Journal of neuroscience research
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Minocycline is a second-generation tetracycline and a potential neuroprotective intervention following brain injury. However, despite the recognized beneficial effects of minocycline in a multitude of adult disease states, the clinical application of minocycline in neonates is contentious. Tetracyclines, as a class, are not usually administered to neonates, but there is compelling evidence that minocycline reduces brain injury after neonatal hypoxic-ischemic brain injury. This Review focuses on the evidence for minocycline use in neonates by considering aspects of pharmacology, drug regimens, functional outcomes, and mechanisms of action.
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Review
Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injury.
The antihypersensitivity actions of gabapentin and pregabalin have been well characterized in a large number of studies, although the underlying mechanisms have yet to be defined. We have been focusing on the supraspinal structure as a possible site for their action and have demonstrated that intracerebroventricular (i.c.v.) administration of gabapentin and pregabalin indeed decreases thermal and mechanical hypersensitivity in a murine chronic pain model involving partial ligation of the sciatic nerve. This novel supraspinally mediated analgesic effect was markedly suppressed by either depletion of central noradrenaline (NA) or blockade of spinal alpha(2)-adrenergic receptors. ⋯ Moreover, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired-pulse ratio, suggesting that gabapentin acts on the presynaptic GABAergic nerve terminals in the LC. Together, the data suggest that gabapentin presynaptically reduces GABAergic synaptic transmission, thereby removing the inhibitory influence on LC neurons only in neuropathic pain states, leading to activation of the descending noradrenergic system.
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It is well known that peripheral sensory stimuli, including pain, trigger a series of neuronal activities along the somatosensory pathways as well as the neuronal network in the high brain structures. These neuronal activities not only produce appropriate physiological responses but also induce long-term plastic changes in some of the central synapses. It is believed that long-term synaptic changes help the brain to process and store new information. ⋯ In the case of permanent injury, however, the brain fails to distinguish the difference between "useful" and painful stimuli. Long-term synaptic changes work against the system and at least in part contribute to chronic pain. In this short article, the possible molecular mechanisms for long-term plasticity within the anterior cingulate cortex (ACC) will be discussed and reviewed, and it is hypothesized that potentiation of excitatory responses within the ACC contributes to chronic pain and pain-related mental disorders.
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Experimental traumatic brain injury (TBI) and spinal cord injury (SCI) result in a rapid and significant necrosis of neuronal tissue at the site of injury. In the ensuing hours and days, secondary injury exacerbates the primary damage, resulting in significant neurologic dysfunction. It is believed that alterations in excitatory amino acids (EAA), increased reactive oxygen species (ROS), and the disruption of Ca(2+) homeostasis are major factors contributing to the ensuing neuropathology. ⋯ The underlying mechanism of neuroprotection afforded by CsA is most likely via interaction with the mPTP because the immunosuppressant FK506, which has no effect on the mPT, was not neuroprotective. When CsA was administrated after experimental SCI at the same dosage and regimen used TBI paradigms, however, it had no beneficial neuroprotective effects. This review takes a comprehensive and critical look at the evidence supporting the role for mPT in central nervous system (CNS) trauma and highlights the differential responses of CNS mitochondria to mPT induction and the implications this has for therapeutically targeting the mPT in TBI and SCI.
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Citicoline, an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in various CNS injury models and neurodegenerative diseases. PtdCho hydrolysis by phospholipase A(2) (PLA(2)) after cerebral ischemia and reperfusion yields arachidonic acid (ArAc) and lyso-PtdCho. ArAc oxidative metabolism results in formation of reactive oxygen species and lipid peroxides. ⋯ S. clinical data suggests that reduction of infarct growth may be a more sensitive measure of the citicoline effect than improvement on the NIH Stroke Scale (NIHSS) by > or =7 points. The citicoline neuroprotective mechanism has not been clearly identified, and its potential in stroke treatment might still be fully recognized in the United States. The clinical efficacy of citicoline should be examined further in light of the recent phase III stroke clinical trials and experimental data for cerebral ischemia.