Development and Validation of a Brain Phantom for Therapeutic Cooling Devices

2017 ◽  
Vol 139 (5) ◽  
Author(s):  
Ryan D. M. Packett ◽  
Philip J. Brown ◽  
Gautam S. S. Popli ◽  
F. Scott Gayzik
Keyword(s):  
Thermal Response ◽  
Brain Parenchyma ◽  
Brain Response ◽  
Long Term Outcomes ◽  
Development And Validation ◽  
The Brain ◽  
Brain Phantom ◽  
Multiple Conditions ◽  
Good Agreement

Tissue cooling has been proven as a viable therapy for multiple conditions and injuries and has been applied to the brain to treat epilepsy and concussions, leading to improved long-term outcomes. To facilitate the study of temperature reduction as a function of various cooling methods, a thermal brain phantom was developed and analyzed. The phantom is composed of a potassium-neutralized, superabsorbent copolymer hydrogel. The phantom was tested in a series of cooling trials using a cooling block and 37 deg water representing nondirectional blood flow ranging up to 6 gph, a physiologically representative range based on the prototype volume. Results were compared against a validated finite difference (FD) model. Two sets of parameters were used in the FD model: one set to represent the phantom itself and a second set to represent brain parenchyma. The model was then used to calculate steady-state cooling at a depth of 5 mm for all flow rates, for both the phantom and a model of the brain. This effort was undertaken to (1) validate the FD model against the phantom results and (2) evaluate how similar the thermal response of the phantom is to that of a perfused brain. The FD phantom model showed good agreement with the empirical phantom results. Furthermore, the empirical phantom agreed with the predicted brain response within 3.5% at physiological flow, suggesting a biofidelic thermal response. The phantom will be used as a platform for future studies of thermally mediated therapies applied to the cerebral cortex.

Visualization of immature brain lesions: MR patterns of long-term outcomes. Case reports

2021 ◽  
Vol 2 (2) ◽  
pp. 94-99
Author(s):  
Anatoly V. Anikin ◽  
Milana A. Basargina ◽  
Eugeniya V. Uvakina
Keyword(s):  
White Matter ◽  
Premature Infants ◽  
Periventricular Leukomalacia ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Lesions ◽  
Gestation Period ◽  
Long Term Outcomes ◽  
Immature Brain ◽  
The Brain

The periventricular and deep white matter of the immature brain of premature infants has an increased vulnerability to various, primarily ischemic injuries. The leading mechanism of selective vulnerability of the white matter of the large hemispheres in children with a low gestation period is the lack of formation of adjacent blood circulation zones between the main arteries of the developing brain. Magnetic resonance imaging has a high sensitivity to detect damage to the brain substance, both in the acute period and in the period of long-term outcomes. Periventricular leukomalacia (PVL) is one of the variants of brain damage in premature infants and the most common term in the conclusions of diagnostic doctors (ultrasound, CT, MRI). Considering the pathomorphological criteria, not always detected changes in the white matter of the large hemispheres are PVL. Diffuse (telencephalic) gliosis and diffuse leukomalacia are ordinary and typical variants of damage to the white matter of the large hemispheres in extremely premature infants, with a gestation period of up to 30-32 weeks. In the first variant, atrophic changes predominate with a pronounced decrease in the volume of white matter and a secondary expansion of the lateral ventricles. Diffuse leukomalacia is most often mistaken for PVL, but the localization of the white matter lesion of the large hemispheres is extensive and extends beyond the peri- and paraventricular region. Clinical examples show various variants of primary non-hemorrhagic brain lesions in prematurely born children in the long-term period. The analysis of the revealed changes is carried out, taking into account current data on developing the brain and pathomorphological criteria.

Glycogen: Multiple Roles in the CNS

2016 ◽  
Vol 23 (4) ◽  
pp. 356-363 ◽  
Author(s):  
Laura Rich ◽  
Angus M. Brown
Keyword(s):  
Glycogen Metabolism ◽  
Prenatal Development ◽  
Brain Parenchyma ◽  
Multiple Roles ◽  
Primary Role ◽  
Neuronal Function ◽  
Brain Functions ◽  
Continuous Support ◽  
The Brain

The historically neurocentric view of astrocytes as Styrofoam cushioning that rigidly clad neurons within the brain parenchyma has been superseded in the past 30 years by an increasing appreciation of the myriad roles astrocytes contribute to supporting physiological brain function. It is widely recognized that the continuous support provided by astrocytes, from prenatal development to maturity, is vital for neuronal function. Indeed, the numerous and diverse roles furnished by astrocytes contrasts with the vital but restricted transmission of action potentials that is the neuron’s primary role. An emerging role for astrocytes is that of providing energy substrate in the form of glycogen-derived lactate to neurons. This role was established during periods of limited glucose availability but has been extended to encompass one of the most important physiological brain functions, learning and memory. In this context glycogen metabolism is integral to the consolidation of learning into long-term retention of memories, a process vital to the higher functioning of the human brain.

scholarly journals Clinical Management of Moyamoya Patients

2021 ◽  
Vol 10 (16) ◽  
pp. 3628
Author(s):  
Isabella Canavero ◽  
Ignazio Gaspare Vetrano ◽  
Marialuisa Zedde ◽  
Rosario Pascarella ◽  
Laura Gatti ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Long Term Outcomes ◽  
Hemorrhagic Risk ◽  
Collateral Vessels ◽  
Hereditary Conditions ◽  
The Brain ◽  
Internal Carotid Arteries

Moyamoya angiopathy (MMA) is a peculiar cerebrovascular condition characterized by progressive steno-occlusion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the development of a network of fragile collateral vessels at the base of the brain. The diagnosis is essentially made by radiological angiographic techniques. MMA is often idiopathic (moyamoya disease-MMD); conversely, it can be associated with acquired or hereditary conditions (moyamoya Syndrome-MMS); however, the pathophysiology underlying either MMD or MMS has not been fully elucidated to date, and this poor knowledge reflects uncertainties and heterogeneity in patient management. MMD and MMS also have similar clinical expressions, including, above all, ischemic and hemorrhagic strokes, then headaches, seizures, cognitive impairment, and movement disorders. The available treatment strategies are currently shared between idiopathic MMD and MMS, including pharmacological and surgical stroke prevention treatments and symptomatic drugs. No pharmacological treatment able to reverse the progressive disappearance of the ICAs has been found to date in both idiopathic and syndromic cases. Antithrombotic agents are usually prescribed in ischemic MMA, although the coexisting hemorrhagic risk should be considered. Surgical revascularization techniques, which are currently the best available treatment in symptomatic MMA, are associated with good long-term outcomes and reduced ischemic and hemorrhagic risks. Given the lack of dedicated randomized clinical trials, current treatment is mainly based on observational studies and physicians’ and surgeons’ expertise.

Treatment Model of CNS Lymphoma Using Complement-Dependent Cytotoxicity Induced by Rituximab and Autoserum.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3739-3739
Author(s):  
Yasuyuki Miyake ◽  
Yasushi Okoshi ◽  
Takayuki Machino ◽  
Shigeru Chiba
Keyword(s):  
Lateral Ventricle ◽  
Raji Cell ◽  
Technical Problem ◽  
Brain Parenchyma ◽  
Autologous Serum ◽  
Ependymal Cells ◽  
Treatment Model ◽  
Complement Dependent Cytotoxicity ◽  
The Brain

Abstract Abstract 3739 Poster Board III-675 Background Primary central nervous system lymphoma (PCNSL) is almost exclusively CD20-positive non-Hodgkin lymphoma (NHL). Although rituximab (R) is widely used for CD20-positive NHL, it is not considered to reach brain lesions effectively beyond the blood brain barrier. Intraventricule administration (ivt) of R is reported to be effective in meningeal lymphoma but the effect on lesions in the brain parenchyma seems to be limited. Recently, a case of refractory PCNSL that was successfully treated with ivt of R with autologous serum was reported (Takami A, et al. Cancer Science, 2006). Because the cerebrospinal fluid does not contain complements which exists in the serum, induction of complement-dependent cytotoxicity by ivt of R plus autoserum was speculated. To investigate this effect, we developed an animal treatment model of CNSL. Materials and methods Raji, CD20-positive Burkitt lymphoma cell line, was inoculated into the deep frontal lobe of the brain of 8-week old F344 (nru-/nru-) nude rats, using brain stereotaxic apparatus. At the same time, a cannula was placed into the ipsilateral lateral ventricle. After several days, R or control immunoglobulin (cIg), plus human serum or saline, was administrated into the lateral ventricle. Results The brain was extracted 24 hours after the last administration and frozen section was made. Human CD20-positive Raji cell tumor was also positively stained with FITC-conjugated anti-human IgG antibody when R but not cIg was administrated. Consequently, R in the lateral ventricle was considered to penetrate ependymal cells and brain parenchyma, and bound to lymphoma cells. Next, these rats were treated with ivt of R plus serum (R + Serum), cIg plus serum (cIg + Serum), or R plus saline (R + saline). These were administrated once a day from day 5 to day 9 after inoculation of Raji, and then survival was monitored. When an obvious weakness, such as marked and consecutively loss of activity or weight, was observed, these rats were euthanized and this is defined as dead day. In each case, the brain was extirpated and examined whether lymphoma existed or not. Death without lymphoma or from technical problem was excluded from the analysis. Survival of each group was analyzed by Kaplan-Meier method and log-lank test. R + Serum group had longer survival than cIg + Serum (p = 0.049). Long-term survivors were only seen in R + Serum and this group seemed to be superior to R + saline but statistical difference was not detected (p = 0.083). There were no difference between cIg + Serum and R + saline (p =0.382) and neither group had long-term survivor. Conclusion The possibility of novel treatment of CNSL with ivt of R and autoserum was shown in the rat CNSL model. To confirm this approach, clinical trials are warranted. Disclosures: No relevant conflicts of interest to declare.

‘Alzheimer-like’ pathology in a murine model of arterial hypertension

2011 ◽  
Vol 39 (4) ◽  
pp. 939-944 ◽  
Author(s):  
Daniela Carnevale ◽  
Giuseppe Lembo
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Strong Association ◽  
Epidemiological Studies ◽  
Brain Parenchyma ◽  
Murine Models ◽  
Ad Alzheimer’S Disease ◽  
The Brain

Genetic AD (Alzheimer's disease) accounts for only few AD cases and is almost exclusively associated with increased amyloid production in the brain. Instead, most patients are affected with the sporadic form of AD and typically have altered clearance mechanisms. The identification of factors that influence the onset and progression of sporadic AD is a key step towards understanding its mechanism(s) and developing successful therapies. An increasing number of epidemiological studies describe a strong association between AD and cardiovascular risk factors, particularly hypertension, that exerts detrimental effects on the cerebral circulation, favouring chronic brain hypoperfusion. However, a clear demonstration of a pathophysiological link between cardiovascular risk factors and AD aetiology is still missing. To increase our knowledge of the mechanisms involved in the brain's response to hypertension and their possible role in promoting amyloid deposition in the brain, we have performed and investigated in depth different murine models of hypertension, induced either pharmacologically or mechanically, leading in the long term to plaque formation in the brain parenchyma and around blood vessels. In the present paper, we review the major findings in this particular experimental setting that allow us to study the pathogenetic mechanisms of sporadic AD triggered by vascular risk factors.

scholarly journals An argument for broad use of high efficacy treatments in early multiple sclerosis

2019 ◽  
Vol 7 (1) ◽  
pp. e636 ◽  
Author(s):  
James M. Stankiewicz ◽  
Howard L. Weiner
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Approach ◽  
Disease Course ◽  
Long Term Outcomes ◽  
The Past ◽  
Recent Developments ◽  
The Brain

Two different treatment paradigms are most often used in multiple sclerosis (MS). An escalation or induction approach is considered when treating a patient early in the disease course. An escalator prioritizes safety, whereas an inducer would favor efficacy. Our understanding of MS pathophysiology has evolved with novel in vivo and in vitro observations. The treatment landscape has also shifted significantly with the approval of over 10 new medications over the past decade alone. Here, we re-examine the treatment approach in light of these recent developments. We believe that recent work suggests that early prediction of the disease course is fraught, the amount of damage to the brain that MS causes is underappreciated, and its impact on patient function oftentimes is underestimated. These concerns, coupled with the recent availability of agents that allow a better therapeutic effect without compromising safety, lead us to believe that initiating higher efficacy treatments early is the best way to achieve the best possible long-term outcomes for people with MS.

scholarly journals Effects of long-term and brain-wide colonization of peripheral bone-marrow derived myeloid cells in the CNS

2020 ◽  
Author(s):  
Lindsay A. Hohsfield ◽  
Allison R. Najafi ◽  
Yasamine Ghorbanian ◽  
Neelakshi Soni ◽  
Edna E. Hingco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Cells ◽  
Marrow Transplant ◽  
Brain Parenchyma ◽  
Immune Defense ◽  
Whole Body ◽  
Long Term Effects ◽  
The Brain ◽  
Peripheral Bone

Abstract Background Microglia, the primary resident myeloid cells of brain, play critical roles in immune defense by maintaining tissue homeostasis and responding to injury or disease. However, microglial activation and dysfunction has been implicated in a number of central nervous system (CNS) disorders, thus developing tools to manipulate and replace these myeloid cells in CNS is of therapeutic interest. Methods Using whole body irradiation, bone marrow transplant, and colony-stimulating factor 1 receptor inhibition, we achieve long-term and brain-wide (~ 80%) engraftment and colonization of peripheral bone marrow-derived myeloid cells (i.e. monocytes) in the brain parenchyma and evaluated the long-term effects of their colonization in the CNS. Results Here, we identify a monocyte signature that includes an upregulation in Ccr1, Ms4a6b, Ms4a6c, Ms4a7, Apobec1, Lyz2, Mrc1, Tmem221, Tlr8, Lilrb4a, Msr1, Nnt, and Wdfy1, and a downregulation of Siglech, Slc2a5, and Ccl21a/b. We demonstrate that irradiation and long-term (~ 6 months) engraftment of the CNS by monocytes induces brain-region dependent alterations in transcription profiles, astrocytes, neuronal structures, including synaptic components, and cognition. Although our results show that microglial replacement with peripheral derived myeloid cells is feasible and that irradiation-induced changes can be reversed by the replacement of microglia with monocytes in the hippocampus, we also observe that brain-wide engraftment of peripheral myeloid cells (relying on irradiation) can result in cognitive and synaptic deficits. Conclusions These findings provide insight into better understanding the role and complexity of myeloid cells in the brain, including their regulation of other CNS cells and functional outcomes.

scholarly journals A Rat Model of Prenatal Zika Virus Infection and Associated Long-Term Outcomes

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2298
Author(s):  
Morgan L. Sherer ◽  
Elise A. Lemanski ◽  
Rita T. Patel ◽  
Shannon R. Wheeler ◽  
Mark S. Parcells ◽  
...  
Keyword(s):  
Rat Model ◽  
Zika Virus ◽  
Fold Increase ◽  
Interferon Response ◽  
Motor Deficits ◽  
Long Term Outcomes ◽  
Zikv Infection ◽  
Full Spectrum ◽  
The Brain

Zika virus (ZIKV) is a mosquito-borne flavivirus that became widely recognized due to the epidemic in Brazil in 2015. Since then, there has been nearly a 20-fold increase in the incidence of microcephaly and birth defects seen among women giving birth in Brazil, leading the Centers for Disease Control and Prevention (CDC) to officially declare a causal link between prenatal ZIKV infection and the serious brain abnormalities seen in affected infants. Here, we used a unique rat model of prenatal ZIKV infection to study three possible long-term outcomes of congenital ZIKV infection: (1) behavior, (2) cell proliferation, survival, and differentiation in the brain, and (3) immune responses later in life. Adult offspring that were prenatally infected with ZIKV exhibited motor deficits in a sex-specific manner, and failed to mount a normal interferon response to a viral immune challenge later in life. Despite undetectable levels of ZIKV in the brain and serum in these offspring at P2, P24, or P60, these results suggest that prenatal exposure to ZIKV results in lasting consequences that could significantly impact the health of the offspring. To help individuals already exposed to ZIKV, as well as be prepared for future outbreaks, we need to understand the full spectrum of neurological and immunological consequences that could arise following prenatal ZIKV infection.

scholarly journals The self’s choice: Priming attentional focus on bodily self promotes loss frequency bias

2021 ◽  
Author(s):  
Valeria Sebri ◽  
Stefano Triberti ◽  
Gabriella Pravettoni
Keyword(s):  
Decision Making ◽  
Iowa Gambling Task ◽  
Attentional Focus ◽  
The Body ◽  
Future Research ◽  
Decision Making Process ◽  
Long Term Outcomes ◽  
Decision Making Processes ◽  
Multiple Conditions

AbstractWhen attention is focused on self representation(s), the ability to evaluate one’s internal sensations is enhanced, according to previous research by Ainley and colleagues (Consciousness and Cognition, 22(4), 1231–1238, 2013). Self-representations are usually distinguished between bodily and narrative. Both bodily and narrative representations improve decision-making processes, in that the consideration of alternatives is informed by sensations experienced deep inside the body (e.g., anxiety) as suggest by the literature (Noël, Brevers & Bechara in Frontiers in Psychiatry, 4, 179,  2013). The objective of the present study is to analyze the decision-making process in multiple conditions of stimulated self-representations. Participants played the Iowa Gambling Task three times (a baseline without stimuli and two randomly ordered stimulations to prime bodily and narrative self-representations). While no significant differences emerged regarding advantageous choices, participants showed loss frequency bias in the condition with bodily-self representation priming. Two interpretations are proposed: bodily-self focus acted as a distractor diminishing participants’ commitment to long term outcomes or enhanced interoception promoted aversion to losses. Directions are given for future research and clinical implications.

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