Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants

Mukhida, Karim; Baker, Kim; Sadi, Damaso; Mendez, Ivar

doi:10.1523/jneurosci.21-10-03521.2001

Cited by 58 publications

(35 citation statements)

References 76 publications

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“…Various types of cells prepared with a variety of different methwith the transplantation procedure have prevented precise evaluation of host-graft interactions (15). ods and combinations have been transplanted into many tissue types, including retina, in animal models of the There is an increasing awareness of the environmental changes in the host retina triggered by photoreceptor dysfunctional or degenerating CNS (19,26,30,34,35,43). However, most have achieved only a limited degree of degeneration and surgical manipulation (20)(21)(22)36).…”

Section: Introductionmentioning

confidence: 99%

Chondroitinase ABC Treatment Enhances Synaptogenesis between Transplant and Host Neurons in Model of Retinal Degeneration

et al. 2007

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Although recent studies revealed chondroitinase ABC (ChABC), an enzyme that degrades chondroitin sulfate proteoglycans, promotes CNS regeneration in vivo, the usefulness of its application for transplantation is not clear. We investigated if treatment with ChABC can promote synapse formation between graft and host neurons following retinal transplantation. Dissociated retinal cells were prepared from neonatal Nrl-GFP transgenic mice in which rod photoreceptors and their progenitor cells are labeled with GFP. Each cell suspension with or without ChABC (Nrl/ChABC group and Nrl group, respectively) was injected subretinally into the eyes of mice following chemically induced photoreceptor degeneration. The survival and functional integration of the transplanted photoreceptors were examined by histologically and electrophysiologically. Up to 4 weeks after transplantation, almost all the grafted GFP+ photoreceptor cells were widely distributed at the outer margin of the host retina where the photoreceptor layer was located originally. In the Nrl/ChABC group, 33.6% of the GFP+ photoreceptors elaborated neurites horizontally or vertically, and 4.6% elaborated neurites toward the retina. These neurites extended over the glial seal at the graft-host interface, and established synaptic contacts with neurons in the host retina as determined by confocal microscopy and three-dimensional analysis. Although 30.7% cells (p = 0.68) elaborated neurites in the Nrl group, only 1.2% cells (p < 0.05) projected neurites towards the host tissue and synaptic contacts were rare. Our results illustrate the potential utility of ChABC for enhancing synaptogenesis between transplanted neurons and host retina.

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Section: Introductionmentioning

confidence: 99%

Chondroitinase ABC Treatment Enhances Synaptogenesis between Transplant and Host Neurons in Model of Retinal Degeneration

et al. 2007

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“…Experiments performed by Mukhida and colleagues showed considerable improvement in behavioral control with dopaminergic-destined fetal ventral mesencephalic transplants into the striatum, substantia nigra, and subthalamic nucleus that seemed to improve behavioral recovery better than the typical single transplant alone [194]. Clearly there may be a benefit to such extended transplantation but there are two major issues drawing the practicality of such strategies into question.…”

Section: Adaptation Of Transplanted Neural Cells To the Endogenous Homentioning

confidence: 99%

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Sandstrom¹,

Anderson²,

Jayaprakash³

et al. 2018

Neuroplasticity - Insights of Neural Reorganization

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Although stem cell transplant therapy offers considerable promise for deteriorative diseases, the efficacy of its application may be mitigated by endogenous compensatory mechanisms in the host brain. Plastic compensation follows neurodegeneration, beginning at its very onset and minimizing early symptom expression. As researchers attempt to correlate symptom remission with the ability of transplanted cells to adopt specific cell phenotypes, they need to be vigilant of the possibility that competing, local compensatory effects may be altering the outcome. Clearly plastic compensatory mechanisms could confound desired transplant-derived improvements by supplanting the beneficial contributions of the transplants. As circuit-level adaptations occur, more explicit explorations of their relevance to neuronal transplantation success are needed. Conceptual models of undirected transplanted cells adopting preconceived appropriate roles require revision. The notion that newly transplanted neuronal precursors will incorporate themselves into host circuitry with mutual cooperation across both parties (i.e., transplant and host) without some symbiosis-promoting mechanism is naïve. Undirected local circuits could react to newly transplanted additions as intruders. We advocate that appropriate signaling from transplanted cells to the host environment is required to optimize the therapeutic relevance of transplantation. This review surveys critical signaling mechanisms that might promote symbiotic interdependence between the host and new transplants.

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“…68 The capillary was left in place for an additional 5 minutes after each deposit before being retracted. The stereotactic coordinates for transplantation were as follows (in mm and with reference to the bregma and dura): 1) AP ϩ1.3, ML Ϫ2.1, and DV Ϫ5.5 and Ϫ4.3; 2) AP ϩ0.6, ML, Ϫ2.9, and DV Ϫ5.5 and Ϫ4.3; and 3) AP ϩ0.3, ML Ϫ3.7, and DV Ϫ5.5 and Ϫ4.3, with the incisor bar set 3.3 mm below the IA for all 3 sets of coordinates.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…Human nuclei immunohistochemistry was performed on every 4th brain section by using a standard avidin-biotin complex. 68 After washing the sections in 0.1M PB, we immersed them in 3% H 2 O 2 and 10% methanol in 0.1M PB for 10 minutes. After rinsing the sections in 0.1M PB again, we treated them with 5% normal horse serum for 1 hour and 0.3% Triton X-100 in 0.1M PB for 1 hour and then incubated them for 16 hours in the same diluent, which also contained mouse antiHuN antibody.…”

Section: Histological Analysismentioning

confidence: 99%

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

Mukhida

Baghbaderani

Hong

et al. 2008

FOC

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Object Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. Methods Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8–10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. Results The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. Conclusions Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.

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Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants

Cited by 58 publications

References 76 publications

Chondroitinase ABC Treatment Enhances Synaptogenesis between Transplant and Host Neurons in Model of Retinal Degeneration

Chondroitinase ABC Treatment Enhances Synaptogenesis between Transplant and Host Neurons in Model of Retinal Degeneration

Plastic Adaptation: A Neuronal Imperative Capable of Confounding the Goals of Stem Cell Replacement Therapy for either Huntington’s or Parkinson’s Disease

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

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