¹²³ I-Iomazenil Single Photon Emission Computed Tomography Visualizes Recovery of Neuronal Integrity by Bone Marrow Stromal Cell Therapy in Rat Infarct Brain

Abstract

Background and Purpose-This study was aimed to assess whether 123 I-iomazenil (IMZ) single photon emission computed tomography can serially monitor the effects of bone marrow stromal cell (BMSC) transplantation on neuronal integrity in infarct brain of rats. Methods-The BMSCs were harvested from green fluorescent protein-transgenic rats and were cultured. The rats were subjected to permanent middle cerebral artery occlusion. Their motor function was serially quantified throughout the experiments. The BMSCs or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 days after the insult. Using small-animal single photon emission computed tomography/computed tomography apparatus, the 123 I-IMZ uptake was serially measured at 6 and 35 days after the insult. Finally, fluorescence immunohistochemistry was performed to evaluate the distribution of engrafted cells and their phenotypes. Results-The distribution of 123 I-IMZ was markedly decreased in the ipsilateral neocortex at 6 days postischemia. The vehicle-transplanted animals did not show a significant change at 35 days postischemia. However, BMSC transplantation significantly improved the distribution of 123 I-IMZ in the peri-infarct neocortex as well as motor function. The engrafted BMSCs were densely distributed around cerebral infarct, and some of them expressed neuronal nuclear antigen and γ-aminobutyric acid type-A receptor. Conclusions-The present findings strongly suggest that the BMSCs may enhance functional recovery by improving the neuronal integrity in the peri-infarct area, when directly transplanted into the infarct brain at clinically relevant timing.

Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

“…These cells also have the capability to differentiate into GABAergic neuron-like cells when genetically engineered or treated with a cocktail conditioned medium [7, 10, 11]. Furthermore, previous studies have shown that GABAergic neuron-like cells derived from BMSCs express GABA and GABA A receptors following transplantation into the brain in a cerebral infarct model [16, 17]. These results have supported BMSCs as a potential source of GABA-synthesizing cells for grafting in neurological disorders.…”

Autologous Bone Marrow Mononuclear Cells Exert Broad Effects on Short- and Long-Term Biological and Functional Outcomes in Rodents with Intracerebral Hemorrhage

“…Various types of cells, including neural stem cells, embryonic stem cells, mesenchymal stem cells, and adipose stem cells, have been found to improve neurological outcome in animal stroke models [4][5][6][7]. Bone marrow-derived mononuclear cells (MNCs) are composed of diverse cell populations and are attractive as a cell therapy for the acute stage of stroke because they permit rapid bone marrow harvest and separation for autologous transplantation [8].…”

Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion

“…This procedure provides further hypoperfusion in the MCA territory by reducing collateral flow. The high reproducibility of focal cerebral infarction has been verified in this model (Fluri et al, 2015;Saito et al, 2013;Sugiyama et al, 2011).…”

“…The model used in the present study is known to produce focal cerebral infarction with high reproducibility (Fluri et al, 2015;Saito et al, 2013;Sugiyama et al, 2011), and is achieved through a combination of persistent antegrade hypoperfusion by direct MCAO and transient retrograde collateral hypoperfusion by bilateral common carotid artery occlusion (CCAO). Since leptomeningeal collateral flow in the rodent brain is well developed, direct MCAO only is not sufficient to ensure the induction of infarction.…”

“…The ischemic stroke model employed consisted of two surgical procedures: pMCAO by direct MCA ligation through craniotomy and tCHP by 1-hour bilateral CCAO (Saito et al, 2013;Sugiyama et al, 2011).…”