Neuroscience
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Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic factor. Recently, this factor has been shown to exhibit neuroprotective effects on many CNS injuries. Spinal cord ischemic injury that frequently results in paraplegia is a major cause of morbidity after thoracic aorta operations. ⋯ In addition, G-CSF inhibited the ischemia-induced activation of p38 in the astrocytes. Furthermore, we concluded that i.t. G-CSF produced a significant increase in phospho-Akt and phospho-ERK in the motor neurons and exhibited beneficial effects on the spinal cord ischemia-induced neurological defects.
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The concentration of intracellular Ca(2+) ([Ca(2+)](i)) influences neuronal properties ranging from excitability to neurotransmitter release. Persistent inflammation is associated with changes in the properties of primary afferent neurons ranging from excitability to transmitter release. The purpose of the present study was to determine whether previously described inflammation-induced changes in excitability and transmitter release are associated with changes in the regulation of [Ca(2+)](i). ⋯ Furthermore, there were differences among subpopulations of DRG neurons with respect to changes in magnitude and/or decay of the evoked transient such that the increase in magnitude was larger in small- and medium-diameter neurons than in large diameter neurons while the decrease in the decay was greater in CAP responsive, IB4 positive, small- and medium-diameter neurons than in CAP unresponsive, IB4 negative and/or large-diameter neurons. These changes in the regulation of [Ca(2+)](i) were not due to inflammation-induced changes in passive or active electrophysiological properties. Importantly, an inflammation-induced increase in evoked Ca(2+) transients in putative nociceptive afferents may contribute to the pain and hyperalgesia associated with persistent inflammation via facilitation of transmitter release from these afferents.
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A wide variety of human and animal experiments suggest that the anterior cingulate cortex (ACC) is one of the key brain substrates subserving higher order processing of noxious information. However, no sufficient data are now available regarding the mediation by ACC of different levels of pain processing as well as its potential descending modulation of spinal nociception. Using the well-developed rat bee venom (BV) model, the present study evaluated the effect of lesions of bilateral ACC on two levels of spontaneous nociceptive behaviors (spinally-processed persistent paw flinching reflex and supraspinally-processed paw lifting/licking) and heat or mechanical hypersensitivity under the inflammatory pain state. ⋯ Motor coordination, as measured by Rota-Rod treadmill test, was not impaired by bilateral ACC lesions. These results implicate that the ACC area of the brain plays differential roles in the mediation of different levels of spontaneous pain-related behaviors. The present study also provides additional evidence for the ACC-mediated descending facilitation of primary hyperalgesia (pain hypersensitivity) identified in the injured area under inflammatory pain state.
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Following immature excitotoxic brain damage, distinct patterns of caspase activation have been described in neurons and glial cells. Neuronal cells show activation of the mitochondrial apoptosis pathway, caspase-3 cleavage and apoptotic cell death, while reactive astrocytes show caspase-3 cleavage that is not always correlated with enzymatic protease activity and does not generally terminate in cell death. Accordingly, the aim of the present study was to evaluate the astrocytic colocalization of cleaved caspase-3 and several anti-apoptotic proteins of the inhibitor of apoptosis proteins family (IAPs), such as survivin and cellular inhibitor of apoptosis-2 (cIAP-2), and the heat shock proteins (HSPs) family, Hsp25/27 and Hsc70/Hsp70, which can all prevent caspases from cleaving their substrates. ⋯ Survivin is primarily located in the nucleus, like cleaved caspase-3; while Hsp25/27 is cytoplasmic but very frequently found in cells showing nuclear caspase-3. cIAP-2 was mostly found in damaged neurons but also in some glial scar reactive astrocytes and showed fewer correlation with caspase-3. Hsc70/Hsp70 was only expressed in injured neurons and did not correlate with caspase-3. Thus, we conclude that primarily survivin and Hsp25/27 may participate in the inhibition of cleaved caspase-3 in reactive astrocytes and may be involved in protecting astrocytes after injury.
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Onset of auditory brainstem responses in chickens takes place at about embryonic day 11/12 (E11/12). We investigated early development of neuronal properties of chicken nucleus laminaris neurons, the third-order auditory neurons critically involved in sound localization. Whole-cell patch recordings were performed in brainstem slices obtained at E10, E11, E12, E14, E16, and E18. ⋯ Excitatory postsynaptic potentials (EPSPs) were first recorded at E10, prior to and independent of the cochlear afferent inputs from the auditory nerve to the cochlear nucleus. EPSPs became markedly briefer in duration during the period studied. We conclude that the basic features of the key neuronal properties of NL neurons are well constructed during early development from E10 to E18.