Neurovascular

Retinal vascular diseases such as diabetic retinopathy and retinopathy of prematurity are major causes of visual loss. Although the focus of a great deal of research has been on the aetiology of vascular growth, it is now emerging that anomalies in other retinal cell types, especially glial cells, occur very early in the course of the disease. Glial cells have major roles in every stage of disease, from the earliest subtle variations in neural function, to the development of epi-retinal membranes and tractional detachment. Therefore, having a firm understanding of the function of retinal glia is important in our understanding of retinal disease and is crucial for the development of new treatment strategies.

The already established and widely used intravenous application of recombinant tissue plasminogen activator as a reopening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient's outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms. This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode-and-regeneration to late stage translational or early stage clinical investigations.

Stroke is the commonest neurological cause of morbidity and mortality all over the world being the third leading cause of death. Estimation of stroke risks in population is not only helpful for healthcare providers but also important to identify persons at elevated risk and to select proper treatments in clinical trials. The aim of the present study was to identify the prevalence of common modifiable risk factors for ischemic stroke in Pakistan. Patients of either sex above the age of 25 yrs who were admitted to Neurology Ward or came to OPD in Jinnah Post Graduate Medical Centre were included in the study. Type of stroke was identified by brain CT scans or MRI and risk factors for stroke and other details were noted on a proforma. Out of 55 patients studied for present study, 78% were males and 22% were females. Most of them belonged to low socioeconomic status and almost 50% were having family history of stroke. Most of the patients had multiple risk factors which included: hypertension (65%), smoking (32%), diabetes mellitus (36.3%), dyslipidemia (32.7%), coronary artery disease (9%), obesity (18%), epilepsy (16.3%) and left ventricular hypertrophy (3.6%). On the basis of these findings, it can be concluded that hypertension, smoking, dyslipidemia and diabetes mellitus are major risk factors for stroke and might be considered as main targets for primary and secondary prevention of stroke.

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT1A, 5-HT2A, and 5-HT4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for th...

Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P < 0.001) and smaller baseline diffusion lesion volu...

Lymphocytes with "tailed" nuclei (LTN) which are easily observed in routine smears of peripheral blood are a biological response to radiation. In this article, we describe LTN as a biomarker that has the same origin as dicentric chromosome. In emergency situations, we recommend to use this simple biomarker in conjunction with hematological tests of the blood smears of the exposed persons.

BACKGROUND AND PURPOSE: For embolized cerebral aneurysms, the initial occlusion rate is the most powerful parameter to predict aneurysm rerupture and recanalization. However, the occlusion rate is only estimated subjectively in clinical routine. To minimize subjective bias, computer occlusion-rating (COR) was successfully validated for 2D images. To minimize the remaining inaccuracy of 2D-COR, COR was applied to 1.5T 3D MR imaging.

MATERIALS AND METHODS: Twelve experimental rabbit aneurysms were subjected to stent-assisted coil embolization followed by 2D DSA and 3D MR imaging. Subjective occlusion-rate (SOR) was estimated. Linear parameters (aneurysm length, neck width, parent vessel diameter) were measured
on 2D DSA and 3D MR imaging. The occlusion rate was measured by contrast medium-based identification of the nonoccluded 2D area/3D volume in relation to the total aneurysm 2D area/3D volume. 2D and 3D parameters were statistically compared.

RESULTS: There were no limiting metallic artifacts by using 3D MR imaging. Linear parameters (millimeters) were nearly identical on 2D DSA and 3D MR imaging (aneurysm length: 7.5 +- 2.6 versus 7.4 +- 2.5, P = .2334; neck width: 3.8 +- 1.0 versus 3.7 +- 1.1, P = .6377; parent vessel diameter: 2.7 +- 0.6 versus 2.7 +- 0.5, P = .8438), proving the high accuracy of 3D MR imaging. COR measured on 3D MR imaging was considerably lower (61.8% ⫾ 26.6%) compared with the following: 1) 2D-COR
(65.6% +- 27.1%, P = .0537) and 2) 2D-SOR estimations (69.2% +- 27.4%, P = .002). These findings demonstrate unacceptable bias in the current clinical standard SOR estimations.

CONCLUSIONS: 3D-COR of embolized aneurysms is easily feasible. Its accuracy is superior to that of the clinical standard 2D-SOR. The difference between 3D-COR and 2D-COR approached statistical significance. 3D-COR may add objectivity to the ability to stratify the risk of rerupture in embolized cerebral aneurysms.

Introduction: Chondromyxoid fibroma, CMF, is the least common benign cartilaginous tumor composed of chondroid and myxoid matrix. It is usually located eccentrically in distal femur or proximal tibia metaphysis. Juxtacortical Chondromyxoid fibroma which may be seen in unusual places such as intracortical, or sub periosteallocations is very unusual. Case report: A 16-year-old boy presented to us with a mildly painful distal tibial mass for one year. Imaging studies showed a protruded mixed radio-opaque, radio lucent lesion at posterior surface of distal tibial metaphysis, without soft tissue involvement. A biopsy was performed which showed Chondromyxoid fibroma. Curettage and bone grafting was done as the therapeutic modality. Conclusion: Chondromyxoid fibroma is usually not considered in the differential diagnosis of a painful, superficial lesion on a long bone. Other tumors such as periosteal chondroma, parosteal or periosteal osteosarcoma, parostealmyxoma, sub periosteal ganglion cyst, or periosteal osteoid osteoma are usually considered. Our case along with similar cases has proved that Juxtacortical CMF should be included in the differential diagnosis of a surface bony lesion.

Intracortical neural probes enable researchers to measure electrical and chemical signals in the brain. However, penetration injury from probe insertion into living brain tissue leads to an inflammatory tissue response. In turn, microglia are activated, which leads to encapsulation of the probe and release of pro-inflammatory cytokines. This inflammatory tissue response alters the electrical and chemical microen-vironment surrounding the implanted probe, which may in turn interfere with signal acquisition. Dexamethasone (Dex), a potent anti-inflammatory steroid, can be used to prevent and diminish tissue disruptions caused by probe implantation. Herein, we report retrodialysis administration of dexa-methasone while using in vivo two-photon microscopy to observe real-time microglial reaction to the implanted probe. Microdialysis probes under artificial cerebrospinal fluid (aCSF) perfusion with or without Dex were implanted into the cortex of transgenic mice that express GFP in microglia under the CX3CR1 promoter and imaged for 6 h. Acute morphological changes in microglia were evident around the microdialysis probe. The radius of microglia activation was 177.1 mm with aCSF control compared to 93.0 mm with Dex perfusion. T-stage morphology and microglia directionality indices were also used to quantify the microglial response to implanted probes as a function of distance. Dexamethasone had a profound effect on the microglia morphology and reduced the acute activation of these cells.

White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. We explored the relationship between baseline DTI characteristics of the thalamus, caudate, and putamen, and the volume and subsequent accrual of WMHs over a 4-year period in 56 community-dwelling older (≤75 years) individuals. Baseline thalamic fractional anisotropy (FA) was an independent predictor of WMH accrual. WMH accrual also correlated with baseline lacune count and baseline WMH volume, the latter showing the strongest predictive power, explaining 27.3% of the variance. The addition of...

Journal of Cerebral Blood Flow & Metabolism stands at the interface between basic and clinical neurovascular research, and features research on experimental, theoretical, and clinical aspects of brain circulation, metabolism and imaging. The journal is relevant to any physician ...

Specific neurochemicals measured with proton magnetic resonance spectroscopy (1H-MRS) may serve as biomarkers of pathological mechanism in the brain. We used high field in vivo1H-MRS to measure a detailed neurochemical profile after experimental traumatic brain injury (TBI) in rats. We characterized neurochemical changes in the contused cortex and the normal-appearing perilesional hippocampus over a time course from 1 hour to 2 weeks after injury. We found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. These changes provide evidence of altered cellular metabolic status after TBI, with specific compounds proposed to reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption. Our results support the utility of 1H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this app...

The adult central nervous system parenchyma is resistant to inflammation, but in juvenile rats the injection of inflammatory mediators, interleukin-1β for example, gives rise to extensive neutrophil recruitment and neutrophil-dependent blood–brain barrier breakdown. The factors that confer this resistant phenotype are unknown. In this study, the authors demonstrate that E- and P-selectin expression is increased to a similar extent in adult and juvenile brain after the intracerebral injection of IL-1β. Thus, the refractory nature of the brain parenchyma cannot be attributed to an absence of selectin expression. However, in injuries where the resistant characteristic of the brain parenchyma is compromised, and neutrophil recruitment occurs, selectin blockade may be an advantage. The authors investigated the contribution that selectins make to neutrophil recruitment during acute inflammation in the brain. The authors examined neutrophil recruitment by immunohistochemistry on brain sect...