Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Dec 2014
ReviewMolecular regulation of cell fate in cerebral ischemia: role of the inflammasome and connected pathways.
Analogous to Toll-like receptors, NOD-like receptors represent a class of pattern recognition receptors, which are cytosolic and constitute part of different inflammasomes. These large protein complexes are activated not only by different pathogens, but also by sterile inflammation or by specific metabolic conditions. ⋯ Increasing data also support an important role in different central nervous diseases such as stroke. Thus, the current knowledge of the functional role of this intracellular 'master switch' of inflammation is discussed with a focus on its role in ischemic stroke, neurodegeneration, and also with regard to the recent data which argues for a relevant role in other organs or biologic systems which influence stroke incidence or prognosis.
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J. Cereb. Blood Flow Metab. · Nov 2014
ReviewLactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations.
Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as 'preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte-neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. ⋯ Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted.
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J. Cereb. Blood Flow Metab. · May 2014
ReviewIn cold blood: intraarteral cold infusions for selective brain cooling in stroke.
Hypothermia is a promising therapeutic option for stroke patients and an established neuroprotective treatment for global cerebral ischemia after cardiac arrest. While whole body cooling is a feasible approach in intubated and sedated patients, its application in awake stroke patients is limited by severe side effects: Strong shivering rewarms the body and potentially worsens ischemic conditions because of increased O2 consumption. Drugs used for shivering control frequently cause sedation that increases the risk of aspiration and pneumonia. ⋯ Preclinical studies and early clinical experience indicate that IACI induce a highly selective brain temperature decrease within minutes and reach targeted hypothermia 10 to 30 times faster than conventional cooling methods. At the same time, body core temperature remains largely unaffected, thus systemic side effects are potentially diminished. This review critically discusses the limitations and side effects of current cooling techniques for neuroprotection from ischemic brain damage and summarizes the available evidence regarding advantages and potential risks of IACI.
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J. Cereb. Blood Flow Metab. · Feb 2014
Review Meta AnalysisCT perfusion and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.
Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem, and can only be confirmed with follow-up imaging. For treatment of DCI a diagnostic tool is needed. We performed a systematic review to evaluate the value of CT perfusion (CTP) in the prediction and diagnosis of DCI. ⋯ Perfusion thresholds reported in studies were comparable, although the corresponding test characteristics were moderate and differed between studies. We conclude that CTP can be used in the diagnosis but not in the prediction of DCI. A need exists to standardize the method for measuring perfusion with CTP after SAH, and optimize and validate perfusion thresholds.
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J. Cereb. Blood Flow Metab. · Sep 2013
ReviewEvidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke.
Although ischemic stroke is a major cause of morbidity and mortality, current therapies benefit only a small proportion of patients. Transplantation of mesenchymal stromal cells (MSC, also known as mesenchymal stem cells or multipotent stromal cells) has attracted attention as a regenerative therapy for numerous diseases, including stroke. Mesenchymal stromal cells may aid in reducing the long-term impact of stroke via multiple mechanisms that include induction of angiogenesis, promotion of neurogenesis, prevention of apoptosis, and immunomodulation. ⋯ An analysis of preclinical studies examining the effects of MSC therapy after ischemic stroke indicates near-universal agreement that MSC have significant favorable effect on stroke recovery, across a range of doses and treatment time windows. These results are interpreted in the context of completed and ongoing human clinical trials, which provide support for MSC as a safe and potentially efficacious therapy for stroke recovery in humans. Finally, we consider principles of brain repair and manufacturing considerations that will be useful for effective translation of MSC from the bench to the bedside for stroke recovery.