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The article provides a laconic analysis of the prospects of using cellular technologies in the therapy of brain diseases. The authors compared different technologies of implantation of stem cells into the brain. The article focuses attention on implantation methods based on the natural migration of autologous stem cells to the brain along the cranial nerves.
Positive and negative aspects of cell technologies in
cerebral diseases
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System, SpineAssist, Renaissance Robotic Systems), assimilation
of high-tech operations (microsurgical, endovascular, stereotaxic
interventions etc.), implementation of combined therapy and new
rehabilitation techniques.4–6 Opportunities of diagnostic procedures
in cerebral diseases are also increased through modern diagnostic
equipment (MRI Scan, PET scan, SPECT scan, DWI MRI etc.), that
is able to enhance early-stage diagnostics, but still has no effect on
treatment outcomes.7–9 Current situation remains the basis for constant
search of new methods of treatment of cerebral diseases. And these
methods have been developed lately in the eld of cell biology and
In particular, cell technologies have been adapted to treatment of
socially important diseases in recent years.10 There were both followers
and opponents of cell technologies’ implementation into clinical
practice at the early stage, by the way that is usual for any novelty.
We will pay attention in terms of observed problem to methods based
on stem cells (SC) use in combined treatment of cerebral diseases. SC
has been found in various organs and systems of living organism and
their role is still not investigated in detail. Three main pools of SC
were detected in brain: in the area of olfactory bulbs, in hippocampus
and walls of brain ventricles.11 Potential of endogenous brain stem
cells in health and disease is constantly studied, but oppressive
statistics of chronic brain diseases and high mortality due to TBI,
stroke, inammatory and neurodestructive processes speaks for their
low effectiveness. There were experimental attempts performed
to increase potential of endogenous SC by additional injection of
exogenous SC by different ways into the area of pathological focus.
The amount of preliminarily in vitro cultivated exogenous stem
cells reached thousands and even millions per 1 ml. Three ways of
administration of SC suspension or mesenchymal SC (MSC) are
used in order to implement new method in cerebral diseases: into
bloodstream of arterial and venous vessels, into cerebrospinal uid
via lumbar or suboccipital puncture and nally directly into the area
of pathological focus in brain after additional craniotomy.12,13 Several
lacks have been stated at the experimental stage of all these ways of
SC administration. Administration of SC into bloodstream – besides
distribution in the whole volume of circulating blood – causes problems
at the stage of SC penetration through blood-brain barrier. Necessity of
additional surgical procedure – craniotomy – also becomes a negative
approach for seriously ill patient after stroke or TBI. Administration
of SC into cerebrospinal uid requires measures in order to overcome
craniospinal liquor ow and reach destructive area in brain (change of
body position, lumbar or suboccipital punctures). First experience of
cell technologies use also revealed one more negative effect coming
from the risk of SC transformation into tumor cells.14–16 Information
about malignancy processes usually appears after surgical procedures
in cosmetology rooms. However negative response in mass media
forms awareness in future patients.
Despite of pronounced side effects, cell technologies demonstrated
high effectiveness of reparative potential in cerebral diseases along
with minimum of side effects after application of autologous MSC on
the area of cranial nerves endings.17,18 Olfactory and trigeminal nerves
are the most common targets for application in the modelling of
brain diseases.17–19 For example, intranasal injection of FITC-labeled
MSC into the area of olfactory nerve endings resulted in appearance
of uorescent MSC already in 30 minutes in olfactory bulbs and in
several hours – in trauma region, mainly in anterior cranial fossa.18,19
Somatotropic distribution of stem cells in brain was substantiated by
the fact of predominant migration of MSC to destructed brain areas
located in posterior cranial fossa after preliminary administration
into the area of trigeminal nerve endings. Therefore, the technique
of MSC administration based on perineural migration of MSC to
neurodestructive region was experimentally developed for clinical
The next self-evident conclusion should be mentioned: it was
experimentally and clinically proved, that autologous stem cells are
the safest biomaterial for recovery of violated brain functions. The use
J Neurol Stroke. 2018;8(2):8788.
Volume 8 Issue 2 - 2018
Vladimir Kulchitsky, 1 Alexandra
Zamaro, 1 Yuri Shanko,2 Stanislav
1Institute of Physiology, National Academy of Sciences of
Belarus, Belarus
2Republican Centre of Neurology and Neurosurgery of
Ministry of Health, Belarus
3Liege University, Belgium
Correspondence: Vladimir Kulchitsky, Institute of Physiology,
National Academy of Sciences of Belarus, Address: 28
Akademicheskaya Street, Minsk, Belarus, Tel +375 17 2842458,
Email vladi@
Received: February 15, 2018 | Published: March 15, 2018
© 2018 Kulchitsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and build upon your work non-commercially.
Journal of Neurology & Stroke
Latter to Editor Open Access
Keywords: brain trauma; cell technology, diagnostic, intranasal
implantation, stem cell, stroke, therapy
Abbreviations: DWI, diffusion weighted imaging; FITC,
uorescein isothiocyanate; MRI, magnetic resonance imaging; MSC,
mesenchymal stem cells; PET, positron emission tomography; SC,
stem cells; SPECT, single photon emission computed tomography;
TBI, traumatic brain injury; WHO, world health organization
Discouraging statistics characterizes low efciency of diagnostics
and treatment of acute and chronic cerebrospinal diseases and
initiates search of new, more effective technologies to resolve that
socially important issue.1,2 About 6 million people die due to stroke
each year according to WHO.1 Traumatic Brain Injuries (TBI)
claim about 10 million lives annually.3 Surgical intervention still
remains the key method of treatment of such fatal cerebral diseases
as stroke, TBI, cerebral aneurysms and neoplasms. Efciency of
surgery increases with the use of robotic devices (da Vinci Robotic
Citation: Kulchitsky V, Zamaro A, Shanko Y, et al. Positive and negative aspects of cell technologies in cerebral diseases. J Neurol Stroke. 2018;8(2):87–88.
DOI: 10.15406/jnsk.2018.08.00286
Positive and negative aspects of cell technologies in cerebral diseases 88
©2018 Kulchitsky et al.
of autologous SC minimizes risk of tumor development associated
with administration of exogenous stem cells into living organism.
Experimenter and clinician should follow unbreakable principle “rst,
do no harm” in order to constantly achieve positive effects of clinical
technologies use and level negative effects.
This pooled analysis was funded by OOO Synergy.
Conict of interest
All listed authors concur with the submission of the manuscript; all
authors have approved the nal version. The authors have no nancial
or personal conicts of interest.
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and early outcome of stroke in Dublin, Ireland: the North Dublin
population stroke study. Stroke. 2012;43(8):2042–2047.
2. Feigin VL, Norrving B, Mensah GA. Global Burden of Stroke.
Circulation Research. 2017;120(3):439–448.
3. Nasser M, Bejjani F, Raad M, et al. Traumatic Brain Injury and
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Neurosurgery. 2014;24(3):305–311.
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8. Hojjati M, Badve C, Garg V, et al. Role of FDG-PET/MRI, FDG-
PET/CT, and Dynamic Susceptibility Contrast Perfusion MRI in
Differentiating Radiation Necrosis from Tumor Recurrence in
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cognitive impairment: a state-of-the-art review. BMC Medicine.
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cell therapy for major human neurological disorders. Stem Cell Rev.
11. Rueger MA, Androutsellis-Theotokis A. Identifying endogenous
neural stem cells in the adult brain in vitro and in vivo: novel
approaches. Curr Pharm Des. 2013;19(36):6499–6506.
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Nanosci Nanotechnol. 2014:14(1):976–982.
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of mesenchymal stromal cells for ischemic stroke. Neurology.
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a malignancy. Mol Ther. 2010;18 (7):1249–1250.
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... В физиологических условиях эндогенные стволовые клетки в этих областях мозга генерируют нейробласты, которые мигрируют к тем участкам мозга, где требуется интенсивное образование новых нейронных сетей [36]. Нами в экспериментах на грызунах установлено, что интраназальное введение МСК в остром периоде ишемии мозга сопровождалось более быстрым восстановлением контроля двигательной активности [37,38]. ...
... Травматические и ишемические повреждения мозга продолжают оставаться одной из сложнейших проблем современной медицины [5,46]. Изучение механизмов репаративных процессов в нервной тка-ни и разработка новых методов восстановления нейрональных структур составляют одно из актуальных направлений в физиологии и медицине и имеют большое значение для разработок новых терапевтических и реабилитационных стратегий [7,37,[47][48][49]. Ишемия мозга, которая фатально завершается ишемическим инсультом, часто возникает при нарушениях церебрального кровотока, что сопровождается недостаточным снабжением кислородом отделов мозга и развитием гипоксии разной степени выраженности [4,47]. ...
... На основании таких данных можно предлагать протокол терапии, акцентированный на усилении антиоксидантной системы. В настоящее время актуальным направлением является применение в регенеративной медицине стволовых клеток в качестве ведущего средства клеточной терапии [37,60]. Исследователей и клиницистов привлекают терапевтические свойства МСК [35,36,61], включая МСК мозга [36,62,63]. ...
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Introduction. With a decrease in the oxygen content in the inhaled air, violations of the cerebral blood flow, brain ischemia occurs, which can end in an ischemic stroke. Aim. Comparative analysis of the intensity of nitric oxide (NO) production and the copper content in the olfactory bulb tissues of the brain of male Wistar rats after modeling an ischemic stroke. Materials and methods. Modeling of ischemic stroke by ligation at the bifurcation level of both common carotid arteries and measuring the content of NO and copper by EPR spectroscopy. Results. The relative changes in the number of NO-containing complexes and the copper content were estimated from the integrated signal intensity of the complexes (DETC) 2 -Fe ²⁺ -NO and (DETC) 2 - Cu. A significant decrease by 47 % after 1 and 57 % after 2 days, respectively, in the NO content in the olfactory bulb of the rat brain was found after the ischemia modeling. The level of NO production in rats that underwent ischemia simulation with simultaneous intranasal administration of mesenchymal stem cells (MSCs) was also reduced by 51 % after 1 and 70 % after 2 days, respectively, after ischemia modeling. There was no significant difference in the NO content in the rats after ischemia modeling with simultaneous intranasal administration of MSCs compared to the ischemic rats. The copper content, which corresponds to the level of superoxide dismutase 1 and 3, in the rat’s olfactory bulb tended to increase after ischemia modeling and it persisted for two days of observation (an increase of 50 % in both cases). Intranasal administration of MSCs was accompanied by a significant increase in the Cu content (by 89 %) 1 day after the ischemia modeling, and 2 days later – by a decrease in its content by 36 % (compared to the control). In the control animals that were not subjected to surgical operations, no changes in the content of NO or copper were observed. Conclusion. The experiments showed a 2-fold decrease in the NO content in the olfactory bulb of the rat brain 1 and 2 days after the ischemia modeling, and demonstrated that the intranasal administration of MSCs did not affect the intensity of NO production on the 1st and 2nd days after the brain ischemia modeling, but was accompanied by an increase in the antioxidant protection of the nervous tissue one day after ischemia.
... Authors enthusiastically began experimental analysis of MSCs functions in the recovery of impaired brain functions [6][7][8][9][10]. ...
... Direct injection of MSCs into damaged brain region followed by trepanation is frequently unreasonable due to additional surgical interventions. Authors chose technique of MSCs perineural migration in combined therapy of brain injuries and strokes with SCs [6][7][8][9][10]. Cranial nerves were chosen as the way for MSCs migration. ...
... Cranial nerves were chosen as the way for MSCs migration. Injection of MSCs into cranial nerves' endings in facial area is quite simple surgical procedure which guarantees MSCs migration to damaged brain regions [6][7][8][9][10]. ...
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The article briefly describes advantages of autologous mesenchymal stem cells (MSCs) use in clinical conditions to correct structure and function of damaged areas in organs and tissues of humans and animals. The effectiveness of MSCs migration via per-ineural nerve spaces to inner organs was confirmed. Such method of cell therapy allows avoiding major surgeries and achieving more effective result in combination of classic treatment techniques with MSCs perineural delivery to damaged organs and tissues.
... Under physiological conditions, endogenous stem cells in these areas of the brain generate neuroblasts that migrate to those parts of the brain where an intensive formation of new neural networks is required [42]. The authors of the article in experiments on rodents found that intranasal administration of MSCs in the acute period of brain ischemia was accompanied by a faster restoration of the control of motor activity [36,43]. According to this, the aim of this work was to study the intensity of NO production and the presence of copper (as an indicator of superoxide dismutase) in the olfactory bulbs of the brain of the rat by EPR spectroscopy after modeling ischemic stroke of the brain, as well as the effect of intranasal administration of MSCs in the acute period after obstruction of the common carotid arteries. ...
... There is another aspect of the problem in addition to the above. Currently, the use of stem cells in regenerative medicine as a leading technique of cell therapy is a main trend [43,63]. Researchers and clinicians are attracted by the therapeutic properties of MSCs [41,64], including brain MSCs [42,65]. ...
Full-text available
A comparative experimental analysis by EPR spectroscopy of the intensity of nitric oxide (NO) production and the content of the copper in the tissues of olfactory bulb of the brain of male Wistar rats were performed after modeling of ischemic stroke and treatment with immediate intranasal injection of mesenchymal stem cells (MSCs). Brain ischemia was simulated by ligation at the level of bifurcation of the common carotid arteries. It was found a significant reduction of NO content in the olfactory bulb of the brain of rats on the 1st and 2nd days after modeling of ischemia. The level of NO production was also reduced on the 1st and 2nd days after ischemia with MSCs’ administration as compared to intact animals. It was not found the significant difference of the NO content in rats after ischemia with MSCs’ administration relative to ischemic rats. The copper content in the olfactory bulb of the rat, which corresponds to the level of superoxide dismutase 1 and 3, tended to increase after modeling ischemia and remained for 2 days. The MSCs’ administration was accompanied by a significant increase in copper content on the 1st day after modeling of ischemia and by decrease of its content on 2nd day after ischemia. The experiments showed that MSCs’ administration did not affect the intensity of NO production on the 1st and 2nd days after the modeling of brain ischemia, but was accompanied by an increase in the antioxidant protection of the nervous tissue 1 day after ischemia.
... The authors of the article focused on cellular technologies [3][4][5][6] as additional recovery measures in the early stages of the development and progression of brain diseases. In contrast to the popular systemic injections of stem cells (SCs), which are distributed via bloodstream throughout the body [3][4][5][6], emphasis is placed on the perineural migration of mesenchymal stem cells (MSCs) along the cranial nerves to the destruction site [7][8][9][10][11][12]. This tactic of targeted somatotopic distribution of autologous MSCs in those damaged areas of the brain, in which reparative processes are supposed to be activated, is aimed at improving the efficiency of classical therapy for patients with strokes and brain injuries [7,9,10,12]. ...
... In contrast to the popular systemic injections of stem cells (SCs), which are distributed via bloodstream throughout the body [3][4][5][6], emphasis is placed on the perineural migration of mesenchymal stem cells (MSCs) along the cranial nerves to the destruction site [7][8][9][10][11][12]. This tactic of targeted somatotopic distribution of autologous MSCs in those damaged areas of the brain, in which reparative processes are supposed to be activated, is aimed at improving the efficiency of classical therapy for patients with strokes and brain injuries [7,9,10,12]. It is noteworthy that the bioprinting technology pursues a similar goal when it is planned to implant a bioprinting substrate, including neural networks, into the damaged brain area [13]. ...
Full-text available
Bioprinting technologies and cell technologies are being developed to correct and / or restore the activity of various functional systems of the body. The paper focuses on the effective restoration of the functional unity of the nervous system and the whole body after injury. At the same time, the newly formed construction of reparation elements is radically different from the natural structures of the nervous tissue. The article draws attention to the unresolved methodological issues of bioprinting and cellular technologies, the main purpose of which is the most effective and correct recovery of damaged brain functions.
... One of the main problems in the use of MSCs is the limited understanding of how these cells "target" damaged tissues [7] and what specific neurotrophic factors contained in MSCs are responsible for the therapeutic mechanisms of action of MSCs [95]. It should be noted that there is objective evidence that MSCs exhibit immunosuppressive effects in inflammatory conditions [96,97]. Given that the secondary mechanisms of brain injury in TBI involve inflammatory response [98], the use of MSCs in treatment may cause unexpected effects [99]. ...
Full-text available
Relevance. The problem of effective prevention and treatment of traumatic brain injuries (TBI) of various etiologies has not been resolved in all countries of the world. Primary brain damage from trauma initiates secondary damage to the nervous tissue. As a result, the interaction of brain neural networks is disrupted and the control of somatic and visceral functions of the body is weakened. The article is based on our own clinical observations and comparison of results with literature data and provides discussion of the prospects for the use of cell technologies in prevention of fatal disorders of vital functions control in traumatic brain injuries. Objective. To evaluate effectiveness of intranasal perineural implantation of mesenchymal stem cells (MSCs) in the complex therapy of patients with TBI. Materials and methods. The technique intranasal perineural administration of MSCs was used in complex therapy of 15 patients with severe TBI. The patients were 19÷69 years old, 13 men and two women. A cell suspension was isolated from the adipose tissue of patient's abdominal wall and centrifuged for 10 min at 1500 rpm. The cell pellet was washed in phosphate buffered saline and DMEM. Cells were cultured in plastic culture flasks in humidified atmosphere with 5% CO2 content. The cell mass was trypsinized according to standard technique and resuspended in physiological saline on the day of implantation. Dynamics of culture growth, pluripotency, phenotyping of MSCs were monitored. MSCs were injected under general anesthesia into the submucosa of nasal cavity 3-4 times with an interval of 3-7 days, depending on the growth rate of MSCs, in a single dose from 12.0×106 to 35.0×106 cells. Results. The use of allogeneic and predominantly autologous MSCs of adipose tissue in the complex treatment of patients with severe TBI by intranasal perineural delivery to the area of traumatic brain injury does not cause complications and is a safe technique. 8 patients with severe TBI showed from 4 to 7 points according to the Glasgow Outcome Scale Extended, with an average of 5.4±1.1 points after 6 months. The main result is that complex therapy, including intranasal implantation of MSCs in acute and subacute periods of severe TBI, contributes to survival of patients and restoration of neurological-including cognitive-functions control. Conclusions. The effectiveness of intranasal perineural implantation of MSCs in the complex therapy of patients with TBI has been demonstrated. The mechanisms of the beneficial effects of perineural implantation of MSCs in patients with TBI require further research.
... The authors of the article are trying to uncover the mechanisms of the body's defense reactions against neoplasms. In this aspect, possibilities of cell therapy in the field of socially significant diseases are studied [5][6][7], including oncological pathology [8,9]. Other in vitro and in vivo experiments have also demonstrated that mesenchymal stem cells (MSCs) have reparative potential [10,11] and antitumor effects [12]. ...
Full-text available
Experiments were performed on 28 sexually mature Wistar rats divided into two equal groups. Rats were fixed in stereotactic apparatus and received 2.8×105 C6 glioma cells in 20 μl of F10 medium locally into frontal region of brain under ketamine-xylazine-acepromazine anesthesia. One group of rats (n=14) was implanted with 40×104 MSCs in 40 μl of low glucose DMEM medium into submucosa of nasal cavity. Further, only rats from this group received 40×104 mesenchymal stem cells (MSCs) intranasally in the form of a spray on a weekly basis. All 14 rats from the second group died within two months. Rats with implanted MSCs started to die in two and a half months. Two rats lived up to 8.5 months. One of these rats was decapitated, brain slices stained with hematoxylin-eosin and Nissl – and no tumor cells were found. A connective tissue scar was found at the site of injection.
... In addition, during the activation of the surface, free radicals are formed, and a chemically active surface layer is formed. In this paper, we studied the effects of CAPP on materials widely used in healthcare: medical steel (scalpels, clamps, dental instruments, etc.), glass (laboratory glass, dishes, etc.), polyamide material (surgical sutures, prostheses and orthopedic products, etc.), latex (medical gloves, etc.) [1,6,7]. Increasing the hydrophilicity of the surface of medical devices made of the materials under study will significantly improve their performance properties [8]. ...
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Paper summarizes results of cold c plasma use in medical devices surface treatment, focusing at manufacture applications. Attention is given to results of changes in the hydrophilic properties of glass surfaces, stainless steel, polyamide and latex when exposed to atmospheric plasma, depending on the time of treatment with cold plasma and distance to the surface. Abbreviations: Ar: Argon Gas; CAPP: Cold Atmospheric-Pressure Plasma; CM: Centimeter; MFC: Mass Flow Corrector
... Autologous MSCs from adipose tissue (6.0-8.010^6 cells) were used in complex postoperative treatment (submucous perineural implantation [18][19][20][21]). Migration of MSCs led to distinct progressive recovery of functions: bulbar disorders completely regressed in four months, hemiparesis disappeared, and motor coordination recovered. ...
Full-text available
34 cases of craniocervical junction region meningiomas are analyzed. It was about 1.6% of the general number of patients with primary symptomatic intracranial meningiomas. Lateral or anterolateral meningiomas were in 31 cases (91.2%), posterior – in 2 cases (5.9%), anterior without lateralization – in 1 case (2.9%). 27 patients (79.4%) are operated on through the suboccipital approach, 7 patients (20.6%) – through the far-lateral suboccipital (transcondyllar) approach. Total removal of tumors was made in 24 cases (70.6%), subtotal removal – in 6 cases (17.6%), partial removal – in 4 cases (11.8%). Mortality was not observed. Intraoperative monitoring significantly improved the preservation of neurological functions. There were no cases of tumors recidivating during a long-term observation. The suboccipital lateralized approach with laminectomy till the level of the lower pole of the tumor was sufficient to provide an adequate microsurgical removal of meningiomas of the craniocervical junction without resection of an atlantooccipital joint. The approach to the neoplasm matrix should be carried out after partial tumor resection without traction of brain stem parts. The use of intraoperative neuromonitoring supervised the stem functions at all stages of tumor removal and during the vertebral artery allocation.
... Autologous MSCs from adipose tissue (6.0-8.010^6 cells) were used in complex postoperative treatment (submucous perineural implantation [18][19][20][21]). Migration of MSCs led to distinct progressive recovery of functions: bulbar disorders completely regressed in four months, hemiparesis disappeared, and motor coordination recovered. ...
Full-text available
Citation: Shanko Y, Smeyanovich A, Ta-nin A, Sych E, Smeyanovich V, Bulgak U, Hubkin S, Zamaro A, Navitskaya V, Kulchitsky V. Contemporary Approach-es to Diagnostics and Treatment of Fo-ramen Magnum Meningiomas. Biomed J Sci & Tech Res 18(1)-2019. BJSTR. MS.ID.003081. DOI: 10.26717/BJSTR.2019.18.003081 34 cases of cranio cervical junction area meningiomas were analyzed. These can be found among 1.6% of the total number of patients with primary symptomatic intracrani-al meningiomas. Lateral or anterolateral tumor localization was observed in 31 (91.2%) cases, posterior – in 2 (5.9%), anterior without lateralization – in 1 (2.9%). 27 (79.4%) pa-tients underwent surgical intervention within suboccipital approach, 7 (20.6%) – postero-lateral suboccipital (transcondylar) approach. Total tumor resection was performed in 24 (70.6%) cases, subtotal – in 6 (17.6%) cases, partial – in 4 (11.8%). Postoperative mortal-ity and tumor recurrence were not observed during the whole observation period. Suboc-cipital lateral approach with laminectomy to the level of lower tumor pole was enough to provide adequate microsurgical craniovertebral meningioma resection without resection of atlanto-occipital articulation. The approach to neoplasm matrix was performed after tumor partial resection without brain stem traction. The use of intraoperative neuromon-itoring provided control of brain stem functions at all stages of tumor resection and ver-tebral artery isolation. Abbreviations: IX, X, XI: Cranial Nerves Designations; C2: Vertebra Designations; CT: Computed tomography; FM: Foramen Magnum; MRI: Magnetic Resonance Imaging; WHO: World Health Organization
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Abstract Introduction: Cell technologies represent a perspective direction due to activation of endogenous reparative processes. Correction of impaired brain functions using stem cells is one of the most effective methods in complex therapy of neurodestructive processes. Methods: Endoscopic perineural application of autologous mesenchymal stem cells (MSCs) as supplementary therapy in patients with stroke. Results: 42 patients (27-73 y.o.) received 3-4 intranasal submucosal applications (injections of autologous MSCs in 10 ml of suspension, ~12×106 cells per injection) with 5-9days interval. According to NIHSS, all patients demonstrated progressive relief of neurological symptoms. This pilot project was performed as per guideline developed by the authors (“The method of stroke treatment using autologous mesenchymal stem cells from adipose tissue”, No242-1218, the Ministry of Health of the Republic of Belarus, 2018). Conclusion: There were no cases of repeated stroke observed within the first year of observation. Keywords: stroke, mesenchymal stem cells, patient, perineural migration, somatotopic principle, treatment
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Background and purpose: To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). Methods: The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination. Additionally, 19 of 24 patients underwent PET/CT on the same day. Diagnosis was established by pathology in 17 of 24 and by clinical/radiologic consensus in 7 of 24. For the quantitative PET/MRI and PET/CT analysis, a region of interest (ROI) was drawn around each lesion and within the contralateral white matter. Lesion to contralateral white matter ratios for relative maximum, mean, and median were calculated. For pMRI, lesion ROI was drawn on the cerebral blood volume (CBV) maps and histogram metrics were calculated. Diagnostic performance for each metric was assessed using receiver operating characteristic curve analysis and area under curve (AUC) was calculated. Results: In 24 patients, 28 lesions were identified. For PET/MRI, relative mean ≥ 1.31 resulted in AUC of .94 with both sensitivity and negative predictive values (NPVs) of 100%. For pMRI, CBV max ≥3.32 yielded an AUC of .94 with both sensitivity and NPV measuring 100%. The joint model utilizing r-mean (PET/MRI) and CBV mode (pMRI) resulted in AUC of 1.0. Conclusion: Our study demonstrates that quantitative PET/MRI parameters in combination with DSC pMRI provide the best diagnostic utility in distinguishing RN from TR in treated GBMs.
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On the basis of the GBD (Global Burden of Disease) 2013 Study, this article provides an overview of the global, regional, and country-specific burden of stroke by sex and age groups, including trends in stroke burden from 1990 to 2013, and outlines recommended measures to reduce stroke burden. It shows that although stroke incidence, prevalence, mortality, and disability-adjusted life-years rates tend to decline from 1990 to 2013, the overall stroke burden in terms of absolute number of people affected by, or who remained disabled from, stroke has increased across the globe in both men and women of all ages. This provides a strong argument that "business as usual" for primary stroke prevention is not sufficiently effective. Although prevention of stroke is a complex medical and political issue, there is strong evidence that substantial prevention of stroke is feasible in practice. The need to scale-up the primary prevention actions is urgent.
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Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile – T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds. Diffusion MRI adds another dimension by showing graded damage to white matter, making it more sensitive to white matter injury than FLAIR. Regions of neuroinflammatory disruption of the blood–brain barrier with increased permeability can be quantified and visualized with dynamic contrast-enhanced MRI. PET shows metabolism of glucose and accumulation of amyloid and tau, which is useful in showing abnormal metabolism in Alzheimer’s disease. Combining MRI and PET allows identification of patients with mixed dementia, with MRI showing white matter injury and PET demonstrating regional impairment of glucose metabolism and deposition of amyloid. Excellent anatomical detail can be observed with 7.0-Tesla MRI. Imaging is the optimal method to follow the effect of treatments since changes in MRI scans are seen prior to those in cognition. This review describes the role of various imaging modalities in the diagnosis and treatment of vascular cognitive impairment.
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Traumatic brain injury, often referred to as the "silent epidemic," is a non-degenerative, non-congenital insult to the brain due to a blow or penetrating object that disrupts the function of the brain leading to permanent or temporary impairment of cognition, physical and psychosocial functions. Traumatic brain injury usually has poor prognosis for long-term treatment and is a major cause of mortality and morbidity worldwide; approximately 10 million deaths and/or hospitalizations annually are directly related to traumatic brain injury. Traumatic brain injury involves primary and secondary insults. Primary injury occurs during the initial insult, and results from direct or indirect force applied to the physical structures of the brain. Secondary injury is characterized by longer-term degeneration of neurons, glial cells, and vascular tissues due to activation of several proteases, glutamate and pro-inflammatory cytokine secretion. In addition, there is growing evidence that the blood-brain barrier is involved in the course of traumatic brain injury pathophysiology and has detrimental effects on the overall pathology of brain trauma, as will be discussed in this work.
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There is a paucity of accurate and reliable biomarkers to detect traumatic brain injury, grade its severity, and model post-traumatic brain injury (TBI) recovery. This gap could be addressed via advances in brain mapping which define injury signatures and enable tracking of post-injury trajectories at the individual level. Mapping of molecular and anatomical changes and of modifications in functional activation supports the conceptual paradigm of TBI as a disorder of large-scale neural connectivity. Imaging approaches with particular relevance are magnetic resonance techniques (diffusion weighted imaging, diffusion tensor imaging, susceptibility weighted imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, and positron emission tomographic methods including molecular neuroimaging). Inferences from mapping represent unique endophenotypes which have the potential to transform classification and treatment of patients with TBI. Limitations of these methods, as well as future research directions, are highlighted.
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Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI) mouse model. In this study, we investigated the potential of human MSCs (hMSCs) to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×106 or 2×106 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC) was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×106 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.
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Neurosurgery is one of the most demanding surgical specialties in terms of precision requirements and surgical field limitations. Recent advancements in robotic technology have generated the possibility of incorporating advanced technological tools to the neurosurgical operating room. Although previous studies have addressed the specific details of new robotic systems, there is very little literature on the strengths and drawbacks of past attempts, currently available platforms and prototypes in development. In this review, the authors present a critical historical analysis of the development of robotic technology in neurosurgery as well as a comprehensive summary of the currently available systems that can be expected to be incorporated to the neurosurgical armamentarium in the near future. Finally, the authors present a critical analysis of the main technical challenges in robotic technology development at the present time (such as the design of improved systems for haptic feedback and the necessity of incorporating intraoperative imaging data) as well as the benefits which robotic technology is expected to bring to specific neurosurgical subspecialties in the near future.
Over the last decade, surgical technology in planning, mapping, optics, robotics, devices, and minimally invasive techniques has changed the face of modern neurosurgery. We explore the current advances in clinical technology across all neurosurgical subspecialties, examine how clinical practice is being shaped by this technology, and suggest what the operating room of tomorrow may look like.
From the outset, it was apparent that developing new therapies with mesenchymal stem/stromal cells (MSCs) was not a simple or easy task. Among the earliest experiments was administration of MSCs from normal mice to transgenic mice that developed brittle bones because they expressed a mutated gene for type 1 collagen isolated from a patient with osteogenesis imperfecta. The results prompted a clinical trial of MSCs in patients with severe osteogenesis imperfecta. Subsequent work by large numbers of scientists and clinicians has established that, with minor exceptions, MSCs do not engraft or differentiate to a large extent in vivo. Instead the cells produce beneficial effects in a large number of animal models and some clinical trials by secreting paracrine factors and extracellular vesicles in a “hit and run” scenario. The field faces a number of challenges, but the results indicate that we are on the way to effective therapies for millions of patients who suffer from devastating diseases.
This paper reviews the recent studies and development of stem cell therapy for ischemic stroke. Stem cells can differentiate into several types of mature cells, including neurons and glial cells. Stem cell transplantation, a promising therapy, can be able to facilitate functional recovery both in animal models and stroke patients. In this review, we introduce briefly the different types of endogenous stem cells and the transplantation of exogenous stem cells; in addition, we discuss the timing, dosage, route, and tracing of stem cell therapy for ischemic stroke in details. Finally, the clinical challenge and application of stem cells in future are also discussed.