Astrocytes in functional recovery following central nervous system injuries.

Astrocytes are increasingly recognised as partaking in complex homeostatic mechanisms critical for regulating neuronal plasticity following central nervous system (CNS) insults. Ischaemic stroke and traumatic brain injury are associated with high rates of disability and mortality. Depending on the context and type of injury, reactive astrocytes respond with diverse morphological, proliferative and functional changes collectively known as astrogliosis, which results in both pathogenic and protective effects.

Expression of miR-200c corresponds with increased reactive oxygen species and hypoxia markers after transient focal ischemia in mice.

Embolic stroke results in a necrotic core of cells destined to die, but also a peri-ischemic, watershed penumbral region of potentially salvageable brain tissue. Approaches to effectively differentiate between the ischemic and peri-ischemic zones is critical for novel therapeutic discovery to improve outcomes in survivors of stroke. MicroRNAs are a class of small non-coding RNAs regulating gene translation that have region- and cell-specific expression and responses to ischemia.

Reduction of Inflammation by High-Dose Methylprednisolone Does not Attenuate Oxidative Stress in Children Undergoing Bidirectional Glenn Procedure With or Without Aortic Arch or Pulmonary Arterial Repair.

Objective: Corticosteroids attenuate an inflammatory reaction in pediatric heart surgery. Inflammation is a source of free oxygen radicals. Children with a cyanotic heart defect are prone to increased radical stress during heart surgery.

Stem Cell-Derived Exosomes Protect Astrocyte Cultures From Ischemia and Decrease Injury as Post-stroke Intravenous Therapy.

In the present study, we assessed efficacy of exosomes harvested from human and mouse stem cell cultures in protection of mouse primary astrocyte and neuronal cell cultures following ischemia, and against ischemic stroke . Cell media was collected from primary mouse neural stem cell (NSC) cultures or from human induced pluripotent stem cell-derived cardiomyocyte (iCM) cultures. Exosomes were extracted and purified by polyethylene glycol complexing and centrifugation, and exosome size and concentration were determined with a NanoSite particle analyzer.

Nursing Markedly Protects Postpartum Mice From Stroke: Associated Central and Peripheral Neuroimmune Changes and a Role for Oxytocin.

Recent studies demonstrate significant neuroimmune changes in postpartum females, a period that also carries an increased risk of stroke. Oxytocin, a major hormone upregulated in the brains of nursing mothers, has been shown to both modulate neuroinflammation and protect against stroke. In the present study we assessed whether and how nursing modulates the neuroimmune response and injury after stroke.

Hippocampal sub-regional differences in the microRNA response to forebrain ischemia.

Transient forebrain ischemia, as occurs with cardiac arrest and resuscitation, results in impaired cognitive function secondary to delayed neuronal cell death in hippocampal cornu ammonis-1 (CA1). Comparatively, hippocampal neurons in the adjacent dentate gyrus (DG) survive, suggesting that elucidating the molecular mechanisms underpinning hippocampal sub-regional differences in ischemic tolerance could be central in the development of novel interventions to improve outcome in survivors of forebrain ischemia. MicroRNAs (miRNAs) are non-coding RNAs that modulate the translation of target genes and have been established as an effective therapeutic target for other models of injury.

Pre-treatment with microRNA-181a Antagomir Prevents Loss of Parvalbumin Expression and Preserves Novel Object Recognition Following Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) can result in permanent impairment in memory and learning and may be a precursor to other neurological sequelae. Clinical treatments to ameliorate the effects of mTBI are lacking. Inhibition of microRNA-181a (miR-181a) is protective in several models of cerebral injury, but its role in mTBI has not been investigated.

Pharmacological Preconditioning with Diazoxide in the Experimental Hypothermic Circulatory Arrest Model.

Hypothermic circulatory arrest includes a remarkable risk for neurological injury. Diazoxide, a mitochondrial adenosine triphosphate-dependent potassium ion (K+ATP) channel opener, is known to have cardioprotective effects. We assessed its efficacy in preventing ischemic injury in a clinically relevant animal model.

Remote Ischemic Preconditioning Attenuates Oxidative Stress during Cardiopulmonary Bypass.

Background: Deep hypothermic circulatory arrest (DHCA) is used to overcome the threat of cerebral ischemia during complex surgical operations of the heart and the aortic arch. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurological damage.

Methods: We analyzed blood samples in a consecutive series of 52 piglets that underwent a 60-min period of DHCA with RIPC (the RIPC group) or without (the control group), to reveal whether the protective effect to oxidative stress could be seen by measuring serum 8-hydroxydeoxyguanosine (8-OHdG).

Remote Ischemic Preconditioning Reduces Cerebral Oxidative Stress Following Hypothermic Circulatory Arrest in a Porcine Model.

Remote ischemic precondition has become prominent as one of the most promising methods to mitigate neurological damage following ischemic insult. The purpose of this study was to investigate whether the effects of remote ischemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes in a porcine model. A total of 12 female piglets were randomly assigned to 2 groups.

Remote ischemic preconditioning protects the spinal cord against ischemic insult: An experimental study in a porcine model.

Objective: Surgical repair of thoracoabdominal aneurysm jeopardizes the vascularization of the spinal cord, and therefore, despite improvement in surgical techniques, still carries the risk of paraplegia. This study aimed to demonstrate the possible protective effects of remote ischemic preconditioning (RIPC) on the preservation of spinal cord function after segmental artery (SA) occlusion.

Methods: Twenty piglets were randomized into the RIPC group (n = 10) and the control group (n = 10).

Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model.

Background Aims: Bone marrow mononuclear cells (BM-MNCs) and bone marrow-derived mesenchymal stem stromal cells (BM-MSCs) could have therapeutic potential for numerous conditions, including ischemia-related injury. Cells transplanted intravascularly may become entrapped in the lungs, which potentially decreases their therapeutic effect and increases the risk for embolism.

Methods: Twelve pigs were divided into groups of 3 and received (99m)Tc- hydroxymethyl-propylene-amine-oxime-labeled autologous BM-MNCs or allogeneic BM-MSCs by either intravenous (IV) or intra-arterial (IA) transplantation.

Leg ischaemia before circulatory arrest alters brain leucocyte count and respiratory chain redox state.

Objectives: Remote ischaemic preconditioning and its neuroprotective abilities are currently under investigation and the method has shown significant effects in several small and large animal studies. In our previous studies, leucocyte filtration during cardiopulmonary bypass reduced cerebrocortical adherent leucocyte count and mitigated cerebral damage after hypothermic circulatory arrest (HCA) in piglets. This study aimed to obtain and assess direct visual data of leucocyte behaviour in cerebral vessels after hypothermic circulatory arrest following remote ischaemic preconditioning.

Remote ischemic precondition preserves cerebral oxygen tension during hypothermic circulatory arrest.

Objectives: Remote ischemic preconditioning (RIPC) is a novel and promising method of mitigating neurological injury. In previous animal studies, RIPC has provided substantial neuroprotective effects. We hypothesized that the promising neuroprotective properties were a consequence of a better oxygen consumption profile during hypothermic circulatory arrest (HCA).