Implantation of Bioactive Growth Factor-Secreting Rods Enhances Fetal Dopaminergic Graft Survival, Outgrowth Density, and Functional Recovery in a Rat Model of Parkinson's Disease

Törnqvist, Nina; Björklund, Lars; Almqvist, Per; Wahlberg, Lars U.; Strömberg, Ingrid

doi:10.1006/exnr.2000.7411

Cited by 54 publications

(22 citation statements)

References 61 publications

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“…GDNF also improved the graft-derived reinnervated volume of adult host striatum, but did not change the pattern of dopaminergic reinnervation, i.e. from diffuse and sparse to dense and patchy (Törnqvist et al, 2000). However, GDNF treatment of mature dopamine grafts did not affect survival and outgrowth from grafted dopamine neurons (Johansson et al, 1995;Winkler et al, 2006), but enhanced nerve fiber formation within the grafts, a phenomenon also found using other factors .…”

Section: Introductionmentioning

confidence: 65%

Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures

et al. 2007

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Glial cell line-derived neurotrophic factor (GDNF) is potent for survival and promotion of nerve fibers from midbrain dopamine neurons. It is also known to exert different effects on specific subpopulations of dopamine neurons. In organotypic tissue cultures, dopamine neurons form two diverse nerve fiber growth patterns, targeting the striatum differently. The aim of this study was to investigate the effect of GDNF on the formation of dopamine nerve fibers. Organotypic tissue cultures of ventral mesencephalon of gdnf gene-deleted mice were studied. The results revealed that dopamine neurons survive in the absence of GDNF. Tyrosine hydroxylase immunoreactivity demonstrated, in gdnf knockout and wildtype cultures, nerve fiber formation with two separate morphologies occurring either in the absence or the presence of astrocytes. The outgrowth that occurred in the absence of astrocytes was unaffected by gdnf deletion, whereas nerve fibers guided by the presence of astrocytes were affected in that they reached significantly shorter distances from the gdnf gene-deleted tissue slice, compared to those measured in wildtype cultures. Treatment with GDNF reversed this effect and increased nerve fiber density independent of genotype. Furthermore, migration of astrocytes reached significantly shorter distances from the tissue slice in GDNF knockout compared to wildtype cultures. Exogenous GDNF increased astrocytic migration in gdnf gene-deleted tissue cultures, comparable to lengths observed in wildtype tissue cultures. In conclusion, cultured midbrain dopamine neurons survive in the absence of GDNF, and the addition of GDNF improved dopamine nerve fiber formation -possibly as an indirect effect of astrocytic stimulation.

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Section: Introductionmentioning

confidence: 65%

Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures

et al. 2007

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“…27,28 The development and clinical application of carmustine-loaded polymers have demonstrated the effectiveness of local chemotherapy against malignant gliomas in experimental models 12 and ongoing clinical trials. 13,14,28 The use of polymer matrices to deliver pharmacotherapy interstitially to the CNS has also been accomplished in experimental models of neurodegenerative disorders, 29 brain edema, 30 and chronic posthemorrhagic vasospasm. 6,31 We have previously described the release kinetics of the DETA/NO-EVAc polymer used in this investigation and demonstrated the favorable pharmacokinetics of this polymer construct for intracranial delivery of exogenous NO.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer

Gabikian

Clatterbuck

Eberhart

et al. 2002

Stroke

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Background and Purpose-A reduction in the local availability of nitric oxide (NO) may play a role in the etiology of chronic cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the toxicity and efficacy of a locally delivered NO donor from a controlled-release polymer in preventing experimental cerebral vasospasm in rats and rabbits, respectively. Methods-Diethylenetriamine/NO (DETA/NO) was incorporated into controlled release ethylene-vinyl acetate (EVAc) polymers. Twenty-eight rats were used in a dose-escalation toxicity study to establish a maximally tolerated dose of DETA/NO-EVAc polymer. In the efficacy experiment, 20 rabbits were assigned to 4 experimental groups (nϭ5 per group): sham operation; SAH only; SAHϩempty EVAc polymer; and SAHϩDETA/NO-EVAc polymer. Treatment was initiated 30 minutes after blood deposition. Basilar artery lumen patency was assessed 72 hours after hemorrhage to evaluate the efficacy of DETA/NO in preventing cerebral vasospasm. Results-In the toxicity study, a dose of 3.4 mg/kg was identified as the LD 20 (dose with 20% mortality during the study period) of this DETA/NO formulation. Brain histology revealed hemorrhage and ischemic changes at the implantation site associated with high concentrations of DETA/NO. In the efficacy study, treatment with DETA/NO-EVAc polymer resulted in a significant decrease in basilar artery vasospasm compared with no treatment (

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“…Indeed, the emerging field of tissue engineering requires accurate delivery of bioactive and/or therapeutic molecules to a specific location. To this end, the use of polymeric delivery vehicles in the form of micro-or nano-spheres/particles to encapsulate the active molecules and maintain a sustained localised delivery to the target site is attractive [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Preferential cell response to anisotropic electro-spun fibrous scaffolds under tension-free conditions

English

Azeem

Gaspar

et al. 2011

J Mater Sci: Mater Med

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Anisotropic alignment of collagen fibres in musculoskeletal tissues is responsible for the resistance to mechanical loading, whilst in cornea is responsible for transparency. Herein, we evaluated the response of tenocytes, osteoblasts and corneal fibroblasts to the topographies created through electro-spinning and solvent casting. We also evaluated the influence of topography on mechanical properties. At day 14, human osteoblasts seeded on aligned orientated electro-spun mats exhibited the lowest metabolic activity (P \ 0.001). At day 5 and at day 7, no significant difference was observed in metabolic activity of human corneal fibroblasts and bovine tenocytes respectively seeded on different scaffold conformations (P [ 0.05). Osteoblasts and corneal fibroblasts aligned parallel to the direction of the aligned orientated electro-spun mats, whilst tenocytes aligned perpendicular to the aligned orientated electro-spun mats. Mechanical evaluation demonstrated that aligned orientated electro-spun fibres exhibited significant higher stress at break values than their random aligned counterparts (P \ 0.006) and random orientated electro-spun fibres exhibited significant higher strain at break values than the aligned orientated scaffolds (P \ 0.006). While maintaining fibre structure, we also developed a co-deposition method of spraying and electro-spinning, which enables the incorporation of microspheres within the three-dimensional structure of the scaffold.

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Implantation of Bioactive Growth Factor-Secreting Rods Enhances Fetal Dopaminergic Graft Survival, Outgrowth Density, and Functional Recovery in a Rat Model of Parkinson's Disease

Cited by 54 publications

References 61 publications

Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures

Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures

Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer

Preferential cell response to anisotropic electro-spun fibrous scaffolds under tension-free conditions

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