Deferoxamine Reduces Cavity Size in the Brain After Intracerebral Hemorrhage in Aged Rats

Fourth Ventricle ◽

Transtentorial Herniation ◽

Intracerebral Bleeding ◽

Rare Phenomenon ◽

ABSTRACT:Background:Transtentorial herniation of large cerebral fragments is a rare phenomenon.Method:Case StudyResults:Examination of the brain of a 35-year-old male showed massive intracerebral hemorrhage resulting in displacement of basal ganglia components into the fourth ventricle.Conclusions:Sufficiently rapid intracerebral bleeding can dissect fragments of cerebrum and displace them long distances across the tentorial opening.

MSC Secretome as a Promising Tool for Neuroprotection and Neuroregeneration in a Model of Intracerebral Hemorrhage

Pharmaceutics ◽

10.3390/pharmaceutics13122031 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2031

Author(s):

Maxim Karagyaur ◽

Stalik Dzhauari ◽

Nataliya Basalova ◽

Natalia Aleksandrushkina ◽

Georgy Sagaradze ◽

...

Keyword(s):

Neurological Outcome ◽

Multipotent Mesenchymal Stromal Cells ◽

Lesion Volume ◽

Therapeutic Approaches ◽

Beneficial Effects ◽

Tissue Repair And Regeneration ◽

Promising Tool ◽

Neurologic Disorders ◽

Multipotent mesenchymal stromal cells (MSCs) are considered to be critical contributors to injured tissue repair and regeneration, and MSC-based therapeutic approaches have been applied to many peripheral and central neurologic disorders. It has been demonstrated that the beneficial effects of MSC are mainly mediated by the components of their secretome. In the current study, we have explored the neuroprotective potential of the MSC secretome in a rat model of intracerebral hemorrhage and shown that a 10-fold concentrated secretome of human MSC and its combination with the brain-derived neurotrophic factor (BDNF) provided a better survival and neurological outcome of rats within 14 days of intracerebral hemorrhage compared to the negative (non-treated) and positive (BDNF) control groups. We found that it was due to the ability of MSC secretome to stimulate neuron survival under conditions of glutamate-induced neurotoxicity. However, the lesion volume did not shrink in these rats, and this also correlated with prominent microglia activation. We hypothesize that this could be caused by the species-specificity of the used MSC secretome and provide evidence to confirm this. Thus, we have found that allogenic rat MSC secretome was more effective than xenogenic human MSC secretome in the rat intracerebral hemorrhage model: it reduced the volume of the lesion and promoted excellent survival and neurological outcome of the treated rats.

Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu

10.1101/2020.11.10.375675 ◽

2020 ◽

Author(s):

Brittany A. Goods ◽

Michael H. Askenase ◽

Erica Markarian ◽

Hannah E. Beatty ◽

Riley Drake ◽

...

Keyword(s):

Single Cell ◽

Brain Tissue ◽

Cellular Response ◽

Tissue Injury ◽

Brain Inflammation ◽

Therapeutic Interventions ◽

Acute Injury ◽

The Brain ◽

Over Time

ABSTRACTIntracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury, particularly over time, in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Haemorrhage Evacuation (MISTIEIII) trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-sequencing, we characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution for the first time. Our analysis revealed rapid shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic re-bleed (second local exposure to blood) that our transcriptional data indicated occurred more than 30 hours prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods like scRNA-seq can inform our understanding of complex intracerebral events.

Nuclear Estradiol and Cytosol Progestin Receptor Concentrations in the Brain and the Pituitary Gland and Sexual Behavior in Ovariectomized Estradiol-Treated Middle-Aged Rats*

Endocrinology ◽

10.1210/endo-115-2-810 ◽

1984 ◽

Vol 115 (2) ◽

pp. 810-816 ◽

Cited By ~ 44

Author(s):

PHYLLIS M. WISE ◽

BRUCE PARSONS

Keyword(s):

Sexual Behavior ◽

Pituitary Gland ◽

Aged Rats ◽

Middle Aged ◽

Progestin Receptor ◽

Butin attenuates brain edema in a rat model of intracerebral hemorrhage by anti inflammatory pathway

Translational Neuroscience ◽

10.1515/tnsci-2018-0002 ◽

2018 ◽

Vol 9 (1) ◽

pp. 7-12 ◽

Cited By ~ 1

Author(s):

Peiyu Li ◽

Cheng Jiwu

Keyword(s):

Brain Edema ◽

Treated Group ◽

Control Group ◽

Lesion Volume ◽

Dependent Manner ◽

Neurological Score ◽

Factor Α ◽

The Brain ◽

Brain Tissues

Abstract Background This study evaluates the effect of butin against brain edema in intracerebral hemorrhage (ICH). Methodology ICH was induced by injecting bacterial collagenase in the brain and all the animals were separated into four groups such as control group, ICH group treated with vehicle, Butin 25 and 50 mg/kg group receives butin (25 and 50 mg/kg, i.p.)60 min after the induction of ICH in all animals. One day after neurological score, hemorrhagic injury and expressions of protein responsible for apoptosis and inflammatory cytokines were assessed in the brain tissue of ICH rats. Result Neurological scoring significantly increased and hemorrhagic lesion volume decreased in butin treated group of rats compared to ICH group. However, treatment with butin significantly decreases the ratio of Bax/Bcl-2 and protein expression of Cleaved caspase-3 than ICH group in dose dependent manner. Level of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) in the brain tissues were significantly decreased in the butin treated group than ICH group. In addition butin attenuates the altered signaling pathway of NF-κB in the brain tissues of ICH rats. Conclusion Our study concludes that butin attenuates the altered behavior and neuronal condition in ICH rats by reducing apoptosis and inflammatory response.

Abstract TMP82: Increased Intracerebral Hemorrhage During Acute and Chronic Hypertension in Alzheimer's Transgenic Mice

Stroke ◽

10.1161/str.44.suppl_1.atmp82 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

David H Cribbs ◽

Giselle Passos ◽

Vitaly Vasilevko

Keyword(s):

Risk Factor ◽

Transgenic Mice ◽

Amyloid Precursor Protein ◽

Significant Risk ◽

Significant Risk Factor ◽

Chronic Hypertension ◽

Cerebrovascular System ◽

The Brain ◽

Tg2576 Mice

Hypertension is a major risk factor for intracerebral hemorrhage (ICH), and the accumulation of amyloid-beta (Aβ) in the cerebrovascular system, cerebral amyloid angiopathy (CAA), is also a significant risk factor for intracerebral hemorrhage ICH. Currently, there are no animal studies demonstrating a direct involvement of hypertension in the accumulation of Alzheimer’s disease-like pathology. To address this issue we have developed several mouse models that combine hypertension protocols with amyloid precursor protein (APP) transgenic mice (Tg2576), which accumulate significant CAA in the large cerebral vessels and the meninges by 18 months of age. The goal of this study was to determine the effect of acute and chronic hypertension on ICH in wildtype and a transgenic mouse model overexpressing a mutant human amyloid precursor protein (Tg2576 mice) associated with early onset AD and CAA. Fifteen-month-old Tg2576 mice and non-transgenic (nTg) littermates were treated with an angiotensin II (AngII) infusion (1000 ng/kg/min) and L-NAME (100 mg/kg/day) in drinking water to produce chronic hypertension. One week later, transient acute hypertension was induced by daily AngII injections (0.5 μg/g, s.c., twice daily) to produce ICH. A similar increase in mean blood pressure was observed in Tg2576 and nTg mice when evaluated 2 weeks after initiation of treatment. However Tg2576 mice had a higher incidence of signs of stroke compared with nTg littermates (P > 0.05). These data suggest that the accumulation of Aβ in the brain has an important role in development of ICH. Moreover, there was robust glial activation and increase in CAA in the gray matter of Tg2576 mice showing that hypertension may affect gray as well as white matter in the brain. Further studies may provide insights into the hypertension-induced changes in the cerebral vascular system that initiated the increase in CAA. The accumulation of Aβ in the cerebrovascular system is a significant risk factor for intracerebral hemorrhage (ICH), and has been linked to endothelial transport failure and blockage of perivascular drainage. While management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA.

Abstract 178: Cholesterol Limits Macrophage Activation in Response to Intracerebral Hemorrhage-Relevant Signals

Stroke ◽

10.1161/str.51.suppl_1.178 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Jonathan H DeLong ◽

Sofia Velazquez ◽

Margaret J Landreneau ◽

Lauren H Sansing

Keyword(s):

Macrophage Activation ◽

Cholesterol Content ◽

Brain Parenchyma ◽

Activation Markers ◽

Multiple Systems ◽

Murine Bone Marrow ◽

Inflammatory Phenotype ◽

Injury Models ◽

Introduction: In response to intracerebral hemorrhage (ICH), monocytes are recruited to the brain parenchyma, where they differentiate into macrophages and contribute to a pathological inflammatory response. However, by day 3 after ICH, brain macrophages have adopted a more reparative phenotype and are important for clearance of apoptotic cells and recovery. The signals that control this inflammatory to reparative differentiation are incompletely understood, but cholesterol has been found to limit macrophage activation in multiple systems. The brain has the highest cholesterol content of any organ and we hypothesized that cholesterol uptake by macrophages limits inflammation and promotes the development of reparative macrophages following ICH. Methods and Results: Murine bone marrow-derived macrophages were stimulated with a cocktail of thrombin, S100A8, and IL-1b in order to mimic the Danger-Associated Molecular Patterns present in the brain after ICH (ICH-DAMP), LPS, or vehicle for 14-18 hours. Cytokine production was quantified by cytometric bead array and activation markers by flow cytometry. ICH-DAMP was found to upregulate CCL2, IL-6 and TNF, recapitulating the inflammatory phenotype seen in the first days after ICH. However, when cells were stimulated in the presence of cholesterol, production of CCL2, IL-6, and TNF were limited. Dectin-1 has inhibitory properties in some sterile injury models. ICH-DAMP was found to limit expression of dectin-1, and cholesterol reversed this inhibition. Exposure to exogenous cholesterol also upregulated the cholesterol transporter ABCA1, allowing cells to efflux excess cholesterol. The drug Valspodar was therefore used to block cholesterol efflux and was found to further limit ICH-DAMP-mediated upregulation of CCL2. Conclusion: These results suggest that the cholesterol in the brain may limit macrophage activation in response to the stimuli present during intracerebral hemorrhage.