Neurochemistry international
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Review
Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor.
Nerve growth factor (NGF) is critical for the development and maintenance of sympathetic and sensory neurons in the developing nervous system, including nociceptors. In the adult nervous system, NGF is known to produce significant pain signals by binding to the TrkA and p75NTR receptors. Several pathological pain disorders are associated with nerve growth factor dysregulation, including neuropathic pain, osteoarthritic pain, and hyperalgesia. ⋯ However, several chronic pain conditions demonstrate insensitivity to NSAID treatment or the development of detrimental opioid-related side effects, including addiction. As NGF plays an important role in pain generation; antibodies, small molecules and peptides have been designed to antagonize NGF. In this review, we discuss the structural biology of NGF ligand/receptor interaction, and we review current biological and pharmacological strategies to modulate NGF-related pathologies.
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A large body of experimental data and preliminary clinical studies point to the induction of mild hypothermia (32-35 °C) as a valuable approach to control the development of brain edema and intracranial hypertension in acute liver failure (ALF). The ability of hypothermia to affect multiple processes probably explains its efficacy to prevent these cerebral complications. ⋯ Translation of the beneficial effects of therapeutic hypothermia into standard clinical practice, however, needs to be confirmed in adequately designed clinical trials. Such trials will be important to determine the safety of therapeutic hypothermia, to identify which patients might benefit from it, and to provide the optimal guidelines for its use in patients with ALF.
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Stroke-prone spontaneously hypertensive rats (SHRSP/Izm) develop severe hypertension, and more than 95% of them die of cerebral stroke. We showed the vulnerability of neuronal cells of SHRSP/Izm rats. Furthermore, we analyzed the characteristics of SHRSP/Izm astrocytes during a stroke. ⋯ However, attenuated production of lactate and reduced GDNF production in astrocytes may reduce required energy levels and weaken the nutritional status of SHRSP/Ism neuronal cells. We suggest that the attenuation of astrocytes' functions accelerates neuronal cell death during stroke, and may contribute to the development of strokes in SHRSP/Izm. In this review, we summarize the altered properties of SHRSP/Izm astrocytes during a stroke.
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Septic encephalopathy is a frequent complication of the sepsis syndrome, with no therapies available that can prevent the associated neurological dysfunction in humans. It is caused by a number of processes and networks going awry, the exact cellular and molecular mechanisms of which remain an enigma. ⋯ With the observations that brain dysfunction in a sepsis setting can be alleviated by regulation of the cytokines and complement proteins in various species of animals, optimism is building for a possible therapy of sepsis-damaged brain. This article reviewed the advances in the understanding of the underlying mechanisms causing pathology in SE, with an emphasis on the inflammatory and excitatory mediators such as the cytokines, complement proteins and neurotransmitters, investigating their potential as possible therapeutic targets.
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Synaptic plasticity consists in a change in synaptic strength that is believed to be the basis of learning and memory. Synaptic plasticity has been for a very long period of time a hallmark of neurons. ⋯ Because glial cells are all around synapses and release a wide variety of neuroactive molecule during physiological and pathological conditions, glial cells have been reported to modulate synaptic plasticity in many different ways. From change in synaptic coverage, to release of chemokines and cytokines up to dedicated "glio" transmitters release, glia were reported to affect synaptic scaling, homeostatic plasticity, metaplasticity, long-term potentiation and long-term depression.