Background and Purpose— Multilineage-differentiating stress-enduring cells are endogenous nontumorigenic reparative pluripotent-like stem cells found in bone marrow, peripheral blood, and connective tissues. Topically administered human multilineage-differentiating stress-enduring cells into rat/mouse stroke models differentiated into neural cells and promoted clinically relevant functional recovery. However, critical questions on the appropriate timing and dose, and safety of the less invasive intravenous administration of clinical-grade multilineage-differentiating stress-enduring cell–based product CL2020 remain unanswered. Methods— Using an immunodeficient mouse lacunar model, CL2020 was administered via the cervical vein in different doses (high dose=5×10 4 cells/body; medium dose=1×10 4 cells/body; low dose=5×10 3 cells/body) at subacute phase (≈9 days after onset) and chronic phase (≈30 days). Cylinder test, depletion of human cells by diphtheria toxin administration, immunohistochemistry, and human specific-genome detection were performed. Results— Tumorigenesis and adverse effects were not detected for up to 22 weeks. The high-dose group displayed significant functional recovery compared with the vehicle group in cylinder test in subacute-phase–treated and chronic-phase–treated animals after 6 weeks and 8 weeks post-injection, respectively. In the high-dose group of subacute-phase–treated animals, robust and stable recovery in cylinder test persisted up to 22 weeks compared with the vehicle group. In both groups, intraperitoneal injection of diphtheria toxin abrogated the functional recovery. Anti-human mitochondria revealed CL2020 distributed mainly in the peri-infarct area at 1, 10, and 22 weeks and expressed NeuN (neuronal nuclei)- and MAP-2 (microtubule-associated protein-2)-immunoreactivity. Conclusions— Intravenously administered CL2020 was safe, migrated to the peri-infarct area, and afforded functional recovery in experimental stroke.
This report presents a case of stroke-like migraine attacks after radiation therapy (SMART) syndrome in a 31-year-old man in whom symptoms and radiological findings resolved with steroid pulsed therapy and reviews the literatures with special emphasis on the use of steroids against SMART syndrome. The patient had a past history of left temporal anaplastic astrocytoma and was treated with surgery followed by local 72 Gy radiation therapy and chemotherapy using Nimustine Hydrochloride. Four years after the surgery, he was suffering from subacute progressing symptoms of headache, right hemianopia, right hemiparesis and aphasia from 2 to 4 days before admission to our hospital. At first he was diagnosed as symptomatic epilepsy but after extensive examination, the final diagnosis was SMART syndrome. His symptoms soon improved with steroid pulse therapy. In the literature, steroid pulse therapy is not necessarily a standard of care for SMART syndrome, but it seemed to decrease the need of biopsy. As the lesions of SMART syndrome require differential diagnosis from recurrences, biopsy was performed in some cases. However, lack of benefit and possible detriment is reported with biopsy of SMART lesions. Through this experience we suggest that steroid pulse therapy may provide speedy recovery from symptoms, and it should be considered before other invasive investigations or treatments.
Some cases of aneurysms originating from the fenestrated A1 segment of the anterior cerebral artery (ACA) have been reported, but the pitfalls of the surgical procedure have not been well determined. We herein report 2 cases of a saccular aneurysm arising from the fenestrated A1 segment. Case 1 was a 72-year-old man incidentally diagnosed with an unruptured left ACA aneurysm on magnetic resonance imaging (MRI). Cerebral angiography revealed a saccular aneurysm arising from the proximal end of the left A1 segment. He underwent surgical clipping via the left pterional approach. The aneurysm originated from the proximal bifurcation of the fenestrated left A1 segment. A fenestrated ring clip was applied to obliterate the aneurysmal neck and one small fenestrated trunk, preserving the other fenestrated trunk and perforators around the fenestration. Case 2 was a 73-year-old man incidentally diagnosed with an unruptured ACA aneurysm on MRI. Cerebral angiography revealed a saccular aneurysm arising from the proximal end of the fenestrated left A1 segment. He underwent surgical clipping via the interhemispheric approach. The aneurysm originated from the proximal bifurcation of the fenestrated left A1 segment. A fenestrated ring clip was applied to obliterate the aneurysmal neck and one hypoplastic fenestrated trunk, preserving the other fenestrated trunk and perforators around the aneurysm. Detailed intraoperative evaluations of the anatomical structure and hemodynamics around the fenestration are important. The intentional obliteration of a fenestrated trunk and application of fenestrated clips need to be considered in difficult cases in order to expose the aneurysmal neck.
OBJECTIVEMultilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells, which can be harvested from the bone marrow. After transplantation, Muse cells can migrate to an injured site of the body and exert repair effects. However, it remains unknown whether Muse cell transplantation can be an effective treatment in spinal cord injury (SCI).METHODSThe authors used a rat model of thoracic spinal cord contusion injury. For Muse cell transplantation, the clinical product CL2020 containing 300,000 Muse cells was administered intravenously 1 day after midthoracic SCI. Animals were divided into CL2020 (n = 11) and vehicle-treated (n = 15) groups. Behavioral and histological evaluations were conducted over a period of 8 weeks to see whether intravenous CL2020 administration provided therapeutic effects for SCI. The effects of human-selective diphtheria toxin on reversion of the therapeutic effects of CL2020 were also investigated.RESULTSHindlimb motor function significantly improved after CL2020 transplantations. Importantly, the effects were reverted by the human-selective diphtheria toxin. In immunohistochemical analyses, the cystic cavity formed after the injury was smaller in the CL2020 group. Furthermore, higher numbers of descending 5-hydroxytryptamine (5-HT) fibers were preserved distal to the injury site after CL2020 administration. Eight weeks after the injury, Muse cells in CL2020 were confirmed to differentiate most predominantly into neuronal cells in the injured spinal cord.CONCLUSIONSFollowing SCI, Muse cells in CL2020 can reach the injured spinal cord after intravenous administration and differentiate into neuronal cells. Muse cells in CL2020 facilitated nerve fiber preservation and exerted therapeutic potential for severe SCI.
Intraoperative fluorescence angiography (IFA) using the fluorescent dyes fluorescein (FS) or indocyanine green (ICG) is a useful tool for cerebrovascular surgery. We compared these two fluorescent dyes for the detection of perforators and their application during bypass surgery. Methods: Intraoperative fluorescence angiography was performed with intraoperative observatory modules using a OPMI PENTERO 900 microscope including two types of induction light for both FS and ICG to evaluate each dye within the same fluorescent operative field. Each dye (250 mg FS and 10× diluted ICG) were intravenously administered and quantitative analysis was performed within regions of interest using movie analysis software. The subjects for the evaluation of perforators were 17 cases of cerebral aneurysms treated in our department from December 2015 to May 2016.
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