Brain ischemia | EPFL Graph Search

Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage. Ischemia leads to alterations in brain metabolism, reduction in metabolic rates, and energy crisis. There are two types of ischemia: focal ischemia, which is confined to a specific region of the brain; and global ischemia, which encompasses wide areas of brain tissue. The main symptoms of brain ischemia involve impairments in vision, body movement, and speaking. The causes of brain ischemia vary from sickle cell anemia to congenital heart defects. Symptoms of brain ischemia can include unconsciousness, blindness, problems with coordination, and weakness in the body. Other effects that may result from brain ischemia are stroke, cardiorespiratory ar

Data-driven whole mouse brain modeling for multi-scale simulations

Dimitri Bruno Marie Rodarie

In this thesis, we present a data-driven iterative pipeline to generate, simulate and validate point-neuron models of the whole mouse brain. The ultimate goal is to replicate close loop experiments with a virtual body in a virtual world. This pipeline was origi-nally created by a PhD student of the Blue Brain Project and this pioneer work has yielded the first versions of the model and their simulations. My objective is to refine, extend and consolidate the previous version of the workflow and in particular to extend the repertoire of neuron types by integrating and consolidating available literature data.The pipeline has four main parts. First, we define a pair of reference atlases to create a spatial reference for every dataset that we want to integrate. Second, we create a cell atlas with estimates of the number and density of the major cell types in each brain region. Then, we build a connectivity atlas that describes the connections of each neuron of the mouse brain and their properties. Finally, we assign point-neuron parameters to each of the neuron types, and synaptic parameters to each of the connection types of our model to obtain a point-neuron network of the mouse brain. This network can be simulated to perform mouse brain experi-ments in-silico.In this thesis, we evaluate the quality of the different reference atlases, released by the Allen Institute for Brain Science and pro-vide methods to mitigate the impact of artifacts in the original images. We further extend the cell atlas with density estimates of more inhibitory neuron types. To do so, we introduce a new method to combine estimates of inhibitory neuron counts from the literature into a consistent framework. We also estimate inhibitory neuron density in regions where no literature data are avai-lable, using collected literature estimates and gene expression data from in situ hybridization image stacks. Our approach can be further extended to other cell types and provides a resource to build more detailed circuits of the mouse brain. Next, we refine the connectivity atlas, including literature findings on short-range connectivity. Additionally, we construct a database to store data collected on neuron types point-neuron parameters and synaptic parameters. With the results of the previous steps, we generate a new version of the whole mouse brain point-neuron network. We tested this new model against its previous version using three benchmark experiments. We explore the possibility to embed and connect detailed circuit reconstructions of the mouse brain to our point neuron model and co-simulate them. Finally, we constrain a 3D skeleton model of the mouse with joint constraints from the literature and attach muscle to its bones to create a musculoskeletal model of the mouse body that can be simulated in close-loop with our model to reproduce motor control experiments.

EPFL2022

New Evidence of Neuroprotection by Lactate after Transient Focal Cerebral Ischaemia: Extended Benefit after Intracerebroventricular Injection and Efficacy of Intravenous Administration

Ximena Castillo, Pierre Magistretti

Background: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Methods: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 mu l of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 mu mol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Results: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p

Karger2012

Non-invasive diagnostic biomarkers for estimating the onset time of permanent cerebral ischemia

Corinne Benakis, Lara Buscemi Estefanell, Rolf Gruetter, Hongxia Lei, Lijing Xin

The treatments for ischemic stroke can only be administered in a narrow time-window. However, the ischemia onset time is unknown in ~30% of stroke patients (wake-up strokes). The objective of this study was to determine whether MR spectra of ischemic brains might allow the precise estimation of cerebral ischemia onset time. We modeled ischemic stroke in male ICR-CD1 mice using a permanent middle cerebral artery filament occlusion model with laser Doppler control of the regional cerebral blood flow. Mice were then subjected to repeated MRS measurements of ipsilateral striatum at 14.1[thinsp]T. A striking initial increase in [gamma]-aminobutyric acid (GABA) and no increase in glutamine were observed. A steady decline was observed for taurine (Tau), N-acetyl-aspartate (NAA) and similarly for the sum of NAA+Tau+glutamate that mimicked an exponential function. The estimation of the time of onset of permanent ischemia within 6[thinsp]hours in a blinded experiment with mice showed an accuracy of 33[plusmn]10[thinsp]minutes. A plot of GABA, Tau, and neuronal marker concentrations against the ratio of acetate/NAA allowed precise separation of mice whose ischemia onset lay within arbitrarily chosen time-windows. We conclude that 1H-MRS has the potential to detect the clinically relevant time of onset of ischemic stroke.

Nature Publishing Group2014

Data-driven whole mouse brain modeling for multi-scale simulations

Dimitri Bruno Marie Rodarie

EPFL2022