Brain research
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Secondary brain insult induced by traumatic brain injury (TBI), including excitotoxicity, oxidative stress, inflammatory response, and neuronal degeneration, is sensitive to therapeutic interventions; therefore, searching for neuroprotective agents represents a promising therapeutic strategy for TBI treatment. Luteolin, a member of the flavonoid family, has recently been proven to modulate autophagy. However, whether it activates autophagy after TBI thereby alleviating the secondary insult is not yet understood. ⋯ In line with these observations, luteolin decreased mRNA and protein expressions of pro-inflammatory factors IL-1b and TNF-a. At last, luteolin reduced neuronal degeneration, and alleviated brain edema and blood-brain barrier (BBB) disruption. In conclusion, these results implied that luteolin protected mice brain from traumatic brain injury by inhibiting inflammatory response, and luteolin-induced autophagy might play a pivotal role in its neuroprotection.
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Estrogen actions on neurons of the principal division of the bed nucleus of the stria terminalis (BNSTpr) are essential for the regulation of female sexual behavior. However, little is known about the effects of estradiol and progesterone (P) on estrogen receptor alpha (ERα) expression in this nucleus. To study this subject, we used stereological methods to estimate the total number of ERα-immunoreactive (ERα-ir) neurons in the BNSTpr of female rats at each stage of the estrous cycle and of ovariectomized rats after administration of estradiol benzoate (EB) and/or P. ⋯ PPT induced no changes in the number of ERα-ir neurons. Contrariwise, DPN induced a decrease in the total number of ERα-ir neurons to values similar to those of EB-treated rats. These results show that P has no effect in the modulation of ERα expression and demonstrate that estradiol regulation of ERα in BNSTpr neurons is mediated by activation of ERβ.
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The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. ⋯ CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug.
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Neurological complications contribute largely to the morbidity and mortality in patients with acute renal failure. In order to study pathophysiological complications of renal failure, a murine model of renal ischemia/reperfusion-induced acute kidney injury (AKI) was generated by 60min bilateral ischemia, and followed by 2h or 24h reperfusion (B-60'IRI). Compared to the sham-operated mice, B-60'IRI mice exhibited a significant inflammatory injury to remote brain. ⋯ The technology of cDNA microarray and quantitated RT-PCR are used to identify hippocampal genes whose expression is altered in response to AKI in B-60' IRI mice. The initiation of transcriptional abnormality was indicated by the finding that B-60' IRI mice exhibited upregulated mRNA levels of genes involved in inflammation, cell signaling, extracellular matrix and cell-cycle regulation and downregulated mRNA levels of genes involved in transporters, G protein-coupled receptor signaling, cell survival and chaperone. Our data suggest that renal IR contributes to a complicated hippocampal gene irregulation in inflammation and physiological homeostasis.
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Neuropathic pain is a form of pathological nociception that occurs in a significant portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. While many peripheral and central mechanisms have been implicated in neuropathic pain, central sensitization of dorsal horn spinothalamic tract (STT) neurons is a major underlying substrate. Furthermore, dysregulation of extracellular glutamate homeostasis and chronic astrocyte activation play important underlying roles in persistent hyperexcitability of these superficial dorsal horn neurons. ⋯ Finally, persistent astrocyte activation and significantly reduced expression of the major CNS glutamate transporter, GLT1, in superficial dorsal horn astrocytes are associated with both excitability changes in STT neurons and the neuropathic pain behavioral phenotype. In conclusion, we have characterized clinically-relevant rodent models of cervical contusion-induced neuropathic pain that result in chronic activation of both STT neurons and astrocytes, as well as compromise in astrocyte glutamate transporter expression. These models can be used as important tools to further study mechanisms underlying neuropathic pain post-SCI and to test potential therapeutic interventions.