Neuroscience
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Deep hypothermia therapy (HT) is a standard method for neuroprotection during complex pediatric cardiac surgery involving extracorporeal circulation and deep hypothermic cardiac arrest. The procedure, however, can provoke systemic inflammatory response syndrome (SIRS), one of the most severe side effects associated with pediatric cardiac surgery. To date, the cellular inflammatory mechanisms induced by deep HT remain to be elucidated. ⋯ Moreover, attenuation of the inflammatory response resulted in decreased apoptosis in a direct co-culture of microglia and neurons. HT reduces the inflammatory response in LPS-stimulated BV-2 microglial cells, alluding to a possible mechanism of therapeutic hypothermia-induced neuroprotection. In the future, attenuating the phospho-STAT3 pathway may lead to the development of a neuroprotectant with greater clinical efficacy.
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Recent evidence suggests that ischemia/reperfusion (I/R) in an organ may have distance effect on the brain. In this study, the effects of renal I/R, limb I/R or both together on the structural and function of hippocampus were evaluated and compared. Hence, rats were subjected to 2-h bilateral lower limb ischemia, 45-min bilateral renal ischemia, or combined limb and renal ischemia followed by 1-day reperfusion. ⋯ In the rats with combined limb and renal I/R, the hippocampal neuronal loss and impaired synaptic plasticity were the same as those with limb I/R, but basal synaptic transmission was lowered. In conclusion, the 2-h lower limb ischemia compared to 45-min renal ischemia induced more injurious distant effects on the hippocampus after 1-day reperfusion. The combination of renal and limb I/R did not add or potentiate hippocampal neuronal loss and synaptic plasticity impairment, whereas it decreased the basal synaptic transmission with respect to each one alone.
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Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b+) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b+ RdV neurons is still unclear. ⋯ The majority of Phox2b+ (35/46) and half of the Phox2b- neurons (19/40) did not respond to stimulations of the mesencephalic trigeminal nucleus, the trigeminal tract, and the principal sensory trigeminal nucleus. Biocytin labeling revealed that about half of the Phox2b+ (5/12) and Phox2b- RdV neurons (5/10) send their axons to the trigeminal motor nucleus. These results suggest that Phox2b+ RdV neurons have distinct neurotransmitter phenotypes and firing properties from Phox2b- RdV neurons and might play important roles in feeding-related functions including suckling and possibly mastication.
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Heat Stress (HS) induces diverse pathophysiological changes, which include brain ischemia, oxidative stress and neuronal damage. The present study was undertaken with the objective to ascertain whether neuroinflammation in Hypothalamus (HTH) caused under HS affects monoamine levels and hence, its physiological role in thermoregulation. Rats were exposed to HS in a heat simulation environmental chamber (Ambient temperature, Ta=45±0.5°C and Relative Humidity, RH=30±10%) with real-time measurement of core temperature (Tc) and skin temperature (Ts). ⋯ We found a rise in NE whereas a fall in Serotonin (5-HT) level in HTH at MHS, without perturbing inflammatory mediators. However, rats with SHS exhibited significant elevations in NF-kB, IL-1β, COX2, GFAP and Iba1 protein expression in HTH. In conclusion, the data suggest that SHS induces neuroinflammation in HTH, which is associated with monoamines and Glu imbalances, leading to thermoregulatory disruption.
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The cerebrospinal fluid (CSF)-contacting nucleus is implicated in the descending inhibitory pathway in pain processing, whereas the cellular and molecular mechanisms underpinning CSF-contacting nucleus regulating pain signals remains largely elusive. ATP is evidenced to inhibit pain transmission at supraspinal level by the mediation of the receptor P2X, wherein its subtype P2X3 is identified as the most potent. Our present experiment investigated the functionality of P2X3 receptors in CSF-contacting nucleus in the formalin-evoked inflammatory pain. ⋯ ATP (a P2X3 receptor agonist, 100nmol/5µl) by intracerebroventricular (i.c.v.) administration ameliorated pain behaviors and enhanced c-Fos immunoreactivity in the neurons of the periaqueductal gray (PAG), both of which were discounted by pre-administration of A-317491 (a selective P2X3 receptor antagonist, 25nmol/5µl). After the CSF-contacting nucleus was ablated by cholera toxin subunit B-saporin, ATP failed to induce analgesia, with the c-Fos immunoreactivity in the PAG neurons remaining intact. Our results validated that P2X3 receptors in the CSF-contacting nucleus are pivotal in inflammatory pain processing via the activation of PAG neurons.