Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.
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Intracerebral hemorrhage is a devastating disease, and no specific therapy has been proven to reduce mortality in a randomized controlled trial. However, management in a neuroscience intensive care unit does appear to improve outcomes, suggesting that many available therapies do in fact provide benefit. In the acute phase of intracerebral hemorrhage care, strategies aimed at minimizing ongoing bleeding include reversal of anticoagulation and modest blood pressure reduction. ⋯ Selected patients may benefit from hematoma evacuation or external ventricular drainage. Ongoing clinical trials are examining aggressive blood pressure management, hemostatic therapy, platelet transfusion, stereotactic hematoma evacuation, and intraventricular thrombolysis. Finally, preventing recurrence of intracerebral hemorrhage is of pivotal importance, and tight blood pressure management is paramount.
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Cochlear implants provide partial restoration of hearing for profoundly deaf patients by electrically stimulating spiral ganglion neurons (SGNs); however, these neurons gradually degenerate following the onset of deafness. Although the exogenous application of neurotrophins (NTs) can prevent SGN loss, current techniques to administer NTs for long periods of time have limited clinical applicability. We have used encapsulated choroid plexus cells (NTCells; Living Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable manner that can be combined with a cochlear implant. ⋯ Re-sprouting peripheral processes were observed in the scala media and scala tympani, raising the possibility of direct contact between peripheral processes and a cochlear implant electrode array. We conclude that cell-based therapy is clinically viable and effective in promoting SGN survival for extended durations of cochlear implant use. These findings have important implications for the safe delivery of therapeutic drugs to the cochlea.
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Spinal cord injury (SCI) is a serious neurological disorder that debilitates mostly young people. Unfortunately, we still do not have suitable therapeutic agents for treatment of SCI and prevention of its devastating consequences. However, we have gained a good understanding of pathological mechanisms that cause neurodegeneration leading to paralysis or even death following SCI. ⋯ Therefore, inhibition of cysteine proteases is an important goal in prevention of neurodegeneration in SCI. Studies showed that individual inhibitors of cysteine proteases provided significant neuroprotection in animal models of SCI. Recent studies suggest that physiological hormones, such as estrogen and melatonin, can be successfully used for prevention of neurodegeneration and preservation of motor function in acute SCI as well as in chronic SCI in rats.