Functional Improvement after Photothrombotic Stroke in Rats Is Associated with Different Patterns of Dendritic Plasticity after G-CSF Treatment and G-CSF Treatment Combined with Concomitant or Sequential Constraint-Induced Movement Therapy.

We have previously shown that granulocyte-colony stimulating factor (G-CSF) treatment alone, or in combination with constraint movement therapy (CIMT) either sequentially or concomitantly, results in significantly improved sensorimotor recovery after photothrombotic stroke in rats in comparison to untreated control animals. CIMT alone did not result in any significant differences compared to the control group (Diederich et al., Stroke, 2012;43:185-192).

Prevention of an increase in cortical ligand binding to AMPA receptors may represent a novel mechanism of endogenous brain protection by G-CSF after ischemic stroke.

Purpose: Using G-CSF deficient mice we recently demonstrated neuroprotective properties of endogenous G-CSF after ischemic stroke. The present follow-up study was designed to check, whether specific alterations in ligand binding densities of excitatory glutamate or inhibitory GABAA receptors may participate in this effect.

Methods: Three groups of female mice were subjected to 45 minutes of MCAO: wildtype, G-CSF deficient and G-CSF deficient mice substituted with G-CSF.

Effects of levosimendan on hemodynamics, local cerebral blood flow, neuronal injury, and neuroinflammation after asphyctic cardiac arrest in rats.

Objectives: Despite advances in cardiac arrest treatment, high mortality and morbidity rates after successful cardiopulmonary resuscitation are still a major clinical relevant problem. The post cardiac arrest syndrome subsumes myocardial dysfunction, impaired microcirculation, systemic inflammatory response, and neurological impairment. The calcium-sensitizer levosimendan was able to improve myocardial function and initial resuscitation success after experimental cardiac arrest/cardiopulmonary resuscitation.

Distribution of the hematopoietic growth factor G-CSF and its receptor in the adult human brain with specific reference to Alzheimer's disease.

The granulocyte colony-stimulating factor (G-CSF), being a member of the hematopoietic growth factor family, is also critically involved in controlling proliferation and differentiation of neural stem cells. Treatment with G-CSF has been shown to result in substantial neuroprotective and neuroregenerative effects in various experimental models of acute and chronic diseases of the central nervous system. Although G-CSF has been tested in a clinical study for treatment of acute ischemic stroke, there is only fragmentary data on the distribution of this cytokine and its receptor in the human brain.

Postischemic brain infiltration of leukocyte subpopulations differs among murine permanent and transient focal cerebral ischemia models.

Cellular and humoral inflammations play important roles in ischemic brain injury. The effectiveness of immunomodulatory therapies may critically depend on the chosen experimental model. Our purpose was to compare the post-ischemic neuroinflammation among murine permanent and transient middle cerebral artery occlusion (MCAO) models.

Distribution of granulocyte-monocyte colony-stimulating factor and its receptor α-subunit in the adult human brain with specific reference to Alzheimer's disease.

Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a member of the hematopoietic growth factor family, promoting proliferation and differentiation of hematopoietic progenitor cells of the myeloid lineage. In recent years, GM-CSF has also proved to be an important neurotrophic factor in the central nervous system (CNS) via binding to the GM-CSF receptor (GM-CSF R). Furthermore, studies on rodent CNS revealed a wide distribution of both the major binding α-subunit of the GM-CSF R (GM-CSF Rα) and its ligand.

Successful regeneration after experimental stroke by granulocyte-colony stimulating factor is not further enhanced by constraint-induced movement therapy either in concurrent or in sequential combination therapy.

Background And Purpose: Both application of granulocyte-colony stimulating factor (G-CSF) and constraint-induced movement therapy (CIMT) have been shown to improve outcome after experimental stroke. The aim of the present study was to determine whether concurrent or sequential combination of both therapies will further enhance therapeutic benefit and whether specific modifications in the abundance of various neurotransmitter receptors do occur.

Methods: Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to the following treatment groups (n=20 each): (1) ischemic control (saline); (2) CIMT (CIMT between poststroke Days 2 and 11; (3) G-CSF (10 μg/kg G-CSF daily between poststroke Days 2 and 11; (4) combined concurrent group (CIMT plus 10 μg/kg G-CSF daily between poststroke Days 2 and 11; and (5) combined sequential group (CIMT between poststroke Days 2 and 11 and 10 μg/kg G-CSF daily between poststroke Days 12 and 21, respectively).

Dose-dependent influence of sevoflurane anesthesia on neuronal survival and cognitive outcome after transient forebrain ischemia in Sprague-Dawley rats.

Background: Volatile anesthetics reduce postischemic neurohistopathological injury and improve neurological outcome in various animal models. However, the isoflurane concentrations above 1 minimum alveolar concentration (MAC) have been associated with reduced neuronal survival and impaired functional outcome. The aim of this study was to evaluate if 1.

Effects of neural progenitor cells on sensorimotor recovery and endogenous repair mechanisms after photothrombotic stroke.

Background And Purpose: Intravenous neural progenitor cell (NPC) treatment was shown to improve functional recovery after experimental stroke. The underlying mechanisms, however, are not completely understood so far. Here, we investigated the effects of systemic NPC transplantation on endogenous neurogenesis and dendritic plasticity of host neurons.

Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation after stroke.

T lymphocytes are increasingly recognized as key modulators of detrimental inflammatory cascades in acute ischaemic stroke, but the potential of T cell-targeted therapy in brain ischaemia is largely unexplored. Here, we characterize the effect of inhibiting leukocyte very late antigen-4 and endothelial vascular cell adhesion molecule-1-mediated brain invasion-currently the most effective strategy in primary neuroinflammatory brain disease in murine ischaemic stroke models. Very late antigen-4 blockade by monoclonal antibodies improved outcome in models of moderate stroke lesions by inhibiting cerebral leukocyte invasion and neurotoxic cytokine production without increasing the susceptibility to bacterial infections.

Neuroprotective effect of Fn14 deficiency is associated with induction of the granulocyte-colony stimulating factor (G-CSF) pathway in experimental stroke and enhanced by a pathogenic human antiphospholipid antibody.

Using a transgenic mouse model of ischemic stroke we checked for a possible interaction of antiphospholipid antibodies (aPL) which often cause thromboses as well as central nervous system (CNS) involvement under non-thrombotic conditions and the TWEAK/Fn14 pathway known to be adversely involved in inflammatory and ischemic brain disease. After 7 days, infarct volumes were reduced in Fn14 deficient mice and were further decreased by aPL treatment. This was associated with strongest increase of the endogenous neuroprotective G-CSF/G-CSF receptor system.