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Internal carotid artery (ICA) agenesis/aplasia is occasionally accompanied with cerebral aneurysms caused by hemodynamic stress. If the aneurysms are located around the circle of Willis, they are managed with clipping or coil embolization. Herein, we report a case of ICA agenesis with perforating artery aneurysms treated successfully with revascularization. Moreover, a literature review of ICA agenesis with cerebral aneurysms was performed to compare with the current case. We conducted a literature review using data from PubMed. A secondary search was also performed by reviewing the references of each article previously searched. In our case, the aneurysms shrank and disappeared after direct and indirect bypass surgeries, and indirect bypass developed as in moyamoya disease (MMD). The epidemiological and clinical features of aneurysms accompanied with ICA agenesis were identified via a literature review. Aneurysms with ICA agenesis categorized as type F based on the Lie classification system, or referred to as rete mirabile, are occasionally located in an untreatable site; hence, they cannot be treated with clipping or coil embolization. Moreover, results showed that previous studies did not use revascularization for the treatment of aneurysm. In conclusion, if an aneurysm with ICA agenesis is difficult to approach directly or via an endovascular procedure, revascularization can be a treatment option.

Background Monitoring of corticocortical evoked potentials (CCEPs) during brain tumor surgery of patients under anesthesia was recently reported to be effective in assisting in preservation of speech function. The aim of this study was to investigate whether CCEPs can be reproducibly measured between the frontal and temporal lobes during standard intracranial vascular surgery under general anesthesia; whether dynamic changes in CCEPs caused by reduced focal cerebral blood flow can be measured; and whether CCEPs can be used to monitor speech function, particularly associated with the left side of the brain. Methods We monitored CCEPs during 58 vascular surgeries (42 clipping procedures; 15 bypasses, 1 of which overlapped with clipping; and 2 hematoma removals from the left frontal and temporal lobe) at Kashiwaba Neurosurgical Hospital from October 2016 to January 2018. Results CCEPs could be reproducibly and routinely monitored in bilateral vascular surgeries. None of the patients experienced any postoperative symptoms or showed any ischemic lesions on postoperative magnetic resonance imaging; however, 5 patients temporarily demonstrated reduced CCEPs intraoperatively that were caused by transient obstructions of blood flow. Motor evoked potentials and somatosensory evoked potentials were simultaneously monitored intraoperatively and did not show any changes. Conclusions The results of our pilot study show that CCEPs can be routinely monitored during bilateral intracranial vascular surgery and that they are sensitive to ischemia. CCEPs on the left side could serve as unique intraoperative monitoring of speech function under anesthesia.

BackgroundOutcomes of endovascular treatment for acute ischemic stroke depend on the time interval from onset to reperfusion. Although the centralized ‘mothership’ method is considered preferable, the required transportation time increases the risk that a patient with a stroke may not receive intravenous or endovascular therapy. In contrast, ‘drive and retrieve’ describes a system wherein doctors from comprehensive stroke centers travel to primary stroke centers and provide endovascular treatment for acute ischemic stroke.ObjectiveTo describe the drive and retrieve system and verify the effects of this new collaboration on outcomes in patients with acute ischemic stroke among facilities.MethodsThis non-randomized, single-arm study retrospectively analyzed patients who met the inclusion criteria for endovascular treatment provided through a drive and retrieve system. Among the 122 patients treated by this system, we analyzed the time of onset to recanalization as the primary outcome. We also analyzed the efficacy of the drive and retrieve system using geographic information system analysis.ResultsThe median time from onset to recanalization was 229 min (IQR 170–307 min, 95% CI 201 to 252 min). The upper limit of the 95% CI for the time from onset to recanalization was shorter than the median times reported in two previous trials. Geographic information system analysis revealed an upward trend in the population coverage rate in each secondary medical area after the drive and retrieve method was introduced.ConclusionThe drive and retrieve method may be an effective form of cooperation between facilities located within 1 hour of a comprehensive stroke center.

Objective Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of cerebral infarct. However, it is still undetermined how the BMSCs should be transplanted to obtain the most efficient therapeutic benefits safely. The aim of this study was to assess whether a thermoreversible gelation polymer (TGP) hydrogel acts as a noninvasive, valuable scaffold in BMSC transplantation for infarct brain. Methods The mice were subjected to permanent middle cerebral artery occlusion. Vehicle, BMSC suspension, or the BMSC-TGP construct was transplanted onto the ipsilateral intact neocortex at 7 days after the insult. Neurological symptoms were assessed throughout the experiments. The fate of the transplanted BMSC was examined 8 weeks after transplantation with immunohistochemistry. Results TGP hydrogel completely disappeared and provoked no inflammation in the host brain. Many transplanted cells were widely engrafted in the ipsilateral cerebrum, including the dorsal neocortex adjacent to the cerebral infarct in the BMSC-TGP construct-treated mice. Their number was significantly larger than in the BMSC-treated mice. The majority were positive for both NeuN and MAP2 and morphologically simulated the neurons. Conclusion The findings suggest that surgical transplantation of tissue-engineered BMSCs onto the intact neocortex enhances the engraftment of donor cells around the cerebral infarct. These data may be useful in developing a noninvasive but efficient paradigm in neural tissue engineering. TGP hydrogel can be a promising candidate for valuable scaffolds in BMSC transplantation for central nervous system disorders because of its unique biochemical properties.

There are few studies that denote whether bone marrow stromal cells (BMSC) and bone marrow-derived mononuclear cells (MNC) show the same therapeutic effects, when directly transplanted into the infarct brain. This study therefore aimed to compare their biological properties and behaviors in the infarct brain. Mouse BMSC were harvested and cultured. Mouse MNC were obtained through centrifugation techniques. Their cell markers were analyzed with FACS analysis. The MNC (10(6) cells; n = 10) or BMSC (2 x 10(5) cells; n = 10) were stereotactically transplanted into the ipsilateral striatum of the mice subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their survival, migration, and differentiation in the infarct brain were precisely analyzed using immunohistochemistry 4 weeks after transplantation. The MNC were positive for CD34, CD45, CD90, but were negative for Sca-1. The BMSC were positive for CD90 and Sca-1. The transplanted BMSC, but not MNC, extensively migrated into the peri-infarct area. Approximately 20% of the transplanted BMSC expressed a neuronal marker, NeuN in the infarct brain, although only 1.4% of the transplanted MNC expressed NeuN. These findings strongly suggest that there are large, biological differences between MNC and BMSC as cell sources of regenerative medicine for ischemic stroke.

Transplanted bone marrow stromal cells (BMSC) promote functional recovery after spinal cord injury (SCI) through multiple mechanisms. A Rho kinase inhibitor, Fasudil also enhances axonal regeneration. This study was aimed to evaluate whether combination therapy of BMSC transplantation and Fasudil further enhances axonal regeneration and functional recovery in rats subjected to SCI. Fasudil or vehicle was injected for 2 weeks. BMSC or vehicle transplantation into the rostral site of SCI was performed at 7 days after injury. Neurological symptoms were assessed throughout the experiments. Fluoro-Ruby was injected into the dorsal funiculus of the rostral site of SCI at 63 days after injury. The fate of the transplanted BMSC was examined using immunohistochemistry. BMSC transplantation significantly increased the number of Fluoro-Ruby -labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI, enhancing functional recovery of the hind limbs. Some of the engrafted BMSC were positive for Fluoro-Ruby, neuronal specific nuclear protein and microtubule-associated protein-2, suggesting that they acquired neuronal phenotypes and built synaptic connection with the host's neural circuits. Fasudil treatment also improved axonal continuity, but did not promote functional recovery. Combination therapy dramatically increased the number of Fluoro-Ruby-labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI, but did not further boost the therapeutic effects on locomotor function by BMSC transplantation. The findings suggest that BMSC transplantation and Fasudil provide synergistic effects on axon regeneration after SCI, although further studies would be necessary to further enhance functional recovery.

Diffuse axonal injury (DAI) often leads to persistent cognitive dysfunction in spite of the lack of gross lesions on MRI. Therefore, this study was aimed to evaluate whether transplanted bone marrow stromal cells (BMSC) can improve DAI-induced cognitive dysfunction or not. The rats were subjected to impact acceleration head injury, using a pneumatic high-velocity impactor. The BMSC were harvested from the mice and were cultured. The BMSC (4.0 x 10(5) cells) or vehicle were stereotactically transplanted into the right striatum at 10 days post-injury. Cognitive function analysis was repeated at 1, 2, and 4 weeks post-injury, using the Morris water maze test. Histological analysis was performed at 2, 8 and 20 weeks post-injury, using double fluorescence immunohistochemistry. Transplanted BMSC were widely distributed in the injured brain and gradually acquired the phenotypes of neurons and astrocytes over 20 weeks. In addition, they significantly improved DAI-induced cognitive dysfunction as early as 2 weeks post-injury, although their processes of neuronal differentiation were not completed at this time point. The findings suggest that the engrafted BMSC may exhibit this early beneficial effect on cognitive function by producing neuroprotective or neurotrophic factors. In conclusion, direct transplantation of BMSC may serve as a novel therapeutic strategy to enhance the recovery from DAI-induced cognitive impairment.

OBJECTIVE: Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of spinal cord injury (SCl). However, it is still unclear how the transplanted BMSCs promote functional recovery after SCI. In this study, therefore, we evaluated how the transplanted BMSCs restore the function of the dorsal corticospinal tracts in the injured spinal cord. METHODS: The rats were subjected to incomplete SCI by means of a pneumatic impact device. BMSC or vehicle transplantation into the rostral site of SCl was performed at 7 days after injury. Neurological symptoms were assessed throughout the experiments. Fluoro-Ruby was injected into the dorsal funiculus of the rostral site of SCl at 63 days after injury. The fate of the transplanted BMSCs was examined using immunohistochemistry. RESULTS: BMSC transplantation significantly enhanced functional recovery of the hind limbs. The number of Fluoro-Ruby-labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI was significantly higher in the BMSC-transplanted animals than in the vehicle-transplanted animals. Some of the engrafted BMSCs were positive for Fluoro-Ruby, NeuN, and MAP2 in the gray matter, suggesting that they acquired neuronal phenotypes and built synaptic connection with the host's neural circuits. Others in the white matter morphologically simulated the astrocytes and were also positive for glial fibrillary acidic protein. CONCLUSION: The findings suggest that the transplanted BMSCs acquire neural cell phenotypes around the injury site and contribute to rebuild the neural circuits, including the corticospinal tract, promoting functional recovery of the hind limbs.

This study was aimed to assess whether ex vivo treatment with granulocyte-colony stimulating factor (G-CSF) modifies biological properties of bone marrow stromal cells (BMSC) and enhances functional recovery by BMSC transplantation into infarct brain. Immunohistochemistry was conducted to characterize the cultured BMSC. The pharmacological effects of G-CSF on their proliferation, cell cycle, and growth factor production were precisely analyzed, using FACS and ELISA techniques. Non-treated or G-CSF treated BMSC were stereotactically transplanted into the mice brain subjected to cerebral infarct, and its effects on functional and histological aspects were evaluated. The BMSC expressed the receptor for G-CSF. Treatment with 0.1muM of G-CSF significantly enhanced the proliferation of BMSC by increasing their population in S phase, and increased their production of SDF-1alpha, HGF, and NGF. When transplanted into infarct brain, G-CSF treated BMSC significantly improved motor function as early as 2 weeks after transplantation, whereas non-treated BMSC did 4 weeks after transplantation. These findings strongly suggest that G-CSF may enhance the proliferation and growth factor production of the cultured BMSC and accelerate functional restoration by BMSC transplantation. Such pharmacological "activation" of the BMSC may contribute to successful clinical application of BMSC transplantation therapy for ischemic stroke.

当院におけるt-PAを用いた超急性期虚血性脳血管障害の治療は2005年12月より開始され2007年2月まで計41例に施行してきた. 今回, 我々はそれまでにおける全症例の経過とその成績について様々な角度から検討を加え, t-PA療法の有効性や問題点に関し考察したので報告する. 当院では搬入後の効率化を図るためにプロトコールを基に進めているが, 発症よりrt-PA投与までの平均時間は約106分と早期に対処できていた. 治療成績は24時間後のNIHSSに関し34例で改善しており, 7例がprogressive strokeであった. 1カ月を経過した症例38例中35例で改善しているが, 3カ月後の時点では32例中28例で改善を示し, 非常に有効性が認められた. 2例が原疾患である脳梗塞にて死亡している. 合併症である脳出血は一例も認められなかったが, 皮下出血を3例に認められた. 経過中増悪した症例の原因は再塞栓, 主幹動脈の狭窄性病変, dementiaなどが挙げられた. 病態は塞栓症が19例, アテローマ血栓症が14例, ラクナ梗塞が6例であり, いずれも同様な改善傾向を示した. rt-PAによる脳梗塞の治療は病態に関わらず1カ月後, 3カ月後と改善が認められ有効であると考えられた.

BACKGROUND The posterior cerebral artery (PCA) is involved in approximately 30% of moyamoya disease (MMD) cases. However, there have been insufficient reports describing revascularization techniques in the posterior portion of the brain, particularly of direct anastomosis. OBJECTIVE To perform a technical assessment in patients with MMD who underwent either occipital artery (OA)-PCA bypass or OA-middle cerebral artery (MCA) bypass. METHODS A total of 428 revascularization procedures in 368 patients were retrospectively assessed by reviewing clinical charts and radiological data. RESULTS Ten patients (3.5%) were treated with direct bypass after the anterior revascularization with a median interval of 30 months (range, 5 months-16 years). Seven patients were

本研究は，TIAあるいは脳梗塞の既往を有しチクロピジン200 mg/dayを服用していた44例を対象に，薬剤をクロピドグレル75 mg/dayに変更した際の安全性，短期予後，血小板凝集能の変化などを前向きに検討した初めての報告である．薬剤の変更に伴う副作用や脳血管イベントの発生はなく，血液および生化学的検査データや，コラーゲンおよびADPによる血小板凝集能に有意な変化は認められなかった．

Background and Purpose Diffuse axonal injury (DAI) often leads to persistent cognitive dysfunction in spite of the lack of gross lesions on magnetic resonance (MR) imaging. Therefore, in this study, we aimed to develop a highly controlled and reproducible model of DAI that simulates post-traumatic cognitive dysfunction in humans; we aimed to investigate whether the intracerebral transplantation of bone marrow stromal cells (BMSCs) improved cognitive function in this model.

Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurologic function when transplanted into animal cerebral infarct models. However, it is still undetermined how the BMSCs should be transplanted to safely obtain the most efficient therapeutic benefits. Therefore, this study was carried out aiming to assess whether a thermoreversible gelation polymer (TGP) hydrogel would act as a noninvasive. valuable scaffold in BMSC transplantation for brain infarct. Mice were subjected to permanent middle cerebral artery occlusion. Vehicle, BMSC suspension, or a BMSC-TGP construct was transplanted onto the ipsilateral intact neocortex at 7 days after the insult. The TGP hydrogel completely disappeared and provoked no inflammation in the host brain. In the BMSC-TGP construct-treated mice, many transplanted cells were widely engrafted in the ipsilateral cerebrum, including the dorsal neocortex adjacent to the cerebral infarct. The number of these transplanted cells was significantly larger than that in the BMSC-treated mice; the majority of the cells were positive for both neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 (MAP2) and morphologically simulated neurons. These findings suggest that the surgical transplantation of tissue-engineered BMSCs onto the intact neocortex enhances the engraftment of donor cells around a cerebral infarct. TGP hydrogel, because of its unique biochemical properties, could be a promising candidate as a valuable scaffold in BMSC transplantation for central nervous system disorders.

Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of spinal cord injury (SCI). However, it is still unclear how the transplanted BMSCs promote functional recovery after SCI. In this study. therefore, we evaluated how transplanted BMSCs restore the function of the dorsal corticospinal tract (dCST) in the injured spinal cord. Rats were subjected to incomplete SCI, using a pneumatic impact device. Then BMSC suspension or vehicle was transplanted into the rostral site of the SCI at 7 days after the injury. Fluoro-ruby (FR; Molecular Probes), a fluorescent axonal tracer, was injected into the dorsal funiculus of the rostral site of the SCI 63 days after the injury. BMSC transplantation significantly enhanced functional recovery of the hind limbs. The number of FR-labeled fibers in the dCST at the caudal site of the SCI was significantly higher in the BMSC-transplanted animals than in the vehicle-transplanted animals. Some of the engrafted BMSCs were positive for FR, neuronal nuclear antigen (NeuN). and microtubule-associated protein 2 (MAP2) in the gray matter. The findings suggest that the transplanted BMSCs acquire neural cell phenotypes around the injury site and contribute to rebuilding neural circuits, including those in the CST. promoting functional recovery of the hind limbs.

Background and Purpose It is quite important to track donor cells transplanted into the central nervous system (CNS) in order to evaluate the therapeutic effects of cell transplantation therapy. Therefore, in this preliminary study we aimed to evaluate whether fluorescent quantum dots (QDs) would be useful in noninvasive cell tracking in cerebral infarcts of rats.

Diffuse axonal injury (DAI) plays a major role in the development of cognitive dysfunction, emotional difficulties and behavioral disturbances in patients following closed head injury, even when they have no definite abnormalities on conventional MRI. This study aimed to develop a highly controlled and reproducible model for DAI that simulates post-traumatic cognitive dysfunction in humans. Sprague-Dawley (SD) rats were subjected to impact acceleration head injury, using a pneumatic impact targeted to a steel disc centered onto their skull. The severity of injury was graded as three levels by adjusting the driving pressure at 60, 70 or 80 pounds per square inch. In vivo MRI was obtained 2 days post-injury. Cognitive function was evaluated using the Morris water maze at 1 and 2 weeks post-injury. HE staining and immunohistochemistry were performed to assess neuronal and axonal damages after 2 weeks. MRI demonstrated that this model induced no gross structural modification in the brain. The degree and duration of cognitive dysfunction were dependent on the force of impact. Histological analysis revealed the force-dependent damage of the neurons and microtubule-associated protein 2-positive axons in the neocortex. Hippocampal damage was much less pronounced and was not linked to cognitive dysfunction. This is the first report that precisely evaluates the threshold of impact energy to lead to neocortical damage and cognitive dysfunction in rodents. This model would be suitable for clarifying the complex mechanisms of post-traumatic brain damage and testing novel therapeutic approaches against post-traumatic cognitive dysfunction due to diffuse axonal damage.