Neuroprotective effects of lactate and ketone bodies in acute brain injury.

The goal of neurocritical care is to prevent and reverse the pathologic cascades of secondary brain injury by optimizing cerebral blood flow, oxygen supply and substrate delivery. While glucose is an essential energetic substrate for the brain, we frequently observe a strong decrease in glucose delivery and/or a glucose metabolic dysregulation following acute brain injury. In parallel, during the last decades, lactate and ketone bodies have been identified as potential alternative fuels to provide energy to the brain, both under physiological conditions and in case of glucose shortage. They are now viewed as integral parts of brain metabolism. In addition to their energetic role, experimental evidence also supports their neuroprotective properties after acute brain injury, regulating in particular intracranial pressure control, decreasing ischemic volume, and leading to an improvement in cognitive functions as well as survival. In this review, we present preclinical and clinical evidence exploring the mechanisms underlying their neuroprotective effects and identify research priorities for promoting lactate and ketone bodies use in brain injury.

[Neurology: what's new in 2023]. / Neurologie: ce qui a changé en 2023.

The year 2023 is marked by the arrival on the market of lecanemab for the treatment of Alzheimer's disease. New biomarkers have demonstrated their usefulness in monitoring peripheral neuropathies and diagnosing synucleinopathies. A genetic study has highlighted the role of nervous system cells in the risk of progression of multiple sclerosis (MS). The adverse effects of anticonvulsant treatments after prenatal exposure and on lipid metabolism have been clarified. New anti-CGRP treatments have demonstrated their efficacy in migraine attacks and chronic migraines. The criteria for thrombectomy have been further broadened. And finally, rehabilitation is refining the management of cerebrovascular patients and those with secondary progressive MS.

L'année 2023 est marquée par l'arrivée sur le marché du lécanémab pour le traitement de la maladie d'Alzheimer. De nouveaux biomarqueurs ont démontré leur utilité dans le suivi des neuropathies périphériques ou dans le diagnostic des synucléinopathies. Une étude génétique a mis en évidence le rôle des cellules du système nerveux dans le risque de progression de la sclérose en plaques (SEP). Les effets indésirables des traitements anticonvulsivants lors d'exposition prénatale ou sur le métabolisme des lipides ont été précisés. De nouveaux traitements anti-CGRP ont démontré leur efficacité dans les crises migraineuses et les migraines chroniques. Les critères de thrombectomie se sont encore élargis. Et enfin, la réhabilitation affine la prise en charge des patients cérébrovasculaires et de ceux atteints d'une SEP secondaire progressive.

Influence of DNP Polarizing Agents on Biochemical Processes: TEMPOL in Transient Ischemic Stroke.

Hyperpolarization of 13C by dissolution dynamic nuclear polarization (dDNP) boosts the sensitivity of magnetic resonance spectroscopy (MRS), making possible the monitoring in vivo and in real time of the biochemical reactions of exogenously infused 13C-labeled metabolic tracers. The preparation of a hyperpolarized substrate requires the use of free radicals as polarizing agents. Although added at very low doses, these radicals are not biologically inert. Here, we demonstrate that the presence of the nitroxyl radical TEMPOL influences significantly the cerebral metabolic readouts of a hyperpolarized [1-13C] lactate bolus injection in a mouse model of ischemic stroke with reperfusion. Thus, the choice of the polarizing agent in the design of dDNP hyperpolarized MRS experiments is of great importance and should be taken into account to prevent or to consider significant effects that could act as confounding factors.

[Neurology: what's new in 2022]. / Neurologie : ce qui a changé en 2022.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies.

L'année 2022 a été marquée par l'arrivée de nombreux traitements pour la myasthénie réfractaire. Le lien entre l'épilepsie et le risque cérébro-vasculaire a été bien étudié, démontrant que la lamotrigine semble être le meilleur traitement pour prévenir la mortalité chez les patients de 45 ans et plus. De nouvelles études ont enfin pu établir l'utilité de la thrombectomie dans les occlusions basilaires. Le lien entre le virus d'Epstein-Barr et la sclérose en plaques a pu être prouvé à la suite d'une importante étude de cohorte. Une nouvelle technique d'administration sous-cutanée de la lévodopa semble prometteuse. Enfin, de nombreuses études confirment l'efficacité et l'excellente tolérance des anticorps anti-CGRP (Calcitonine Gene Related Protein).

Carotid plaque surface echogenicity predicts cerebrovascular events: An Echographic Multicentric Swiss Study.

BACKGROUND AND PURPOSE: To determine the prognostic value for ischemic stroke or transitory ischemic attack (TIA) of plaque surface echogenicity alone or combined to degree of stenosis in a Swiss multicenter cohort METHODS: Patients with ≥60% asymptomatic or ≥50% symptomatic carotid stenosis were included. Grey-scale based colour mapping was obtained of the whole plaque and of its surface defined as the regions between the lumen and respectively 0-0.5, 0-1, 0-1.5, and 0-2 mm of the outer border of the plaque. Red, yellow and green colour represented low, intermediate or high echogenicity. Proportion of red color on surface (PRCS) reflecting low echogenictiy was considered alone or combined to degree of stenosis (Risk index, RI). RESULTS: We included 205 asymptomatic and 54 symptomatic patients. During follow-up (median/mean 24/27.7 months) 27 patients experienced stroke or TIA. In the asymptomatic group, RI ≥0.25 and PRCS ≥79% predicted stroke or TIA with a hazard ratio (HR) of respectively 8.7 p = 0.0001 and 10.2 p < 0.0001. In the symptomatic group RI ≥0.25 and PRCS ≥81% predicted stroke or TIA occurrence with a HR of respectively 6.1 p = 0.006 and 8.9 p = 0.001. The best surface parameter was located at 0-0.5mm. Among variables including age, sex, degree of stenosis, stenosis progression, RI, PRCS, grey median scale values and clinical baseline status, only PRCS independently prognosticated stroke (p = 0.005). CONCLUSION: In this pilot study including patients with at least moderate degree of carotid stenosis, PRCS (0-0.5mm) alone or combined to degree of stenosis strongly predicted occurrence of subsequent cerebrovascular events.

Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation.

Lactate can protect against damage caused by acute brain injuries both in rodents and in human patients. Besides its role as a metabolic support and alleged preferred neuronal fuel in stressful situations, an additional signaling mechanism mediated by the hydroxycarboxylic acid receptor 1 (HCAR1) was proposed to account for lactate's beneficial effects. However, the administration of HCAR1 agonists to mice subjected to middle cerebral artery occlusion (MCAO) at reperfusion did not appear to exert any relevant protective effect. To further evaluate the involvement of HCAR1 in the protection against ischemic damage, we looked at the effect of HCAR1 absence. We subjected wild-type and HCAR1 KO mice to transient MCAO followed by treatment with either vehicle or lactate. In the absence of HCAR1, the ischemic damage inflicted by MCAO was less pronounced, with smaller lesions and a better behavioral outcome than in wild-type mice. The lower susceptibility of HCAR1 KO mice to ischemic injury suggests that lactate-mediated protection is not achieved or enhanced by HCAR1 activation, but rather attributable to its metabolic effects or related to other signaling pathways. Additionally, in light of these results, we would disregard HCAR1 activation as an interesting therapeutic strategy for stroke patients.

[Neurology : what's new in 2021]. / Neurologie.

In 2021, we assisted to the publication of new diagnostic criteria, classifications, and guidelines (CIDP, brain tumors, auto-immune encephalitis). Several studies helped to define the pharmacological management of focal and generalized epileptic seizures and epilepsy in pregnant women. The availability of biomarkers and the approval of immunotherapies are modifying the landscape of dementia management. Endovascular interventions without previous thrombolysis seems to be effective in anterior circulation acute ischemic stroke (AIS) and severe posterior circulation AIS. Neurologic complications of Sars-CoV-2 infection were further studied, as well as the efficacy of vaccines in immunosuppressed patients. New molecules and techniques show promising results for the treatment of migraine and cluster headache.

L'année 2021 a été marquée par la publication des nouveaux critères diagnostiques, classifications et guidelines (polyradiculonévrite inflammatoire démyélinisante chronique, tumeurs cérébrales, encéphalites autoimmunes). L'attitude thérapeutique dans les épilepsies focales ou généralisées et l'épilepsie chez la femme enceinte a été mieux définie. Les marqueurs biologiques et les immunothérapies modifient le paysage de la prise en charge des démences. Le traitement endovasculaire des AVC de la circulation antérieure semble efficace indépendamment d'une thrombolyse préalable, ainsi qu'en cas d'AVC sévère de la circulation postérieure. Les complications neurologiques du SARS-CoV-2 ont été éclaircies et l'efficacité des vaccins étudiée chez les patients immunosupprimés. Plusieurs nouvelles molécules et techniques montrent des résultats prometteurs pour les migraines et céphalées en grappe.

Intima-Media Thickness and Pulsatility Index of Common Carotid Arteries in Acute Ischaemic Stroke Patients with Diabetes Mellitus.

Ultrasonographic parameters such as the common carotid artery (CCA) pulsatility index (PI) and CCA intima-media thickness (IMT) have been associated with an increased mortality and risk of recurrent stroke, respectively. We hypothesized that these ultrasonographic parameters may be useful for monitoring diabetic patients after an acute stroke. We analysed retrospective data of consecutive acute ischaemic stroke patients from the ASTRAL registry who underwent pre-cerebral ultrasonographic evaluation within 7 days of symptom onset. We compared clinical, demographic, radiological and ultrasonographic parameters in diabetic versus non-diabetic patients (univariable and multivariable analyses) and the association of these parameters with CCA PI and CCA IMT. We analysed 1507 carotid duplex ultrasound examinations from patients with a median age of 74 years. Cardiovascular co-morbidities, including hypertension, hypercholesterolemia, obstructive sleep apnoea syndrome, higher body-mass index (BMI) and peripheral artery disease, were associated with diabetes mellitus (DM). Diabetics were more often under antiplatelet therapy and had atrial fibrillation at admission. Diabetic patients showed an increased CCA PI and IMT in line with more atherosclerotic changes on acute CTA compared to non-diabetic patients. Taking IMT as the dependent variable in a second analysis, DM, higher age, hypertension, smoking and CCA PI were associated with higher IMT. Taking CCA PI as the dependent variable in a third analysis, DM, higher age and higher NIHSS at admission were associated with higher CCA PI values. Increased IMT was also associated with higher PI. We show that CCA PI and IMT are higher in diabetic patients in the first week after an initial stroke.

Preconditioning by Preceding Ischemic Cerebrovascular Events.

Background Emerging yet contrasting evidence from animal and human studies associates ischemic preconditioning with improvement of subsequent stroke severity, although long-term outcome remains unclear. The purpose of this study was to analyze how preceding cerebral ischemic events influence subsequent stroke severity and outcome. Methods and Results Data for this retrospective cohort study were extracted from ASTRAL (Acute Stroke Registry and Analysis of Lausanne). This registry includes a sample of all consecutive patients with acute ischemic strokes admitted to the stroke unit and/or intensive care unit of the Lausanne University Hospital, Switzerland. We investigated associations between preceding ischemic events (transient ischemic attacks or ischemic strokes) and the impact on subsequent stroke severity and clinical improvement within 24 hours, measured through National Institute of Health Stroke Scale, as well as 3-month outcome, determined through a shift in the modified Rankin Scale. Of 3530 consecutive patients with ischemic stroke (43% women, median age 73 years), 1001 (28%) had ≥1 preceding cerebral ischemic events (45% transient ischemic attack, 55% ischemic stroke; 31% multiple events). After adjusting for multiple prehospital, clinical, and laboratory confounders, admission stroke severity was significantly lower in patients preconditioned through a preceding ischemic event, but 24-hour improvement was not significant and 3-month outcome was unfavorable. Conclusions Preceding ischemic events were independently associated with a significant reduction in subsequent stroke severity but worsened long-term clinical outcome. These results, if confirmed by future randomized studies, may help design neuroprotective strategies. The unfavorable effect on stroke outcome is probably a consequence of the cumulative disability burden after multiple ischemic events.

Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion.

Lactate is an intriguing molecule with emerging physiological roles in the brain. It has beneficial effects in animal models of acute brain injuries and traumatic brain injury or subarachnoid hemorrhage patients. However, the mechanism by which lactate provides protection is unclear. While there is evidence of a metabolic effect of lactate providing energy to deprived neurons, it can also activate the hydroxycarboxylic acid receptor 1 (HCAR1), a Gi-coupled protein receptor that modulates neuronal firing rates. After cerebral hypoxia-ischemia, endogenously produced brain lactate is largely increased, and the exogenous administration of more lactate can decrease lesion size and ameliorate the neurological outcome. To test whether HCAR1 plays a role in lactate-induced neuroprotection, we injected the agonists 3-chloro-5-hydroxybenzoic acid and 3,5-dihydroxybenzoic acid into mice subjected to 30-min middle cerebral artery occlusion. The in vivo administration of HCAR1 agonists at reperfusion did not appear to exert any relevant protective effect as seen with lactate administration. Our results suggest that the protective effects of lactate after hypoxia-ischemia come rather from the metabolic effects of lactate than its signaling through HCAR1.

[COVID-19 and stroke: associated or not ?] / Covid-19 et AVC: associés ou non ?

COVID-19 patients are at a higher risk of stroke. This observation is in apparent contradiction with the reduced number of stroke patient admissions during the first wave of the COVID-19 pandemic, seen worldwide. The SARS-CoV-2 can affect the endothelium, favour a procoagulant state and involves the heart, leading to an increased risk of developing a stroke. The pandemic and confinement influence the behaviour of the population, perhaps more reticent to contact emergency departments flooded with COVID-19 patients and likely to have modified levels of stress. In addition, it was shown that confinement during the pandemic reduced air pollution, thought to affect stroke risk. These indirect effects of SARS-CoV-2 probably also impact the number of hospital admissions for stroke. These different aspects are presented here as a controversy.

Les patients souffrant de Covid-19 ont un risque nettement augmenté de développer un AVC. Cette constatation est en apparente contradiction avec la diminution du nombre d'hospitalisations pour AVC observée au niveau mondial depuis le début de la pandémie. L'infection à SARS-CoV-2 peut toucher l'endothélium, favoriser un état procoagulant et affecter le cœur, conduisant à une augmentation du risque d'AVC. Les effets indirects de la pandémie et du confinement sur le comportement de la population, peut-être réticente à consulter les urgences, surchargées par l'afflux de patients Covid-19, sur le stress et sur la pollution atmosphérique influencent probablement aussi le nombre d'hospitalisations pour AVC. Ces différents aspects sont présentés ici sous forme de controverse.

[Recent Advances in Neurology]. / Neurologie.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease.

L'année 2020 a vu d'importantes avancées dans le domaine des biomarqueurs sanguins pour le diagnostic biologique de la maladie d'Alzheimer. Plusieurs études permettent de mieux définir la prise en charge de l'épilepsie chez la femme en âge de procréer et de l'état de mal épileptique. Les nouvelles recommandations suisses pour la prise en charge préhospitalière de l'AVC aigu sont en cours de publication, tout comme de nouvelles cibles pour leur prévention secondaire. De nombreuses avancées concernant la prise en charge des Neuromyelitis Optica Spectrum Disorder ont été publiées. Divers tableaux neurologiques (centraux et périphériques) liés à la pandémie de Covid-19 ont été décrits. Plusieurs études ont permis de confirmer l'efficacité des nouveaux traitements de la migraine (notamment les anti-Calcitonin Gene-Related Peptide). Enfin, de nouvelles thérapies pharmacologiques sont disponibles pour la maladie de Parkinson.

Predictors of the pulsatility index in the middle cerebral artery of acute stroke patients.

Cervical and transcranial Doppler (TCD) are widely used as non-invasive methods in the evaluation of acute ischemic stroke (AIS) patients. High-grade carotid artery stenosis induces haemodynamic changes such as collateral flow and a so-called post-stenotic flow pattern of the middle cerebral artery (MCA), which appears flattened, with a reduction of the velocity difference between systole and diastole. We studied the influence of carotid artery stenosis and other variables on the flow pattern in the MCA using the pulsatility index (PI), a quantitative TCD parameter reflecting the flow spectrum in a large of cohort AIS patients. We performed ultrasound examinations of 1825 AIS patients at the CHUV from October 2004 to December 2014. We extracted patient characteristics from the ASTRAL registry. Carotid stenosis severity was classified as < 50%, 50-70%, 70-90% and > 90%, or occlusion, according to Doppler velocity criteria. We first determined variables associated with stenosis grade. Then we performed a multivariate analysis after adjusting for baseline differences, using MCA PI as dependent variable. Carotid stenosis > 70% (- 0.07) and carotid stenosis > 90%, or occlusion (- 0.14) and left side (- 0.02) are associated with lower MCA PI values. Age (+0.006 PI units per decade), diabetes (+0.07), acute ischemic changes on initial CT (+0.03) and severe plaque morphology (+0.18) are associated with higher MCA PI values. We found a number of clinical and radiological conditions that significantly influence the PI of the MCA, including high-grade ipsilateral carotid stenosis in AIS patients. We provide for the first time a quantitative evaluation of the effect of these influencing factors from a large cohort of AIS patients.

Caveolin-1 Regulates Perivascular Aquaporin-4 Expression After Cerebral Ischemia.

Edema is a hallmark of many brain disorders including stroke. During vasogenic edema, blood-brain barrier (BBB) permeability increases, contributing to the entry of plasma proteins followed by water. Caveolae and caveolin-1 (Cav-1) are involved in these BBB permeability changes. The expression of the aquaporin-4 (AQP4) water channel relates to brain swelling, however, its regulation is poorly understood. Here we tested whether Cav-1 regulates AQP4 expression in the perivascular region after brain ischemia in mice. We showed that Cav-1 knockout mice had enhanced hemispheric swelling and decreased perivascular AQP4 expression in perilesional and contralateral cortical regions compared to wild-type. Glial fibrillary acidic protein-positive astrocytes displayed less branching and ramification in Cav-1 knockout mice compared to wild-type animals. There was a positive correlation between the area of perivascular AQP4-immunolabelling and branch length of Glial fibrillary acidic protein-positive astrocytes in wild-type mice, not seen in Cav-1 knockout mice. In summary, we show for the first time that loss of Cav-1 results in decreased AQP4 expression and impaired perivascular AQP4 covering after cerebral ischemia associated with altered reactive astrocyte morphology and enhanced brain swelling. Therapeutic approaches targeting Cav-1 may provide new opportunities for improving stroke outcome. SIGNIFICANCE STATEMENT: Severe brain edema worsens outcome in stroke patients. Available treatments for stroke-related edema are not efficient and molecular and cellular mechanisms are poorly understood. Cellular water channels, aquaporins (AQPs), are mainly expressed in astrocytes in the brain and play a key role in water movements and cerebral edema, while endothelial caveolins have been suggested to play a role in vasogenic edema. Here we used an integrative approach to study possible interaction between AQP4 and caveolin-1 (Cav-1) after stroke. Absence of Cav-1 was associated with perivascular changes in AQP4 expression and enhanced brain swelling at 3 days after cerebral ischemia. The present work indicates a direct or indirect effect of Cav-1 on perivascular AQP4, which may lead to novel edema therapy.

Evaluating the potential of hyperpolarised [1-13C] L-lactate as a neuroprotectant metabolic biosensor for stroke.

Cerebral metabolism, which can be monitored by magnetic resonance spectroscopy (MRS), changes rapidly after brain ischaemic injury. Hyperpolarisation techniques boost 13C MRS sensitivity by several orders of magnitude, thereby enabling in vivo monitoring of biochemical transformations of hyperpolarised (HP) 13C-labelled precursors with a time resolution of seconds. The exogenous administration of the metabolite L-lactate was shown to decrease lesion size and ameliorate neurological outcome in preclinical studies in rodent stroke models, as well as influencing brain metabolism in clinical pilot studies of acute brain injury patients. The aim of this study was to demonstrate the feasibility of measuring HP [1-13C] L-lactate metabolism in real-time in the mouse brain after ischaemic stroke when administered after reperfusion at a therapeutic dose. We showed a rapid, time-after-reperfusion-dependent conversion of [1-13C] L-lactate to [1-13C] pyruvate and [13C] bicarbonate that brings new insights into the neuroprotection mechanism of L-lactate. Moreover, this study paves the way for the use of HP [1-13C] L-lactate as a sensitive molecular-imaging biosensor in ischaemic stroke patients after endovascular clot removal.

[Neurology 2019]. / Neurologie.

New studies confirm the possibility of late thrombolysis. Meta-analyses have confirmed that CGRP inhibitors are efficacious for migraines. Cladribine is a new oral treatment for relapsing-remitting multiple sclerosis. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a new clinical entity accounting for cognitive decline in old patients. The timing of levodopa introduction has no effect on the long-term course of idiopathic Parkinson's disease. Hypophosphatemia helps distinguish between seizures and syncopes in the emergency department. A second course of intravenous immunoglobulins provides no benefit for severe Guillain Barre syndrome. Outdoor therapy improves clinical scales in patients with disorder of consciousness. Ultrasound guided lumbar puncture improves the yield of the procedure.

De nouvelles études confirment la possibilité de thrombolyse tardive. Les méta-analyses confirment l'effet bénéfique des inhibiteurs du CGRP (calcitonin gene-related peptide) pour la migraine. La cladribine est un nouveau traitement oral pour la sclérose en plaque de type poussée-rémission. L'encéphalopathie à TDP-43 à prédominance limbique est une nouvelle entité en lien avec des troubles cognitifs de la personne âgée. Le délai d'introduction de la lévodopa n'a pas d'influence sur l'évolution à long terme de la maladie de Parkinson. L'hypophosphatémie aide à différencier les crises d'épilepsie des syncopes. Une deuxième cure d'immunoglobulines n'apporte pas de bénéfice dans le traitement du syndrome de Guillain-Barré. Les patients avec troubles de l'état de conscience bénéficient des thérapies à l'air libre. L'ultrason améliore le rendement de la ponction lombaire.

Involvement of caveolin-1 in neurovascular unit remodeling after stroke: Effects on neovascularization and astrogliosis.

Complex cellular and molecular events occur in the neurovascular unit after stroke, such as blood-brain barrier (BBB) dysfunction and inflammation that contribute to neuronal death, neurological deterioration and mortality. Caveolin-1 (Cav-1) has distinct physiological functions such as caveolae formation associated with endocytosis and transcytosis as well as in signaling pathways. Cav-1 has been proposed to be involved in BBB dysfunction after brain injury; however, its precise role is poorly understood. The goal of this study was to characterize the expression and effect of Cav-1 deletion on outcome in the first week in a transient Middle Cerebral Artery Occlusion stroke model. We found increased Cav-1 expression in new blood vessels in the lesion and in reactive astrocytes in the peri-lesion areas. In Cav-1 KO mice, the lesion volume was larger and the behavioral outcome worse than in WT mice. Cav-1 KO mice exhibited reduced neovascularization and modified astrogliosis, without formation of a proper glial scar around the lesion at three days post injury, coinciding with aggravated outcomes. Altogether, these results point towards a potential protective role of endogenous Cav-1 in the first days after ischemia by promoting neovascularization, astrogliosis and scar formation.

Metabolic fingerprints discriminating severity of acute ischemia using in vivo high-field 1 H magnetic resonance spectroscopy.

Despite the improving imaging techniques, it remains challenging to produce magnetic resonance (MR) imaging fingerprints depicting severity of acute ischemia. The aim of this study was to evaluate the potential of the overall high-field 1 H MR Spectroscopy (1 H-MRS) neurochemical profile as a metabolic signature for acute ischemia severity in rodent brains. We modeled global ischemia with one-stage 4-vessel-occlusion (4VO) in rats. Vascular structures were assessed immediately by magnetic resonance angiography. The neurochemical responses in the bilateral cortex were measured 1 h after stroke onset by 1 H-MRS. Then we used Partial-Least-Squares discriminant analysis on the overall neurochemical profiles to seek metabolic signatures for ischemic severity subgroups. This approach was further tested on neurochemical profiles of mouse striatum 1 h after permanent middle cerebral artery occlusion, where vascular blood flow was monitored by laser Doppler. Magnetic resonance angiography identified successful 4VO from controls and incomplete global ischemia (e.g., 3VO). 1 H-MR spectra of rat cortex after 4VO showed a specific metabolic pattern, distinct from that of respective controls and rats with 3VO. Partial-Least-Squares discriminant analysis on the overall neurochemical profiles revealed metabolic signatures of acute ischemia that may be extended to mice after permanent middle cerebral artery occlusion. Fingerprinting severity of acute ischemia using neurochemical information may improve MR diagnosis in stroke patients.

Spatio-temporal overview of neuroinflammation in an experimental mouse stroke model.

After ischemic stroke, in the lesion core as well as in the ischemic penumbra, evolution of tissue damage and repair is strongly affected by neuroinflammatory events that involve activation of local specialized glial cells, release of inflammatory mediators, recruiting of systemic cells and vascular remodelling. To take advantage of this intricate response in the quest to devise new protective therapeutic strategies we need a better understanding of the territorial and temporal interplay between stroke-triggered inflammatory and cell death-inducing processes in both parenchymal and vascular brain cells. Our goal is to describe structural rearrangements and functional modifications occurring in glial and vascular cells early after an acute ischemic stroke. Low and high scale mapping of the glial activation on brain sections of mice subjected to 30 minutes middle cerebral artery occlusion (MCAO) was correlated with that of the neuronal cell death, with markers for microvascular changes and with markers for pro-inflammatory (IL-1ß) and reparative (TGFß1) cytokines. Our results illustrate a time-course of the neuroinflammatory response starting at early time-points (1 h) and up to one week after MCAO injury in mice, with an accurate spatial distribution of the observed phenomena.

[Neurology]. / Neurologie.

Thrombolysis and late thrombectomy can be performed in case of compatible radiological imaging. Anti-CGRP monoclonal antibodies seem more effective for the treatment of migraine. Siponimod can reduce significantly disability progression in secondarily progressive MS. Brand-to-generic levetiracetam switching does not cause recrudescence of epileptic seizures. A new definition of Alzheimer's disease using biomarkers of cerebrospinal fluid (CSF) and imaging provides a better understanding of the underlying mechanisms. The use of levodopa-carbidopa intestinal gel and a subcutaneous apomorphine infusion allow a reduction of motor fluctuations in Parkinson's disease. Eculizumab appears as an alternative treatment in severe forms of myasthenia gravis.

La thrombolyse et la thrombectomie tardives peuvent être effectuées en cas d'imagerie favorable. Les anticorps monoclonaux anti-CGRP semblent plus efficaces pour le traitement de la migraine. Le siponimod permet de ralentir significativement la progression du handicap dans la sclérose en plaques (SEP) secondairement progressive. L'utilisation de génériques de lévétiracétam n'engendre pas de recrudescence de crises épileptiques. Une nouvelle définition de la maladie d'Alzheimer à l'aide des biomarqueurs du liquide céphalorachidien (LCR) et d'imagerie permet une meilleure compréhension des mécanismes sous-jacents. La perfusion intestinale d'un gel de lévodopa-carbidopa et la pompe d'apomorphine diminuent les fluctuations motrices dans la maladie de Parkinson. L'éculizumab apparaît comme une alternative dans les formes sévères de myasthénie.