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1.
Nature ; 625(7996): 768-777, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38200313

ABSTRACT

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.


Subject(s)
Cerebrospinal Fluid , Cervical Vertebrae , Drainage , Lymphatic Vessels , Animals , Mice , Aging/metabolism , Cerebrospinal Fluid/metabolism , Cervical Vertebrae/metabolism , Endothelial Cells/metabolism , Fluorescence , Genes, Reporter , Interferon Type I/immunology , Interferon Type I/metabolism , Lymphatic Vessels/physiology , Myocytes, Smooth Muscle/metabolism , Nitric Oxide/metabolism , Nose/physiology , Pharynx/metabolism , Receptors, Adrenergic, alpha/metabolism , Single-Cell Analysis , Signal Transduction
2.
eNeuro ; 11(5)2024 May.
Article in English | MEDLINE | ID: mdl-38688719

ABSTRACT

Glutamatergic mossy cells (MCs) mediate associational and commissural connectivity, exhibiting significant heterogeneity along the septotemporal axis of the mouse dentate gyrus (DG). However, it remains unclear whether the neuronal features of MCs are conserved across mammals. This study compares the neuroanatomy of MCs in the DG of mice and monkeys. The MC marker, calretinin, distinguishes two subpopulations: septal and temporal. Dual-colored fluorescence labeling is utilized to compare the axonal projection patterns of these subpopulations. In both mice and monkeys, septal and temporal MCs project axons across the longitudinal axis of the ipsilateral DG, indicating conserved associational projections. However, unlike in mice, no MC subpopulations in monkeys make commissural projections to the contralateral DG. In monkeys, temporal MCs send associational fibers exclusively to the inner molecular layer, while septal MCs give rise to wide axonal projections spanning multiple molecular layers, akin to equivalent MC subpopulations in mice. Despite conserved septotemporal heterogeneity, interspecies differences are observed in the topological organization of septal MCs, particularly in the relative axonal density in each molecular layer along the septotemporal axis of the DG. In summary, this comparative analysis sheds light on both conserved and divergent features of MCs in the DG of mice and monkeys. These findings have implications for understanding functional differentiation along the septotemporal axis of the DG and contribute to our knowledge of the anatomical evolution of the DG circuit in mammals.


Subject(s)
Axons , Calbindin 2 , Dentate Gyrus , Mice, Inbred C57BL , Animals , Male , Dentate Gyrus/cytology , Dentate Gyrus/anatomy & histology , Calbindin 2/metabolism , Mossy Fibers, Hippocampal/physiology , Mice , Species Specificity , Female
3.
J Korean Neurosurg Soc ; 43(6): 294-9, 2008 Jun.
Article in English | MEDLINE | ID: mdl-19096635

ABSTRACT

OBJECTIVE: To evaluate the clinical characteristics and surgical outcomes of the patients with cervical spondylotic myelopathy associated with athetoid cerebral palsy. METHODS: The authors reviewed the clinical and neurodiagnostic findings, surgical managements and outcomes in six consecutive patients with cervical spondylotic myelopathy associated with athetoid cerebral palsy who had been treated with surgical decompression and fusion procedures between January 1999 and December 2005. The mean age of the 6 patients (four women and two men) at the time of surgery was 42.8 years (range, 31-55 years). The mean follow-up period was 56.5 months (range, 17-112 months). The neurological outcome was evaluated before and after operations (immediately, 6 months after and final follow-up) using grading systems of the walking ability, brachialgia and deltoid power. RESULTS: At immediate postoperative period, after 6 months, and at final follow-up, all patients showed apparent clinical improvements in walking ability, upper extremity pain and deltoid muscle strength. Late neurological deterioration was not seen during follow-up periods. There were no serious complications related to surgery. CONCLUSION: Surgical decompression and stabilization in patients with cervical spondylotic myelopathy associated with athetoid cerebral palsy have been challenging procedure up to now. Our results indicate that early diagnosis and appropriate surgical procedure can effectively improve the clinical symptoms and neurological function in patients with cervical spondylotic myelopathy and athetoid cerebral palsy, even in those with severe involuntary movements.

4.
J Korean Neurosurg Soc ; 44(3): 166-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-19096670

ABSTRACT

Sacral insufficiency fractures are usually known to develop in elderly patients with osteoporosis without definite trauma history. It is difficult to diagnose the sacral insufficiency fracture at an early stage because lower lumbar diseases, concurrently or not, may also be presented with similar symptoms and signs. We report a rare case of sacral insufficiency fracture who was not diagnosed initially but, instead, showed progressively worsening of clinical symptoms and radiological findings after decompression surgery for upper level lumbar stenosis.

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