scholarly journals Acute and chronic stage adaptations of vascular architecture and cerebral blood flow in a mouse model of TBI

2018 ◽  
Author(s):  
Joe Steinman ◽  
Lindsay S. Cahill ◽  
Margaret M. Koletar ◽  
Bojana Stefanovic ◽  
John G. Sled
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Vessel Density ◽  
Vascular Architecture ◽  
Two Photon ◽  
Brain Vasculature ◽  
The Impact ◽  
The Brain ◽  
Time Point

AbstractThe 3D organization of cerebral blood vessels determines the overall capacity of the cerebral circulation to meet the metabolic requirements of the brain. This study used Arterial Spin Labeling (ASL) MRI with a hypercapnic challenge and ex vivo Serial Two-Photon Tomography (STPT) to examine the relationship between blood flow and 3D microvascular structure following traumatic brain injury (TBI) in a mouse. Mice were exposed to a controlled cortical impact TBI and allowed to recover for either 1 day or 4 weeks. At each time point, ASL MRI was performed to quantify cerebral perfusion and the brain vasculature was imaged in 3D with STPT. Registration of ASL to STPT enabled flow changes to be related to the underlying microvascular structure in each ASL voxel. Hypoperfusion under rest and hypercapnia was observed both 1 day and 4 weeks post-TBI. Vessel density and vascular volume were reduced 1 day post-TBI, recovering by 4 weeks; however, the reorganized vasculature at the latter time point possessed an abnormal radial pattern. Our findings demonstrate functionally significant long-term changes in the vascular architecture following injury and illustrate why metrics beyond traditional measures of vessel density are required to understand the impact of vascular structure on function.

Ultrasound Measurements of Intracranial Structures in Growth-Restricted Neonates with Fetal Blood Flow Redistribution: A Pilot Observational Study

Neonatology ◽  
2020 ◽  
Vol 117 (4) ◽  
pp. 446-452
Author(s):  
Pramod Pharande ◽  
Mohan Krishnamurthy ◽  
Gillian Whiteley ◽  
Arun Sasi ◽  
Atul Malhotra
Keyword(s):  
Blood Flow ◽  
Observational Study ◽  
Prospective Observational Study ◽  
Brain Structures ◽  
Cranial Ultrasound ◽  
Fetal Blood ◽  
The Impact ◽  
The Brain ◽  
Blood Flow Redistribution

<b><i>Background:</i></b> Fetal growth restriction (FGR) is associated with neonatal and long-term neuro-morbidity. Preferential redistribution of blood flow to the brain is a common antenatal adaptation in FGR. The impact of this “brain sparing,” which may signify severity of FGR, on the growth of brain structures has not been studied. <b><i>Aim:</i></b> To compare corpus callosum (CC), cerebellar, and ventricular measurements of FGR neonates with evidence of fetal blood flow redistribution with those of gestation-matched appropriately grown (AGA) neonates. <b><i>Methods:</i></b> This was a pilot, prospective observational study conducted at a tertiary level neonatal unit in Melbourne, Australia. Cranial ultrasound was done between days 1 and 3 of life in FGR and AGA neonates. <b><i>Results:</i></b> Cranial ultrasound on 20 FGR, gestation (mean ± SD) 31.4 ± 3.1 weeks, weight 1,205 ± 463 g, and 20 AGA neonates, 31.1 ± 3.0 weeks, 1,668 ± 490 g, was performed. CC length was significantly decreased in FGR neonates as compared to AGA neonates (35.28 ± 3.47 vs. 38.83 ± 4.05 mm, <i>p</i> = 0.0002). CC was significantly thinner at genu (3.36 ± 0.66 vs. 4.04 ± 0.83 mm, <i>p</i> = 0.007), body (1.97 ± 0.36 vs. 2.27 ± 0.39 mm, <i>p</i> = 0.02), and splenium (4.07 ± 0.76 vs. 4.72 ± 0.75 mm, <i>p</i> = 0.003) in FGR vs. AGA neonates. CC-fastigium length was also significantly decreased (39.65 ± 3.87 vs. 41.96 ± 4.50 mm, <i>p</i> = 0.04). Similarly, FGR neonates showed decreased transverse cerebellar diameter (36.15 ± 5.51 vs. 38.81 ± 7.21 mm, <i>p</i> = 0.02), but ventricular measurements were comparable. In multivariate analysis, these differences were evident independent of the birth weight. <b><i>Conclusions:</i></b>CC and cerebellar measurements are significantly smaller in FGR neonates with fetal blood flow redistribution, which warrants further study.

scholarly journals Toxoplasma gondii injected neurons localize to the cortex and striatum and have altered firing

2021 ◽  
Author(s):  
Oscar A. Mendez ◽  
Emiliano Flores Machado ◽  
Jing Lu ◽  
Anita A. Koshy
Keyword(s):  
Toxoplasma Gondii ◽  
Single Neuron ◽  
Latent Infection ◽  
Ex Vivo ◽  
Medium Spiny Neurons ◽  
Patch Clamping ◽  
Spiny Neurons ◽  
The Brain ◽  
Mapping Program

AbstractToxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma-injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. Using immunofluorescence co-localization assays, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2+) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2+). As MSNs have highly characterized electrophysiology, we used ex vivo slices from infected mice to perform single neuron patch-clamping on striatal TINs and neighboring uninfected MSNs (bystander MSNs). These studies demonstrated that TINs have highly abnormal electrophysiology, while the electrophysiology of bystander MSNs was akin to that of MSNs from uninfected mice. Collectively, these data offer new neuroanatomic and electrophysiologic insights into CNS toxoplasmosis.

scholarly journals The Causes and Long-Term Consequences of Viral Encephalitis

2021 ◽  
Vol 15 ◽  
Author(s):  
Karen Bohmwald ◽  
Catalina A. Andrade ◽  
Nicolás M. S. Gálvez ◽  
Valentina P. Mora ◽  
José T. Muñoz ◽  
...  
Keyword(s):  
Viral Encephalitis ◽  
Viral Infections ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Brain Inflammation ◽  
High Morbidity ◽  
Stiff Neck ◽  
The Impact ◽  
The Brain

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

scholarly journals Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

2019 ◽  
Author(s):  
Felix C. Nebeling ◽  
Stefanie Poll ◽  
Lena C. Schmid ◽  
Manuel Mittag ◽  
Julia Steffen ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dendritic Spines ◽  
Synapse Formation ◽  
Brain Parenchyma ◽  
Two Photon ◽  
Contact Rates ◽  
Health And Disease ◽  
The Impact ◽  
The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

Keep Your Brain Tissue Healthy

2021 ◽  
pp. 27-66
Author(s):  
Charles Alessi ◽  
Larry W. Chambers ◽  
Muir Gray
Keyword(s):  
Physical Activity ◽  
Immune System ◽  
Inflammatory Response ◽  
Stress Reduction ◽  
Indirect Effects ◽  
Cognitive Abilities ◽  
Direct And Indirect Effects ◽  
The Impact ◽  
The Brain

This chapter starts by advising how to reduce the impact of stress. When stress becomes long term, the immune system becomes less sensitive to cortisol, and since inflammation is partly regulated by this hormone, this decreased sensitivity heightens the inflammatory response and allows inflammation to get out of control, increasing our risk of many diseases. You can reduce your stress yourself through a variety of methods, including physical activity and mindfulness-based stress reduction. Adequate sleep is also a major factor that can improve cognitive abilities and reduce the risk of dementia, and this chapter outlines what we need to know about sleep cycles, insomnia, and sleep disordered breathing, and how to sleep more and sleep better. The chapter then covers how to protect your brain from over medication (polypharmacy). It finishes by discussing how to maintain and indeed increase your levels of physical activity, and how increasing physical activity has both direct and indirect effects on the brain.

Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 1064-1069 ◽  
Author(s):  
Alin Borha ◽  
Audrey Chagnot ◽  
Romain Goulay ◽  
Evelyne Emery ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Decompressive Craniectomy ◽  
Early Time ◽  
Brain Parenchyma ◽  
Late Time ◽  
Perivascular Spaces ◽  
Early Time Point ◽  
The Impact ◽  
The Brain ◽  
Brain Homeostasis ◽  
Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

scholarly journals Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19

2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  
Keyword(s):  
Organ Damage ◽  
Multiple Organ ◽  
Global Pandemic ◽  
Organ Systems ◽  
Future Challenges ◽  
The Central Nervous System ◽  
The Impact ◽  
Collaborative Efforts ◽  
The Brain

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

scholarly journals The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 435 ◽  
Author(s):  
Anna Winiarska-Mieczan ◽  
Ewa Baranowska-Wójcik ◽  
Małgorzata Kwiecień ◽  
Eugeniusz R. Grela ◽  
Dominik Szwajgier ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Negative Impact ◽  
Functional Disorders ◽  
Brain Functions ◽  
Diet Supplements ◽  
The Impact ◽  
The Brain ◽  
All Diseases

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.

scholarly journals Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

2016 ◽  
Vol 37 (3) ◽  
pp. 994-1005 ◽  
Author(s):  
Lindsay S Cahill ◽  
Lisa M Gazdzinski ◽  
Albert KY Tsui ◽  
Yu-Qing Zhou ◽  
Sharon Portnoy ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Tissue ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Cell Model ◽  
Ex Vivo ◽  
Tissue Hypoxia ◽  
Brain Physiology ◽  
The Brain

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

scholarly journals Two-Photon Microscopy as a Tool to Study Blood Flow and Neurovascular Coupling in the Rodent Brain

2012 ◽  
Vol 32 (7) ◽  
pp. 1277-1309 ◽  
Author(s):  
Andy Y Shih ◽  
Jonathan D Driscoll ◽  
Patrick J Drew ◽  
Nozomi Nishimura ◽  
Chris B Schaffer ◽  
...  
Keyword(s):  
Blood Flow ◽  
Laser Scanning ◽  
Vascular System ◽  
Neurovascular Coupling ◽  
Laser Scanning Microscopy ◽  
Small Scale ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Rats And Mice ◽  
The Brain

The cerebral vascular system services the constant demand for energy during neuronal activity in the brain. Attempts to delineate the logic of neurovascular coupling have been greatly aided by the advent of two-photon laser scanning microscopy to image both blood flow and the activity of individual cells below the surface of the brain. Here we provide a technical guide to imaging cerebral blood flow in rodents. We describe in detail the surgical procedures required to generate cranial windows for optical access to the cortex of both rats and mice and the use of two-photon microscopy to accurately measure blood flow in individual cortical vessels concurrent with local cellular activity. We further provide examples on how these techniques can be applied to the study of local blood flow regulation and vascular pathologies such as small-scale stroke.

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