Brain research
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To study the effect of simvastatin on neurological functional recovery after traumatic brain injuries (TBI) and the possible molecular mechanisms, we evaluated simvastatin-induced proliferation and differentiation of neural stem cells (NSCs) in vitro and in vivo and possible involvement of Notch-1 signaling in this process. ⋯ Simvastatin treatment enhanced neurological functional recovery after TBI possibly via activation of Notch signaling and increasing neurogenesis in the injured area.
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Parkinson׳s disease (PD) is the most common neurodegenerative disease of the basal ganglia. Earlier reports suggest that the main pathological change in PD is due to apoptosis of dopaminergic neuronal soma in the substantia nigra (SN). The therapies for PD are also largely focused on the prevention of degeneration of the neuronal soma. ⋯ In addition to this, we detect the expression of total and phosphorylated form of Akt, GSK-3β and CRMP-2, as well as the axonal injury marker amyloid precursor protein (APP). From our studies, we observe that axon degeneration is a characteristic feature in the cascade of events that follow when neurons are induced by MPP+. This degeneration process occurs earlier in case of PD and is more severe than the degeneration of the neuronal soma and Akt/ GSK-3β/CRMP-2 pathway is involved in this process.
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Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated anti-migraine efficacy. One remaining question is where do these blockers act? We hypothesized that the trigeminal ganglion could be one possible site. We examined the binding sites of a CGRP receptor antagonist (MK-3207) and related this to the expression of CGRP and its receptor in rhesus trigeminal ganglion. ⋯ This study demonstrates CGRP receptor binding sites and expression of the CGRP receptor in rhesus and rat TG. The expression pattern of PACAP and glutamate suggests a possible interaction between the glutamatergic and CGRP system. In rat the TG is outside the BBB, suggesting that molecules do not need to be CNS-penetrant to block these receptors.
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Apoptosis is critical for the development of cerebral ischemia/reperfusion injury. Thioredoxin-1(Trx-1) protein has been reported to have anti-apoptotic effects in a variety of cell types, and it has been implicated in brain injury after middle cerebral artery occlusion (MCAO). Thus, we studied the effects of Trx1 silencing after MCAO in rats and examined whether inhibition of endogenous Trx1 could increase tissue levels of apoptosis. ⋯ Co-immunoprecipitation assay suggested an interaction between Trx1 and ASK1 in normal rat brains and Trx1 siRNA dissociated ASK1-Trx1 binding complex. Our data suggest that Trx1 siRNA increases apoptotic stress-induced ASK1 activation and this represents further evidence that Trx1 is an endogenous anti-apoptotic molecule that diminishes focal cerebral ischemia/reperfusion injury. Its mechanism of action is likely related to attenuation of the ASK1-JNK/p38 signaling pathway.