scholarly journals Histone Deacetylase Inhibitor Scriptaid Alleviated Neurological Dysfunction after Experimental Intracerebral Hemorrhage in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Heng Yang ◽  
Wei Ni ◽  
Hanqiang Jiang ◽  
Yu Lei ◽  
Jiabin Su ◽  
...  
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Basal Ganglia ◽  
Intracerebral Hemorrhage ◽  
Autologous Blood ◽  
White Matter Injury ◽  
Neurological Dysfunction ◽  
Vehicle Group ◽  
Hematoma Volume ◽  
The Right

Objectives. To investigate the role of Scriptaid in reducing brain injury after intracerebral hemorrhage (ICH) in mice. Methods. An ICH model was constructed by injecting autologous blood into the right basal ganglia in mice. The animals were administered 3.5 mg/kg of Scriptaid intraperitoneally after ICH. The hematoma volume and hemoglobin level were measured to examine hematoma resolution. A behavior test and brain edema and white matter injury examinations indicated brain injury after ICH. Results. Scriptaid treatment promoted hematoma resolution and reduced the hematoma volume 7 d after ICH compared with the vehicle group (P<0.05). Scriptaid treatment also alleviated the brain water content in the ipsilateral basal ganglia (P<0.05) and cortex (P<0.01) 3 d after ICH. In addition, Scriptaid improved neurological function recovery and alleviated white matter injury 35 d after ICH. Conclusions. Scriptaid can protect against brain injury after ICH and may be considered a new medical therapy method for ICH.

Effectiveness of minocycline in acute white matter injury after intracerebral hemorrhage

2016 ◽  
Vol 126 (6) ◽  
pp. 1855-1862 ◽  
Author(s):  
Xiang Zou ◽  
Zehan Wu ◽  
Wei Zhu ◽  
Liang Chen ◽  
Ying Mao ◽  
...  
Keyword(s):  
White Matter ◽  
Intracerebral Hemorrhage ◽  
Autologous Blood ◽  
Critical Role ◽  
White Matter Injury ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Injection Group ◽  
Jnk Activation

OBJECTIVEIntracerebral hemorrhage (ICH) is a fatal disease with high morbidity and mortality, which may be followed by white matter injury (WMI) due to the local oxidizing reaction induced by iron (Fe). In this study, the authors examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI and c-Jun N-terminal kinase (JNK) activation in rats.METHODSThirty-six male Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe + minocycline. Another 36 rats had an intracaudate injection of autologous blood and were treated with minocycline or vehicle (saline). Biomarkers of both WMI and JNK activation were examined.RESULTSIn the Fe-injection group, minocycline suppressed WMI labeled by β-amyloid precursor protein (β-APP) and degraded myelin basic protein (dMBP)/MBP ratio. Protein levels of phosphorylated-JNK were increased after Fe injection, and could be suppressed by minocycline treatment. In the autologous blood–injection group, β-APP and dMBP/MBP levels increased in the ipsilateral site compared with the contralateral site, which could be suppressed by 7 days of minocycline intervention.CONCLUSIONSIron plays a critical role in WMI after ICH, which can be suppressed by minocycline through reducing the damage induced by Fe.

scholarly journals Role of Lipocalin-2 in Brain Injury after Intracerebral Hemorrhage

2015 ◽  
Vol 35 (9) ◽  
pp. 1454-1461 ◽  
Author(s):  
Wei Ni ◽  
Mingzhe Zheng ◽  
Guohua Xi ◽  
Richard F Keep ◽  
Ya Hua
Keyword(s):  
Brain Injury ◽  
Basal Ganglia ◽  
Intracerebral Hemorrhage ◽  
Autologous Blood ◽  
Sham Operation ◽  
Intracerebral Injection ◽  
Lipocalin 2 ◽  
Brain Swelling ◽  
Male Adult

Lipocalin-2 (LCN2) is a siderophore-binding protein involved in cellular iron transport and neuroinflammation. Both iron and inflammation are involved in brain injury after intracerebral hemorrhage (ICH) and this study examined the role of LCN2 in such injury. Male adult C57BL/6 wild-type (WT) or LCN2-deficient (LCN2-/-) mice had an intracerebral injection of autologous blood or FeCl2. Control animals had a sham operation or saline injection. T2-weighted magnetic resonance imaging and behavioral tests were performed at days 1, 3, 7, 14, and 28 after injection. In WT mice, brain LCN2 levels were increased in the ipsilateral basal ganglia after ICH or iron injection. Lipocalin-2-positive cells were astrocytes, microglia, neurons, and endothelial cells. Intracerebral hemorrhage resulted in a significant increase in ferritin expression in the ipsilateral basal ganglia. Compared with WT mice, ICH caused less ferritin upregulation, microglia activation, brain swelling, brain atrophy, and neurologic deficits in LCN2-/- mice ( P < 0.05). The size of the lesion induced by FeCl2 injection as well as the degree of brain swelling and blood–brain barrier disruption were also less in LCN2-/- mice ( P < 0.05). These results suggest a role of LCN2 in enhancing brain injury and iron toxicity after ICH.

scholarly journals White Matter Injury in Early Brain Injury after Subarachnoid Hemorrhage

2018 ◽  
Vol 28 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Jinwei Pang ◽  
Jianhua Peng ◽  
Ping Yang ◽  
Li Kuai ◽  
Ligang Chen ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
White Matter ◽  
Early Brain Injury ◽  
Therapeutic Strategies ◽  
White Matter Injury ◽  
High Morbidity ◽  
Normal Brain ◽  
Neurological Outcomes ◽  
Multiple Substrates

Subarachnoid hemorrhage (SAH) is a major cause of high morbidity, disability, and mortality in the field of neurovascular disease. Most previous SAH studies have focused on improving cerebral blood flow, reducing cerebral vasospasm, reducing neuronal calcium overload, and other treatments. While these studies showed exciting findings in basic science, therapeutic strategies based on the findings have not significantly improved neurological outcomes in patients with SAH. Currently, the only drug proven to effectively reduce the neurological defects of SAH patients is nimodipine. Current advances in imaging technologies in the field of stroke have confirmed that white matter injury (WMI) plays an important role in the prognosis of types of stroke, and suggests that WMI protection is essential for functional recovery and poststroke rehabilitation. However, WMI injury in relation to SAH has remained obscure until recently. An increasing number of studies suggest that the current limitations for SAH treatment are probably linked to overlooked WMI in previous studies that focused only on neurons and gray matter. In this review, we discuss the biology and functions of white matter in the normal brain, and discuss the potential pathophysiology and mechanisms of early brain injury after SAH. Our review demonstrates that WMI encompasses multiple substrates, and, therefore, more than one pharmacological approach is necessary to preserve WMI and prevent neurobehavioral impairment after SAH. Strategies targeting both neuronal injury and WMI may potentially provide a novel future for SAH knowledge and treatment.

Loss of Consciousness Is Related to White Matter Injury in Mild Traumatic Brain Injury

2016 ◽  
Vol 33 (22) ◽  
pp. 2000-2010 ◽  
Author(s):  
Elisabeth A. Wilde ◽  
Xiaoqi Li ◽  
Jill V. Hunter ◽  
Ponnada A. Narayana ◽  
Khader Hasan ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
White Matter Injury ◽  
Loss Of Consciousness

Abstract TP351: Axl/Mer Receptor Tyrosine Kinase Mediates Erythrophagocytosis-Induced Macrophage Reparative Phenotype and Brain Recovery in Experimental Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Che-Feng Chang ◽  
Brittany A Thomas ◽  
Michael Askenase ◽  
Arthur F Steinschneider ◽  
Youxi Ai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Autologous Blood ◽  
Phenotypic Change ◽  
Macrophage Phenotype ◽  
Double Knockout ◽  
Brain Recovery

Introduction: Local inflammation contributes to both brain injury and recovery after intracerebral hemorrhage (ICH). Our previous studies have shown brain-infiltrating macrophages (BIMs) aggravate early brain injury after ICH; however, BIMs increase scavenger receptor CD36 levels over time, and hematoma clearance is delayed in the absence of BIMs. The mechanism that mediates BIMs phenotypic change in the ICH brain is elusive. In this study, we delineate the dynamic transcriptome profile of BIMs after ICH and test potential mediator that might modulate BIMs polarity in ICH. Methods: Autologous blood injection ICH model and thrombin-treated bone marrow-derived macrophages (BMDM) were used to mimic ICH in vivo and in vitro . BIMs were isolated by FACS, and the 780 transcriptome of BIMs were determined using NanoString. Flow cytometry and RT-qPCR were performed to detect the frequency of phosphatidylserine-positive (eryptotic) RBCs and to assess BIMs phenotype in the perihematomal tissue. Erythrophagocytosis of eryptotic RBCs was identified by immunofluorescence and microscopy. Neurologic deficit was evaluated by cylinder test. Axl/Mer receptor tyrosine kinase double knockout (AM DKO) mice, AM DKO bone-marrow chimeras, and AM DKO BMDM were used to evaluate the function of Axl/Mer on macrophage phenotype and on brain recovery after ICH. Results: BIMs highly expressed proinflammatory transcripts such as cd86 , tlr2 , nlrp3 , and tnf at days 1 and 3 post-ICH; these were decreased at days 7 and 10. Transcripts relevant to efferocytosis ( axl ) and lysosome formation ( cd63 ) increased from days 3 to 10 post-ICH. At days 1 and 3, phosphatidylserine levels was increased on RBCs in the ICH brain. Engulfment of eryptotic RBCs reduced proinflammatory phenotype of BMDM. Thrombin-stimulated AM DKO BMDM had reduced erythrophagocytosis ability and increased tnf and il-6 gene expression. AM DKO mice and AM DKO chimeras had low CD36 and high MHC II levels on BIMs and had worse functional outcome after ICH. Conclusions: BIMs initially express proinflammatory phenotype and then switch to a reparative phenotype after ICH. Axl/Mer is involved in regulation of macrophage polarity through modulating erythrophagocytosis ability and contributes to ICH brain recovery.

Distributed grey and white matter deficits in hyperkinetic disorder: MRI evidence for anatomical abnormality in an attentional network

2001 ◽  
Vol 31 (8) ◽  
pp. 1425-1435 ◽  
Author(s):  
S. OVERMEYER ◽  
E. T. BULLMORE ◽  
J. SUCKLING ◽  
A. SIMMONS ◽  
S. C. R. WILLIAMS ◽  
...  
Keyword(s):  
White Matter ◽  
Basal Ganglia ◽  
Large Scale ◽  
Grey Matter ◽  
Right Hemisphere ◽  
Hyperkinetic Disorder ◽  
Normal Children ◽  
Pyramidal Tracts ◽  
Icd 10 ◽  
The Right

Background. Previous neuroimaging studies of children with attention deficit hyperactivity disorder (ADHD) have demonstrated anatomic and functional abnormalities predominantly in frontal and striatal grey matter. Here we report the use of novel image analysis methods, which do not require prior selection of regions of interest, to characterize distributed morphological deficits of both grey and white matter associated with ADHD.Methods. Eighteen children with a refined phenotype of ADHD, who also met ICD-10 criteria for hyperkinetic disorder (mean age 10·4 years), and 16 normal children (mean age 10·3 years) were compared using magnetic resonance imaging. The groups were matched for handedness, sex, height, weight and head circumference. Morphological differences between groups were estimated by fitting a linear model at each voxel in standard space, applying a threshold to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels, and testing cluster ‘mass’, or the sum of suprathreshold voxel statistics in each 2D cluster, by repeated random resampling of the data.Results. The hyperkinetic children had significant grey matter deficits in right superior frontal gyrus (Brodmann area (BA) 8/9), right posterior cingulate gyrus (BA 30) and the basal ganglia bilaterally (especially right globus pallidus and putamen). They also demonstrated significant central white matter deficits in the left hemisphere anterior to the pyramidal tracts and superior to the basal ganglia.Conclusions. This pattern of spatially distributed grey matter deficit in the right hemisphere is compatible with the hypothesis that ADHD is associated with disruption of a large scale neurocognitive network for attention. The left hemispheric white matter deficits may be due to dysmyelination.

scholarly journals A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury

2017 ◽  
Vol 38 (10) ◽  
pp. 1818-1827 ◽  
Author(s):  
Raghavendar Chandran ◽  
TaeHee Kim ◽  
Suresh L Mehta ◽  
Eshwar Udho ◽  
Vishal Chanana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Function ◽  
Neurological Dysfunction ◽  
Vehicle Group ◽  
Lesion Volume ◽  
Post Injury ◽  
Cortical Contusion ◽  
Nrf2 Activator

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice. Genetic deletion of NOX2 improved, while Nrf2 worsened the post-TBI motor function recovery and lesion volume indicating that decreasing ROS levels might be beneficial after TBI. Treatment with either apocynin (NOX2 inhibitor) or TBHQ (Nrf2 activator) alone significantly improved the motor function after TBI, but had no effect on the lesion volume, compared to vehicle control. Whereas, the combo therapy (apocynin + TBHQ) given at either 5 min/24 h or 2 h/24 h improved motor and cognitive function and decreased cortical contusion volume compared to vehicle group. Thus, both the generation and disposal of ROS are important modulators of oxidative stress, and a combo therapy that prevents ROS formation and potentiates ROS disposal concurrently is efficacious after TBI.

Sign in / Sign up

Export Citation Format

Share Document