidation; preserves NADH, NADPH, ATP, and GSH levels; and normalizes pyruvate kinase activity, which implies that oxidative stress provoked by VLCFA results in bioenergetic dysfunction, at a presymptomatic stage. Conclusion: Our results provide mechanistic insight into the beneficial effects of antioxidants and enhance the rationale for translation into clinical trials for X-adrenoleukodystrophy. Antioxid. Redox Signal. 15, 2095-2107

Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2 ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2 mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms, whereas inflammation allegedly plays no role in AMN. How VLCFA accumulation leads to neurodegeneration and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. To gain insights into these questions, we undertook a transcriptomic approach followed by a functional-enrichment analysis in spinal cords of the animal model of AMN, the Abcd1− null mice, and in normal-appearing white matter of cAMN and cALD patients. We report that the mouse model shares with cAMN and cALD a common signature comprising dysregulation of oxidative phosphorylation, adipocytokine and insulin signaling pathways, and protein synthesis. Functional validation by quantitative polymerase chain reaction, western blots and assays in spinal cord organotypic cultures confirmed the interplay of these pathways through IkB kinase, being VLCFA in excess a causal, upstream trigger promoting the altered signature. We conclude that X-ALD is, in all its variants, a metabolic/inflammatory syndrome, which may offer new targets in X-ALD therapeutics

Mejoramiento de la reproducción bovina: leche, carne y calidad seminal

La eficiencia reproductiva tiene un impacto importante en la rentabilidad de la industria ganadera. Un porcentaje significativo de insuficiencia reproductiva es atribuible a la subfertilidad del toro (Butler et al., 2020). La reproducción es un rasgo muy complejo que involucra la concepción, la cual está influenciada mayormente por factores ambientales, el estado nutricional y de salud del animal (Montoya-Monsalve et al., 2021). La tasa de concepción depende de los rasgos de fertilidad de la vaca y del toro, y sobre este último un aspecto fundamental es el análisis de la calidad del esperma (Butler et al., 2020). En sistemas extensivos para la cría de bovino de carne, las evaluaciones de fertilidad respaldan apenas un 20% de los toros aptos para la monta (Montoya- Monsalve et al., 2021). En consecuencia, la disponibilidad tan baja de toros con fertilidad aceptable es un problema, más aún cuando al número de toros infértiles o sub fértiles se suman toros que han perdido la condición de fértiles por enfermedades infecciosas durante su vida productiva.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro de Investigaciones Agronómicas (CIA)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental de Ganado Lechero Alfredo Volio Mata (EEAVM

Defining the lateral limits of the endoscopic endonasal transtuberculum transplanum approach: anatomical study with pertinent quantitative analysis

OBJECTIVE The extended endoscopic endonasal transtuberculum transplanum approach is currently used for the surgical treatment of selected midline anterior skull base lesions. Nevertheless, the possibility of accessing the lateral aspects of the planum sphenoidale could represent a limitation for such an approach. To the authors' knowledge, a clear definition of the eventual anatomical boundaries has not been delineated. Hence, the present study aimed to detail and quantify the maximum amount of bone removal over the planum sphenoidale required via the endonasal pathway to achieve the most lateral extension of such a corridor and to evaluate the relative surgical freedom. METHODS Six human cadaveric heads were dissected at the Laboratory of Surgical NeuroAnatomy of the University of Barcelona. The laboratory rehearsals were run as follows: 1) preliminary predissection CT scans, 2) the endoscopic endonasal transtuberculum transplanum approach (lateral limit: medial optocarotid recess) followed by postdissection CT scans, 3) maximum lateral extension of the transtuberculum transplanum approach followed by postdissection CT scans, and 4) bone removal and surgical freedom analysis (a nonpaired Student t-test). A conventional subfrontal bilateral approach was used to evaluate, from above, the bone removal from the planum sphenoidale and the lateral limit of the endonasal route. RESULTS The endoscopic endonasal transtuberculum transplanum approach was extended at its maximum lateral aspect in the lateral portion of the anterior skull base, removing the bone above the optic prominence, that is, the medial portion of the lesser sphenoid wing, including the anterior clinoid process. As expected, a greater bone removal volume was obtained compared with the approach when bone removal is limited to the medial optocarotid recess (average 533.45 vs 296.07 mm2; p < 0.01). The anteroposterior diameter was an average of 8.1 vs 15.78 mm, and the laterolateral diameter was an average of 18.77 vs 44.54 mm (p < 0.01). The neurovascular contents of this area were exposed up to the insular segment of the middle cerebral artery. The surgical freedom analysis revealed a possible increased lateral maneuverability of instruments inserted in the contralateral nostril compared with a midline target (average 384.11 vs 235.31 mm2; p < 0.05). CONCLUSIONS Bone removal from the medial aspect of the lesser sphenoid wing, including the anterior clinoid process, may increase the exposure and surgical freedom of the extended endoscopic endonasal transtuberculum transplanum approach over the lateral segment of the anterior skull base. Although this study represents a preliminary anatomical investigation, it could be useful to refine the indications and limitations of the endoscopic endonasal corridor for the surgical management of skull base lesions involving the lateral portion of the planum sphenoidale