Proliferation of Leptomeningeal Cells in Delayed Neuronal Death in Gerbils

Kataoka, Yosky; Cui, Yilong; Tamura, Yasuhisa; Yamada, Hisao

doi:10.1267/ahc.37.81

Cited by 2 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As well as in the brain parenchyma, a part of the substances, at least, likely reached the leptomeningeal cells by the cerebrospinal fluid, since the number of proliferating leptomeningeal cells in the SD-induced side was 3 times that on the contralateral side (data not shown). Furthermore, in an animal model of ischemic neuronal death in the hippocampus, remote action by such substances on the leptomeninges was observed [19]. Taken together, the present study using adult rats suggests that neural activation facilitates a proliferative response by cortical cells and maintains reorganization of the tissue throughout life.…”

Section: Discussionsupporting

confidence: 61%

Neural Activity-Dependent Cellular Proliferation in the Rat Cerebral Cortex

Kataoka

Tamura

Cui

et al. 2005

Acta Histochem. Cytochem

Self Cite

View full text Add to dashboard Cite

In recent years, studies on cell regeneration in the adult mammalian central nervous system have brought about the possibility of new strategies for treating neurological disorders. Many researchers have examined molecular/cellularbased approaches in vitro, while little has been determined about the modulatory processes affecting cellular proliferation and differentiation in vivo. We report here a new strategy to investigate cellular proliferation, differentiation, and regeneration using an experimental animal model for functional activation of the cerebral cortex in rats. The unilateral cerebral cortex was extensively activated by induction of cortical spreading depression (SD), characterized as propagation of neuronal/glial membrane depolarization. Cellular proliferation in the animals was assessed using histochemical studies with BrdU, an analog of thymidine. SD resulted in a dramatic increase in BrdU-labeled cells in the cortical hemisphere that had undergone the SD, depending on the number of elicited SD events. Immunohistochemical studies revealed that 53% of the BrdUlabeled cells in the SD-generated cortex were immunopositive for NG2, a maker of oligodendrocyte progenitor cells, while 25% were immunopositive for OX-42, a maker of microglia, at 3 days after SD. These studies indicate that neural activation induces cellular proliferation in the cerebral cortex, and that the cells subsequently differentiate into glial progenitors or microglia within 3 days.

show abstract

Section: Discussionsupporting

confidence: 61%

Neural Activity-Dependent Cellular Proliferation in the Rat Cerebral Cortex

Kataoka

Tamura

Cui

et al. 2005

Acta Histochem. Cytochem

Self Cite

View full text Add to dashboard Cite

show abstract

“… 34 In contrast to neurons, astrocytes as well as ependymal and leptomeningeal cells have a slow turnover. 77 , 78 , 79 , 80 In particular, the impact of the loss of ependymocytes and leptomeningeal cells that are in direct contact with the CSF as a monolayer lining the ventricles and meninges, respectively, would most likely be undetectable through the analysis of the expression of the transgene in tissue punches. This could explain why, despite the observed differences in SGSH levels in CSF, there are no significant differences in tissue Sgsh expression among the dogs, with >30 samples/dog of encephalon analyzed.…”

Section: Discussionmentioning

confidence: 99%

Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal

Matarazzo

Haurigot

Jaén

et al. 2021

Molecular Therapy - Methods & Clinical Development

View full text Add to dashboard Cite

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 10 13 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA. Periodic monitoring of CSF and blood, clinical and neurological evaluations, and magnetic resonance and ultrasound imaging of target organs demonstrated no toxicity related to treatment. AAV9-mediated gene transfer resulted in detection of sulfamidase activity in CSF throughout the study. Analysis at tissue level showed widespread sulfamidase expression and activity in the absence of histological findings in any region of encephalon, spinal cord, or dorsal root ganglia. Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS.

show abstract

Proliferation of Leptomeningeal Cells in Delayed Neuronal Death in Gerbils

Cited by 2 publications

References 17 publications

Neural Activity-Dependent Cellular Proliferation in the Rat Cerebral Cortex

Neural Activity-Dependent Cellular Proliferation in the Rat Cerebral Cortex

Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal

Contact Info

Product

Resources

About