MACT (Mosaicism with AAV Mediated Conditional Transgenesis) for Single Neuron Analysis of Neurodegeneration in Vivo, a Proof of Principle in Focal Cerebral Ischemia

2016 ◽  
Author(s):  
Madison Wynne El-Saadi ◽  
Laura Rivers ◽  
Xinli Tian ◽  
Hong Sun ◽  
Xiao-Hong Lu
Keyword(s):  
Cerebral Ischemia ◽  
Single Neuron ◽  
Focal Cerebral Ischemia ◽  
Proof Of Principle

scholarly journals Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

2005 ◽  
Vol 2 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Masamitsu Shimazawa ◽  
Satomi Chikamatsu ◽  
Nobutaka Morimoto ◽  
Satoshi Mishima ◽  
Hiroichi Nagai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Folk Medicine ◽  
Neuroprotective Function ◽  
Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

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.

Detection of apoptosis in a rat model of focal cerebral ischemia using a homing peptide selected from in vivo phage display

2008 ◽  
Vol 131 (3) ◽  
pp. 167-172 ◽  
Author(s):  
Hai-Yan Hong ◽  
Jung Sook Choi ◽  
Yoon Jung Kim ◽  
Hwa Young Lee ◽  
Wonjung Kwak ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Phage Display ◽  
Rat Model ◽  
Focal Cerebral Ischemia ◽  
Homing Peptide ◽  
In Vivo Phage Display

scholarly journals In vivo imaging of activated microglia in a mouse model of focal cerebral ischemia by two-photon microscopy

2015 ◽  
Vol 6 (9) ◽  
pp. 3303 ◽  
Author(s):  
Seoyeon Bok ◽  
Taejun Wang ◽  
Chan-Ju Lee ◽  
Seong-Uk Jeon ◽  
Young-Eun Kim ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Mouse Model ◽  
In Vivo Imaging ◽  
Focal Cerebral Ischemia ◽  
Activated Microglia ◽  
Two Photon Microscopy ◽  
Two Photon

scholarly journals The Rapid Decrease in Astrocyte-Associated Dystroglycan Expression by Focal Cerebral Ischemia is Protease-Dependent

2007 ◽  
Vol 28 (4) ◽  
pp. 812-823 ◽  
Author(s):  
Richard Milner ◽  
Stephanie Hung ◽  
Xiaoyun Wang ◽  
Maria Spatz ◽  
Gregory J del Zoppo
Keyword(s):  
Cerebral Ischemia ◽  
Basal Lamina ◽  
Focal Cerebral Ischemia ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Receptor Expression ◽  
Cerebral Microvessels ◽  
The Impact

During focal cerebral ischemia, the detachment of astrocytes from the microvascular basal lamina is not completely explained by known integrin receptor expression changes. Here, the impact of experimental ischemia (oxygen—glucose deprivation (OGD)) on dystroglycan expression by murine endothelial cells and astrocytes grown on vascular matrix laminin, perlecan, or collagen and the impact of middle cerebral artery occlusion on αβ-dystroglycan within cerebral microvessels of the nonhuman primate were examined. Dystroglycan was expressed on all cerebral microvessels in cortical gray and white matter, and the striatum. Astrocyte adhesion to basal lamina proteins was managed in part by α-dystroglycan, while ischemia significantly reduced expression of dystroglycan both in vivo and in vitro. Furthermore, dystroglycan and integrin α6β4 expressions on astrocyte end-feet decreased in parallel both in vivo and in vitro. The rapid loss of astrocyte dystroglycan during OGD appears protease-dependent, involving an matrix metalloproteinase-like activity. This may explain the rapid detachment of astrocytes from the microvascular basal lamina during ischemic injury, which could contribute to significant changes in microvascular integrity.

scholarly journals PET Imaging of Serotoninergic Neurotransmission with [11C]DASB and [18F]altanserin after Focal Cerebral Ischemia in Rats

2013 ◽  
Vol 33 (12) ◽  
pp. 1967-1975 ◽  
Author(s):  
Abraham Martín ◽  
Boguslaw Szczupak ◽  
Vanessa Gómez-Vallejo ◽  
Sandra Plaza ◽  
Daniel Padró ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Functional Recovery ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Focal Cerebral Ischemia ◽  
Recovery Process ◽  
Artery Occlusion ◽  
Functional Improvement ◽  
Binding Potential ◽  
Positron Emission

The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [11C]DASB and [18F]altanserin at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with [11C]DASB and [18F]altanserin showed a dramatic decline in serotonin transporter (SERT) and 5-HT2A binding potential in the cortex and striatum after cerebral ischemia. Interestingly, a slight increase in [11C]DASB binding was observed from days 7 to 21 followed by the uppermost binding at day 28 in the ipsilateral midbrain. In contrast, no changes were observed in the contralateral hemisphere by using both radiotracers. Likewise, both functional and behavior testing showed major impaired outcome at day 1 after ischemia onset followed by a recovery of the sensorimotor function and dexterity from day 21 to day 28 after cerebral ischemia. Taken together, these results might evidence that SERT changes in the midbrain could have a key role in the functional recovery process after cerebral ischemia.

scholarly journals Blocking TLR2 in vivo Protects against Accumulation of Inflammatory Cells and Neuronal Injury in Experimental Stroke

2010 ◽  
Vol 31 (2) ◽  
pp. 757-766 ◽  
Author(s):  
Gina Ziegler ◽  
Dorette Freyer ◽  
Denise Harhausen ◽  
Uldus Khojasteh ◽  
Wilfried Nietfeld ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Focal Cerebral Ischemia ◽  
Neuronal Survival ◽  
Inflammatory Cells ◽  
Experimental Stroke ◽  
Wild Type ◽  
Antibody Treatment ◽  
Cell Counts

Reduced infarct volume in TLR2-knockout mice compared with C57Bl/6 wild-type mice has recently been shown in experimental stroke and confirmed in this study. We now also show a significant decrease of CD11b-positive cell counts and decreased neuronal death in the ischemic hemispheres of TLR2-deficient mice compared with C57Bl/6wt mice 2 days after transient focal cerebral ischemia. To examine the potential benefit of intravascular TLR2 inhibition, C57Bl/6wt mice were treated intraarterially with TLR2-blocking anti-TLR2 antibody (clone T2.5) after 45 minutes of cerebral ischemia and compared with control antibody (isotype) treated wild-type mice. Whereas T2.5-treated mice had no reduction in infarct volumes at 48 hours after reperfusion, they did have decreased numbers of CD11b-positive inflammatory cells and decreased neuronal death compared with isotype-treated control mice. Comparison of the isotype antibody treatment to control (saline) treatment showed no effects on infarct volumes or neuronal survival. However, mice treated with the control isotype antibody had increased numbers of CD11b-positive inflammatory cells compared with saline-treated animals. Thus, antibody treatment itself (i.e., control isotype antibody, but potentially of any antibody) may have adverse effects and limit therapeutic benefit of anti-TLR2-antibody therapy. We conclude that TLR2 mediates leukocyte and microglial infiltration and neuronal death, which can be attenuated by TLR2 inhibition. The TLR2 inhibition in vivo improves neuronal survival and may represent a future stroke therapy.

Sign in / Sign up

Export Citation Format

Share Document