modeling-stroke-mice-permanent-coagulation-distal-middle-cerebral

Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery

Stroke is the third most common cause of death and a main cause of acquired adult disability in developed countries. Only very limited therapeutical ...

modeling-stroke-in-mice-focal-cortical-lesions-by-photothrombosis

Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis

Stroke is a leading cause of death and acquired adult disability in developed countries. Despite extensive investigation for novel therapeutic strategies, ...

modeling-stroke-mice-transient-middle-cerebral-artery-occlusion-via

Modeling Stroke in Mice: Transient Middle Cerebral Artery Occlusion via the External Carotid Artery

Stroke is the third most common cause of mortality and the leading cause of acquired adult disability in developed countries. To date, therapeutic options ...

University Hospital Munich

Munich Cluster for Systems Neurology (SyNergy)

LMU Munich

Understanding the evolution of neonatal hypoxic/ischemic is essential for novel neuroprotective approaches. We describe the neuropathology and glial/inflammatory response, from 3 hours to 100 days, after carotid occlusion and hypoxia (8% O(2), 55 minutes) to the C57/BL6 P7 mouse. Massive tissue injury and atrophy in the ipsilateral (IL) hippocampus, corpus callosum, and caudate-putamen are consistently shown. Astrogliosis peaks at 14 days, but glial scar is still evident at day 100. Microgliosis peaks at 3-7 days and decreases by day 14. Both glial responses start at 3 hours in the corpus callosum and hippocampal fissure, to progressively cover the degenerating CA field. Neutrophils increase in the ventricles and hippocampal vasculature, showing also parenchymal extravasation at 7 days. Remarkably, delayed milder atrophy is also seen in the contralateral (CL) hippocampus and corpus callosum, areas showing astrogliosis and microgliosis during the first 72 hours. This detailed and long-term cellular response characterization of the ipsilateral and contralateral hemisphere after H/I may help in the design of better therapeutic strategies.

Short and long-term analysis and comparison of neurodegeneration and inflammatory cell response in the ipsilateral and contralateral hemisphere of the neonatal mouse brain after hypoxia/ischemia.

Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer's disease (AD) progression. However, the mechanisms of microbiome-brain interaction in AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice increased the Aβ plaque load to levels of conventionally colonized (specific pathogen-free [SPF]) animals and SCFA supplementation to SPF mice even further exacerbated plaque load. This was accompanied by the pronounced alterations in microglial transcriptomic profile, including upregulation of ApoE. Despite increased microglial recruitment to Aβ plaques upon SCFA supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that microbiota-derived SCFA are critical mediators along the gut-brain axis which promote Aβ deposition likely via modulation of the microglial phenotype.

Gemma Llovera

Institute for Stroke and Dementia Research

University Hospital Munich

Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery

Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis

Modeling Stroke in Mice: Transient Middle Cerebral Artery Occlusion via the External Carotid Artery

Gemma Llovera

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Institute for Stroke and Dementia Research

University Hospital Munich

Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery

Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis

Modeling Stroke in Mice: Transient Middle Cerebral Artery Occlusion via the External Carotid Artery

Institute for Stroke and Dementia Research