Intracerebral Transplantation of Porcine Choroid Plexus Provides Structural and Functional Neuroprotection in a Rodent Model of Stroke

Borlongan, Cesario V.; Skinner, S. J. M.; Geaney, Marilyn S.; Vasconcellos, Alfred V.; Elliott, Robert B.; Emerich, Dwaine F.

doi:10.1161/01.str.0000138954.25825.0b

Cited by 121 publications

(102 citation statements)

References 23 publications

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“…Lastly, choroids plexus produce BDNF when transplanted into the ischemic lesion (Borlongan et al, 2004b). Although not investigated directly here, our results suggest that the primarily signal involved in the control of BDNF production originates from ischemically injured neurons.…”

Section: Discussionmentioning

confidence: 67%

Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats

Béjot

Prigent‐Tessier

Cachia

et al. 2011

Neurochemistry International

125

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Although brain-derived neurotrophic factor (BDNF) plays a central role in recovery after cerebral ischemia, little is known about cells involved in BDNF production after stroke.The present study testes the hypothesis that neurons are not the unique source of neosynthesized BDNF after stroke and that non neuronal-BDNF producing cells differ according to the delay after stroke induction. For this purpose, cellular localization of BDNF and BDNF content of each hemisphere were analysed in parallel before and after (4h, 24h and 8d) ischemic stroke in rats. Stroke of different severities was induced by embolization of the brain with variable number of calibrated microspheres allowing us to explore the association between BDNF production and neuronal death severity. The main results are that a) unilateral stroke increased BDNF production in both hemispheres with a more intense and long-lasting effect in the lesioned hemisphere, b) BDNF levels either of the lesioned or unlesioned hemispheres were not inversely correlated to neuronal death severity whatever the delay after stroke onset, c) in the unlesioned hemisphere, stroke resulted in increased BDNF staining in neurons and ependymal cells (at 4h and 24h), d) in the lesioned hemisphere, beside neurons and ependymal cells, microglial cells (at 24h), endothelial cells of cerebral arterioles (at 4h and 24h) and astrocytes (at 8d) exhibited a robust BDNF staining as well. Taken together, overall data suggest that non neuronal cells are able to produce substantial amount of BDNF after ischemic stroke and that more attention should be given to these cells in the design of strategies aimed at improving stroke recovery through BDNFrelated mechanisms.

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Section: Discussionmentioning

confidence: 67%

Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats

Béjot

Prigent‐Tessier

Cachia

et al. 2011

Neurochemistry International

125

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“…Third, many compounds are synthesised by CPs or leptomeninges in health or response to disease or trauma, and secreted into CSF for CNS use, for example, transthyretin, IGF-II and NGF [15,25,26,169].…”

Section: The Need For Csf-brain Isf Exchangementioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

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Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

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“…[1][2][3][4] Encapsulation protects graft cells from potential damage caused by an immune response while allowing the secretion of therapeutic agents from the cells into the surrounding host tissue. Small molecules such as glucose, oxygen, and waste products freely pass through the gel matrix.…”

Section: Introductionmentioning

confidence: 99%

Alginate Composition Effects on a Neural Stem Cell–Seeded Scaffold

Purcell

Singh

Kipke

2009

Tissue Engineering Part C: Methods

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The purpose of this study was to evaluate the effects of alginate composition on the neurotrophic factor release, viability, and proliferation of encapsulated neural stem cells (NSCs), as well as on the mechanical stability of the scaffold itself. Four compositions were tested: a high guluronic acid (68%) and a high mannuronic acid (54%) content alginate, with or without a poly-L-lysine (PLL) coating layer. Enzyme-linked immunosorbent assay was used to quantify the release of brain-derived neurotrophic factor, glial-derived neurotrophic factor, and nerve growth factor from the encapsulated cells. All three factors were detected from encapsulated cells only when a high L-guluronic acid alginate without PLL was used. Additionally, capsules with this composition remained intact more frequently when exposed to solutions of low osmolarity, potentially indicating superior mechanical stability. Alginate beads with a PLL-coated, high D-mannuronic acid composition were the most prone to breakage in the osmotic pressure test, and were too fragile for histology and proliferation assays after 1 week in vitro. NSCs survived and proliferated in the three remaining alginate compositions similarly over the 21-day study course irrespective of scaffold condition. NSC-seeded alginate beads with a high L-guluronic acid, non-PLL-coated composition may be useful in the repair of injured nervous tissue, where the mechanism is the secretion of neuroprotective factors. We verify the neuroprotective effects of medium conditioned by NSCseeded alginate beads on the serum withdrawal-mediated death of PC-12 cells here.

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Intracerebral Transplantation of Porcine Choroid Plexus Provides Structural and Functional Neuroprotection in a Rodent Model of Stroke

Cited by 121 publications

References 23 publications

Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats

Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

Alginate Composition Effects on a Neural Stem Cell–Seeded Scaffold

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