scholarly journals Quantitative Assessment of Ischemic Pathology in Axons, Oligodendrocytes, and Neurons: Attenuation of Damage after Transient Ischemia

2000 ◽  
Vol 20 (5) ◽  
pp. 765-771 ◽  
Author(s):  
Valerio Valeriani ◽  
Deborah Dewar ◽  
James McCulloch
Keyword(s):  
White Matter ◽  
Quantitative Methods ◽  
Artery Occlusion ◽  
Axonal Damage ◽  
Therapeutic Interventions ◽  
Ischemic Damage ◽  
In Vivo Evaluation ◽  
White Matter Pathology ◽  
Cerebral Artery Occlusion

Axons and oligodendrocytes are vulnerable to cerebral ischemia. The absence of quantitative methods for assessment of white matter pathology in ischemia has precluded in vivo evaluation of therapeutic interventions directed at axons and oligodendrocytes. The authors demonstrate here that the quantitative extent of white matter pathology was reduced by restoration of cerebral blood flow after 2 hours of middle cerebral artery occlusion. Focal ischemia was induced in anesthetized rats by intraluminal thread placement, either transiently (for 2 hours) or permanently. At 24 hours after induction of ischemia, axonal damage was determined by amyloid precursor protein (APP) immunohistochemistry, and the ischemic insult to oligodendrocytes was assessed by Tau-1 immunostaining in the same sections. In adjacent sections, ischemic damage to neuronal perikarya was defined histologically. The hemispheric extent of axonal damage was reduced by 70% in the transiently occluded animals from that in permanently occluded animals. The volumes of oligodendrocyte pathology and of neuronal perikaryal damage were reduced by 62% and 58%, respectively, in the transiently occluded animals. These results demonstrate that this methodologic approach for assessing ischemic damage in axons and oligodendrocytes can detect relative alterations in gray and white matter pathology with intervention strategies.

In vivo evaluation of white matter pathology in patients of progressive supranuclear palsy using TBSS

2011 ◽  
Vol 54 (7) ◽  
pp. 771-780 ◽  
Author(s):  
Jitender Saini ◽  
Bhavani Shankara Bagepally ◽  
Mangalore Sandhya ◽  
Shaik Afsar Pasha ◽  
Ravi Yadav ◽  
...  
Keyword(s):  
White Matter ◽  
Progressive Supranuclear Palsy ◽  
In Vivo Evaluation ◽  
White Matter Pathology

scholarly journals Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain.

1991 ◽  
Vol 174 (2) ◽  
pp. 305-310 ◽  
Author(s):  
J K Relton ◽  
P J Strijbos ◽  
C T O'Shaughnessy ◽  
F Carey ◽  
R A Forder ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Brain ◽  
Therapeutic Potential ◽  
Artery Occlusion ◽  
Ischemic Damage ◽  
Endogenous Inhibitor ◽  
Annexin 1 ◽  
Marked Inhibition ◽  
Cerebral Artery Occlusion

Lipocortin-1 (annexin-1) is an endogenous peptide with antiinflammatory properties. We have previously demonstrated lipocortin immunoreactivity in certain glial cells and neurons in the rat brain (Strijbos, P.J.L.M., F.J.H. Tilders, F. Carey, R. Forder, and N.J. Rothwell. 1990. Brain Res. In press.), and have shown that an NH2-terminal fragment (1-188) of lipocortin-1 inhibits the central and peripheral actions of cytokines on fever and thermogenesis in the rat in vivo (Carey, F., R. Forder, M.D. Edge, A.R. Greene, M.A. Horan, P.J.L.M. Strijbos, and N.J. Rothwell. 1990. Am. J. Physiol. 259:R266; and Strijbos, P.J.L.M., J.L. Browning, M. Ward, R. Forder, F. Carey, M.A. Horan, and N.J. Rothwell. 1991. Br. J. Pharmacol. In press.). We now report that intracerebroventricular administration of lipocortin-1 fragment causes marked inhibition of infarct size (60%) and cerebral edema (46%) measured 2 h after cerebral ischemia (middle cerebral artery occlusion) in the rat in vivo. The lipocortin-1 fragment was effective when administered 10 min after induction of ischemia. Ischemia caused increased expression of lipocortin-1 around the area of infarction as demonstrated by immunocytochemistry. Intracerebroventricular injection of neutralizing antilipocortin-1 fragment antiserum increased the size of infarct (53%) and the development of edema (29%). These findings indicate that lipocortin-1 is an endogenous inhibitor of cerebral ischemia with considerable therapeutic potential.

scholarly journals Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma

2021 ◽  
Author(s):  
Thomaz R. Mostardeiro ◽  
Ananya Panda ◽  
Robert J. Witte ◽  
Norbert G. Campeau ◽  
Kiaran P. McGee ◽  
...  
Keyword(s):  
White Matter ◽  
Statistical Significance ◽  
Relaxation Times ◽  
Brain Structures ◽  
Centrum Semiovale ◽  
In Vivo Evaluation ◽  
Whole Brain ◽  
Mean Values ◽  
Caudate Head

Abstract Purpose MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate the clinical application of this technique in patients with meningioma. Materials and methods A whole-brain 3D isotropic 1mm3 acquisition under a 3.0T field strength was used to obtain MRF T1 and T2-based relaxometry values in 4:38 s. The accuracy of values was quantified by scanning a quantitative MR relaxometry phantom. In vivo evaluation was performed by applying the sequence to 20 subjects with 25 meningiomas. Regions of interest included the meningioma, caudate head, centrum semiovale, contralateral white matter and thalamus. For both phantom and subjects, mean values of both T1 and T2 estimates were obtained. Statistical significance of differences in mean values between the meningioma and other brain structures was tested using a Friedman’s ANOVA test. Results MR fingerprinting phantom data demonstrated a linear relationship between measured and reference relaxometry estimates for both T1 (r2 = 0.99) and T2 (r2 = 0.97). MRF T1 relaxation times were longer in meningioma (mean ± SD 1429 ± 202 ms) compared to thalamus (mean ± SD 1054 ± 58 ms; p = 0.004), centrum semiovale (mean ± SD 825 ± 42 ms; p < 0.001) and contralateral white matter (mean ± SD 799 ± 40 ms; p < 0.001). MRF T2 relaxation times were longer for meningioma (mean ± SD 69 ± 27 ms) as compared to thalamus (mean ± SD 27 ± 3 ms; p < 0.001), caudate head (mean ± SD 39 ± 5 ms; p < 0.001) and contralateral white matter (mean ± SD 35 ± 4 ms; p < 0.001) Conclusions Phantom measurements indicate that the proposed 3D-MRF sequence relaxometry estimations are valid and reproducible. For in vivo, entire brain coverage was obtained in clinically feasible time and allows quantitative assessment of meningioma in clinical practice.

scholarly journals Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Adrien Cogo ◽  
Gabrielle Mangin ◽  
Benjamin Maïer ◽  
Jacques Callebert ◽  
Mikael Mazighi ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Artery ◽  
Quinolinic Acid ◽  
Neuronal Death ◽  
Artery Occlusion ◽  
Serum Biomarkers ◽  
Diabetic Mice ◽  
Stroke Patients ◽  
Cerebral Artery Occlusion

Abstract Background Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes. Methods Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient’s serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later. Results We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients. Conclusions we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.

scholarly journals Leukocyte-Endothelium Interactions during Permanent Focal Cerebral Ischemia in Mice

2004 ◽  
Vol 24 (6) ◽  
pp. 668-676 ◽  
Author(s):  
Hiroharu Kataoka ◽  
Seong-Woong Kim ◽  
Nikolaus Plesnila
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Focal Cerebral Ischemia ◽  
Fluorescent Microscopy ◽  
Capillary Density ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
Adherent Leukocytes

The contribution of leukocyte infiltration to brain damage after permanent focal cerebral ischemia and the underlying molecular mechanisms are still unclear. Therefore, the aim of this study was to establish a mouse model for the visualization of leukocytes in the cerebral microcirculation in vivo and to investigate leukocyte-endothelial interaction (LEI) after permanent middle cerebral artery occlusion (MCAO). Sham-operated 129/Sv mice showed physiologic LEI in pial venules as observed by intravital fluorescent microscopy. Permanent focal cerebral ischemia induced a significant increase of LEI predominantly in pial venules. The number of rolling and adherent leukocytes reached 36.5 ± 13.2/100 μm × min and 22.5 ± 7.9/100 μm × min, respectively at 120 minutes after MCAO ( P = 0.016 vs. control). Of note, rolling and adherent leukocytes were also observed in arterioles of ischemic animals (7.3 ± 3.0/100 μm × min rolling and 3.0 ± 3.6/100 μm × min adherent). Capillary density was not different between groups. These results demonstrate that leukocytes accumulate in the brain not only after transient but also after permanent focal cerebral ischemia and may therefore contribute to brain damage after stroke without reperfusion.

scholarly journals Neuronal Activation of NF-κB Contributes to Cell Death in Cerebral Ischemia

2005 ◽  
Vol 25 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Wen Zhang ◽  
Ioana Potrovita ◽  
Victoria Tarabin ◽  
Oliver Herrmann ◽  
Verena Beer ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Transcriptional Control ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Neuron Specific Enolase ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

The transcription factor NF-κB is a key regulator of inflammation and cell survival. NF-κB is activated by cerebral ischemia in neurons and glia, but its function is controversial. To inhibit NF-κB selectively in neurons and glial cells, we have generated transgenic mice that express the IκBα superrepressor (IκBα mutated at serine-32 and serine-36, IκBα-SR) under transcriptional control of the neuron-specific enolase (NSE) and the glial fibrillary acidic protein (GFAP) promoter, respectively. In primary cortical neurons of NSE-IκBα-SR mice, NF-κB activity was partially inhibited. To assess NF-κB activity in vivo after permanent middle cerebral artery occlusion (MCAO), we measured the expression of NF-κB target genes by real-time polymerase chain reaction (PCR). The induction of c-myc and transforming growth factor-β2 by cerebral ischemia was inhibited by neuronal expression of IκBα-SR, whereas induction of GFAP by MCAO was reduced by astrocytic expression of IκBα-SR. Neuronal, but not astrocytic, expression of the NF-κB inhibitor reduced both infarct size and cell death 48 hours after permanent MCAO. In summary, the data show that NF-κB is activated in neurons and astrocytes during cerebral ischemia and that NF-κB activation in neurons contributes to the ischemic damage.

Sign in / Sign up

Export Citation Format

Share Document