N-acetyl aspartate levels early after ischemic stroke accurately reflect long-term brain damage.

Background: Estimation of brain damage following an ischemic stroke is most often performed within the first few days after the insult, where large amounts of oedematous fluid have accumulated. This can potentially hamper correct measurement of infarcted area, since oedema formation poorly reflects infarct size. This study presents a non-invasive, easily applicable and reliable method to accurately predict long-term evolution and late-stage infarction.

Long-term immune cell profiling in stroke patients with or without infections.

Purpose: Infections are frequent complications in acute ischemic stroke and may be caused by an altered immune response influencing brain damage. We compared long-term immune responses in stroke patients with or without infections during the recovery period by performing a long-term profiling of clinically relevant inflammatory parameters from stroke onset until day 49.

Materials And Methods: Thirty-four stroke patients were retrospectively included and divided into two groups depending on infection status.

Staphylococcus aureus infected embolic stroke upregulates Orm1 and Cxcl2 in a rat model of septic stroke pathology.

Objective: Ischaemic brain lesions and brain abscesses are frequent in both human and animal cases of septic embolic stroke. However, existing models of brain infection do not reflect central aspects of septic embolic stroke. Our aim was to compare septic and non-septic embolic stroke in order to identify gene expressions, inflammatory mediators and brain damage in a rat model.

Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke.

Objective: In this clinical case-control study, we investigated statin treatment in stroke patients on a range of inflammatory effectors in peripheral blood. We focus on RhoA GTPase and its downstream effectors as a future inflammatory target in stroke treatment.

Methods: Data from 10 patients already on statins at stroke onset (Pre-S group) was compared with data from both 29 patients starting statin treatment right after stroke onset (Post-S group) and with 8 healthy controls.

RhoA Drives T-Cell Activation and Encephalitogenic Potential in an Animal Model of Multiple Sclerosis.

T-cells are known to be intimately involved in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). T-cell activation is controlled by a range of intracellular signaling pathways regulating cellular responses such as proliferation, cytokine production, integrin expression, and migration. These processes are crucial for the T-cells' ability to mediate inflammatory processes in autoimmune diseases such as MS.

T-cells and macrophages peak weeks after experimental stroke: Spatial and temporal characteristics.

The activities of the central and peripheral immune systems impact neurological outcome after ischemic stroke. However, studies investigating the temporal profile of leukocyte infiltration, especially T-cell recruitment, are sparse. Our aim was to investigate leukocyte infiltration at different time points after experimental stroke in mice.

Turning Microscopy in the Medical Curriculum Digital: Experiences from The Faculty of Health and Medical Sciences at University of Copenhagen.

Familiarity with the structure and composition of normal tissue and an understanding of the changes that occur during disease is pivotal to the study of the human body. For decades, microscope slides have been central to teaching pathology in medical courses and related subjects at the University of Copenhagen. Students had to learn how to use a microscope and envisage three-dimensional processes that occur in the body from two-dimensional glass slides.

Trichuris suis secrete products that reduce disease severity in a multiple sclerosis model.

Multiple sclerosis is a chronic inflammatory central nervous system (CNS) disease, which affects about 1 in 1000 individuals in the western world. It has been suggested that this relatively high prevalence is linked to a high level of hygiene, i.e.

Erratum to: Glucagon-like peptide-1 analogue, liraglutide, in experimental cerebral malaria: implications for the role of oxidative stress in cerebral malaria.

[This corrects the article DOI: 10.1186/s12936-016-1486-0.].

Oxidative damage and chemokine production dominate days before immune cell infiltration and EAE disease debut.

Background: Multiple sclerosis is widely accepted as an inflammatory disease. However, studies indicate that degenerative processes in the CNS occur prior to inflammation. In the widely used animal model experimental autoimmune encephalomyelitis (EAE), we investigated the significance of degenerative processes from mitochondrial membrane potentials, reactive oxidative species, cell death markers, chemokines, and inflammatory cell types in brain, spinal cord, and optic nerve tissue during the effector phase of the disease, before clinical disease was evident.

Glucagon-like peptide-1 analogue, liraglutide, in experimental cerebral malaria: implications for the role of oxidative stress in cerebral malaria.

Background: Cerebral malaria from Plasmodium falciparum infection is major cause of death in the tropics. The pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ROS/RNS) in the brain is incompletely understood. Insulinotropic glucagon-like peptide-1 (GLP-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ROS/RNS dysfunction.

Systematic review of survival time in experimental mouse stroke with impact on reliability of infarct estimation.

Background: Stroke is the second most common cause of death worldwide. Only one treatment for acute ischemic stroke is currently available, thrombolysis with rt-PA, but it is limited in its use. Many efforts have been invested in order to find additive treatments, without success.

GLP-1 improves neuropathology after murine cold lesion brain trauma.

Objectives: In this study, we address a gap in knowledge regarding the therapeutic potential of acute treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist after severe brain trauma. Moreover, it remains still unknown whether GLP-1 treatment activates the protective, anti-neurodegenerative cAMP response element binding protein (CREB) pathway in the brain in vivo, and whether activation leads to observable increases in protective, anti-neurodegenerative proteins. Finally, we report the first use of a highly sensitive in vivo imaging agent to assess reactive species generation after brain trauma.

Drug-induced hypothermia by 5HT1A agonists provide neuroprotection in experimental stroke: new perspectives for acute patient treatment.

Background: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat stroke model and in man by literature meta-analysis.

Methods: Rats had 60 minutes of middle cerebral artery occlusion (MCAO) and then 7 days of survival.

Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation.

Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI).

Leukocyte infiltration in experimental stroke.

Stroke is one of the leading causes of death worldwide. At present, the only available treatment is thrombolysis, which should be initiated no later than 4.5 hours after onset of symptoms.

In vivo experimental stroke and in vitro organ culture induce similar changes in vasoconstrictor receptors and intracellular calcium handling in rat cerebral arteries.

Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the situation is less clear after focal ischemic stroke. Changes in smooth muscle calcium handling have been implicated in different vascular diseases but have not hitherto been investigated in cerebral arteries after stroke.

Acute but not delayed amphetamine treatment improves behavioral outcome in a rat embolic stroke model.

Objectives: The objective of this study was to examine the effects of d-amphetamine (amph) upon recovery after embolic stroke in rats.

Methods: Ninety-three rats were embolized in the right middle cerebral artery and assigned to: (1) controls; (2) combination (acute amph and later amph-facilitated retraining); (3) late amph (later amph-facilitated retraining alone); and (4) acute amph (acute amph alone). Animals in the combination and in the acute amph groups received a high dose of amph immediately after embolization, while later amph-facilitated retraining in the combination and late amph groups was done by administering a low dose of amph on post-stroke days 2, 5, 8, and 11 followed by retraining in Montoya's Staircase Test.

Cannabinoid treatment renders neurons less vulnerable than oligodendrocytes in Experimental Autoimmune Encephalomyelitis.

Using the rat model Experimental Autoimmune Encephalomyelitis (EAE), we have investigated the cytokinetical and cellular events of axonal degeneration and demyelination following treatment with 5 mg/kg/24h R(+)WIN55,212-2 or 10 mg/kg/24h R(+)WIN55,212-2, which have immunosuppressive effects. EAE was induced using MOG(1-125) in Dark Agouti rats and treatment was initiated at symptom debut and continued until first relapse culminated. The central nervous system (CNS) cell death including caspase and calpain activation, axonal degeneration and demyelination as well as a wide range of immunological parameters were quantified.

Neuroprotection without immunomodulation is not sufficient to reduce first relapse severity in experimental autoimmune encephalomyelitis.

Objectives: Multiple sclerosis can be characterized by a strong neuroinflammatory and progressive neurodegenerative component leading to prolonged disability. The synthetic compound R(+)WIN55,212-2 is reported to be neuroprotective at moderate doses and both neuroprotective and immunomodulatory at high doses, most likely due to differences in receptor affinities. In order to investigate the effects of neuroprotection and immunomodulation in an animal model of multiple sclerosis, we examined the impact of increasing concentrations of R(+)WIN55,212-2 on the inflammatory profile in CNS during first relapse and related this to demyelination, axonal degeneration and relapse severity.

Prolonged drug-induced hypothermia in experimental stroke.

In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia in focal ischemia by pharmacological alteration of the central thermoregulatory set-point.

Anti-apoptotic signaling and failure of apoptosis in the ischemic rat hippocampus.

Several anti-apoptotic proteins are induced in CA1 neurons after transient forebrain ischemia (TFI), but fail to protect the majority of these cells from demise. Correlating cell death morphologies (apoptosis-like and necrosis-like death) with immunohistochemistry (IHC), we investigated whether anti-apoptosis contributes to survival, compromises apoptosis effector functions and/or delays death in CA1 neurons 1-7 days after TFI. As surrogate markers for bioenergetic failure, the IHC of respiratory chain complex (RCC) subunits was investigated.

Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus.

We have investigated the glutamic acid dexcarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control rats (sham-operated and naïve). GAD65 and GAD67 were detected by both in situ hybridization and immunocytochemistry.

Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia.

Cannabinoids have neuroprotective potentials, and the expression of endocannabinoids as well as cannabinoid receptors is induced after cerebral ischemia. They also induce hypothermia by lowering the hypothalamic set point. We have estimated the significance of such hypothermia in ischemic neuroprotection following systemic administration of WIN 55,212-2, a synthetic cannabinoid receptor agonist.

A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption.

Microtubule disruption by colchicine induces apoptosis in selected neuronal populations. However, little is known about the upstream death signalling events mediating the neurotoxicity. We investigated first whether colchicine-induced granule cell apoptosis activates the c-Jun N-terminal kinase (JNK) pathway.