Neuroscience
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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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Muscle pain is an important health issue and frequently related to static force exertion. The aim of this study is to evaluate whether peripheral inflammatory mechanisms are involved with static contraction-induced muscle pain in rats. To this end, we developed a model of muscle pain induced by static contraction performed by applying electrical pulses through electrodes inserted into muscle. ⋯ Furthermore, an increased hyperalgesic response was observed when the selective bradykinin B1 agonist des-Arg9-bradykinin was injected into the previously stimulated muscle. Together, these findings demonstrate that static contraction induced mechanical muscle hyperalgesia in gastrocnemius muscle of rats is modulated through peripheral inflammatory mechanisms that are dependent on neutrophil migration, bradykinin, sympathetic amines and prostanoids. Considering the clinical relevance of muscle pain, we propose the present model of static contraction-induced mechanical muscle hyperalgesia as a useful tool for the study of mechanisms underlying static contraction-induced muscle pain.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory. The neurodegeneration induced by AD has been linked to oxidative damage. However, little is known about the involvement of NADPH oxidase 2 (Nox2), a multisubunit enzyme that catalyzes the reduction of oxygen to produce reactive oxygen species, in the pathogenesis of AD. ⋯ STZ treatment increased oxidative damage and pro-inflammatory cytokines' release in Wt mice, which was not observed in gp91phox-/- mice. Nox2 deletion had a positive effect on the IL-10 baseline production, suggesting that this cytokine might contribute to the neuroprotection mechanism against STZ-induced neurodegeneration. In summary, our data suggest that the Nox2-dependent reactive oxygen species (ROS) generation contributes to the STZ-induced AD-like state.
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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.