Pharmacological MRI of stem cell transplants in the 3-nitroproprionic acid-damaged striatum

TY - JOUR

T1 - Pharmacological MRI of stem cell transplants in the 3-nitroproprionic acid-damaged striatum

AU - Roberts, T J

AU - Price, J

AU - Williams, S C R

AU - Modo, M

PY - 2007/1/5

Y1 - 2007/1/5

N2 - Blood oxygen level dependent (BOLD) pharmacological magnetic resonance imaging (phMRI) affords the noninvasive visualization of brain activity resulting from the administration of pharmacological compounds. Once the compound-responsive cells are lost, no change in activity is expected to occur. This principle therefore allows the assessment of neuronal loss or lack of signal transmission. These investigations can provide evidence of pathology in the absence of significant tissue loss and can be highly specific to determine which type of cell has been lost. Conversely, transplantation of cells replacing the lost neurons should restore normal signal transmission. We here demonstrate the application of phMRI to differentiate between rats with 3-nitroproprionic acid (3-NPA)-induced striatal lesions and 3-NPA-lesioned animals with neural stem cell transplants or controls. 3-NPA-induced lesions mainly involve striatal projection neurons that are responsive to dopamine agonists. The D2-agonist bromocriptine acts on these projection cells and loss of these through 3-NPA administration resulted in a significant decrease of locomotor activity and a substantial attenuation of the BOLD-response in the striatum. In contrast, lesioned animals that were grafted with neural stem cells exhibited an activity pattern akin to controls. Hence, grafting of neural stem cells exerts a functionally significant effect on striatal signal transmission that could underpin behavioral recovery. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved

AB - Blood oxygen level dependent (BOLD) pharmacological magnetic resonance imaging (phMRI) affords the noninvasive visualization of brain activity resulting from the administration of pharmacological compounds. Once the compound-responsive cells are lost, no change in activity is expected to occur. This principle therefore allows the assessment of neuronal loss or lack of signal transmission. These investigations can provide evidence of pathology in the absence of significant tissue loss and can be highly specific to determine which type of cell has been lost. Conversely, transplantation of cells replacing the lost neurons should restore normal signal transmission. We here demonstrate the application of phMRI to differentiate between rats with 3-nitroproprionic acid (3-NPA)-induced striatal lesions and 3-NPA-lesioned animals with neural stem cell transplants or controls. 3-NPA-induced lesions mainly involve striatal projection neurons that are responsive to dopamine agonists. The D2-agonist bromocriptine acts on these projection cells and loss of these through 3-NPA administration resulted in a significant decrease of locomotor activity and a substantial attenuation of the BOLD-response in the striatum. In contrast, lesioned animals that were grafted with neural stem cells exhibited an activity pattern akin to controls. Hence, grafting of neural stem cells exerts a functionally significant effect on striatal signal transmission that could underpin behavioral recovery. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved

U2 - 10.1016/j.neuroscience.2006.09.015

DO - 10.1016/j.neuroscience.2006.09.015

M3 - Article

VL - 144

SP - 100

EP - 109

JO - Neuroscience

JF - Neuroscience

IS - 1

ER -