Longitudinal Assessments of Normal and Perilesional Tissues in Focal Brain Ischemia and Partial Optic Nerve Injury with Manganese-enhanced MRI.

Although manganese (Mn) can enhance brain tissues for improving magnetic resonance imaging (MRI) assessments, the underlying neural mechanisms of Mn detection remain unclear. In this study, we used Mn-enhanced MRI to test the hypothesis that different Mn entry routes and spatiotemporal Mn distributions can reflect different mechanisms of neural circuitry and neurodegeneration in normal and injured brains. Upon systemic administration, exogenous Mn exhibited varying transport rates and continuous redistribution across healthy rodent brain nuclei over a 2-week timeframe, whereas in rodents following photothrombotic cortical injury, transient middle cerebral artery occlusion, or neonatal hypoxic-ischemic brain injury, Mn preferentially accumulated in perilesional tissues expressing gliosis or oxidative stress within days.

Selective astrocytic endothelin-1 overexpression contributes to dementia associated with ischemic stroke by exaggerating astrocyte-derived amyloid secretion.

Endothelin-1 (ET-1) is synthesized by endothelial cells and astrocytes in stroke and in brains of Alzheimer's disease patients. Our transgenic mice with ET-1 overexpression in the endothelial cells (TET-1) showed more severe blood-brain barrier (BBB) breakdown, neuronal apoptosis, and glial reactivity after 2-hour transient middle cerebral artery occlusion (tMCAO) with 22-hour reperfusion and more severe cognitive deficits after 30 minutes tMCAO with 5 months reperfusion. However, the role of astrocytic ET-1 in contributing to poststroke cognitive deficits after tMCAO is largely unknown.

Targeted Overexpression of Astrocytic Endothelin-1 Attenuates Neuropathic Pain by Upregulating Spinal Excitatory Amino Acid Transporter-2.

We previously demonstrated that endogenous endothelin-1 (ET-1) inhibits pathological pain in a transgenic mouse model with astrocyte-specific ET-1 overexpression (GET-1 mice); however, the underlying mechanism is unclear. ET-1 regulates excitatory amino acid transporter-2 (EAAT-2), a predominant subtype of glutamate transporters that plays critical role in pain modulation in spinal astrocytes. We hypothesized that astrocytic ET-1 overexpression alleviates neuropathic pain through modulating EAAT-2.

Over-expression of astrocytic ET-1 attenuates neuropathic pain by inhibition of ERK1/2 and Akt(s) via activation of ETA receptor.

A differential role of endothelin-1 (ET-1) in pain processing has recently been suggested. However, the function of central ET-1 in neuropathic pain (NP) has not been fully elucidated to date. We report here the action of endogenous central ET-1 in sciatic nerve ligation-induced NP (SNL-NP) in a transgenic animal model that over-expresses ET-1 in the astrocytes (GET-1 mice).

Effects of repeated central administration of endothelin type A receptor antagonist on the development of neuropathic pain in rats.

Endothelin-1 (ET-1) predominates in the endothelin family effectively in vascular tone control, mitogenesis, and neuromodulation. Its receptors are widespread in the central nervous system (CNS) associated with endogenous pain control, suggesting an important role of ET-1 in central pain processing. This study aimed to evaluate the effect of central ET-1 on the development of neuropathic pain behaviour by repeated intrathecal administration of endothelin type A receptor (ETAR) antagonist (BQ-123) in a sciatic nerve ligation (SNL) animal model.

Modulation of endoplasmic reticulum chaperone GRP78 by high glucose in hippocampus of streptozotocin-induced diabetic mice and C6 astrocytic cells.

Diabetes mellitus is known to increase the risk of neurodegeneration, and both diseases are reported to be linked to dysfunction of endoplasmic reticulum (ER). Astrocytes are important in the defense mechanism of central nervous system (CNS), with great ability of tolerating accumulation of toxic substances and sensitivity in Ca(2+) homeostasis which are two key functions of ER. Here, we investigated the modulation of the glucose-regulated protein 78 (GRP78) in streptozotocin (STZ)-induced diabetic mice and C6 cells cultured in high glucose condition.

Over-expression of endothelin-1 in astrocytes, but not endothelial cells, ameliorates inflammatory pain response after formalin injection.

Aims: Endothelin-1 (ET-1) has been suggested to be involved in different types of pain due to its neuromodulatory nature. However, its role in inflammatory pain processing, specifically the origin-specific effect, has not yet been clearly defined. Therefore, the aim of this study is to determine the role of cell-type specific ET-1 induction in the modulation of inflammatory pain processing.

Early detection of neurodegeneration in brain ischemia by manganese-enhanced MRI.

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect neurodegenerative changes in two models of brain ischemia, photothrombotic cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in rodents. After systemic Mn(2+) injection to both ischemic models, a close pattern of T1-weighted hyperintensity was observed throughout different brain regions in comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby conventional MRI could hardly detect such. In addition, the infarct volumes in the posterior parts of the brain had significantly reduced after Mn(2+) injection to the MCAO model.

Deletion of aldose reductase leads to protection against cerebral ischemic injury.

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury.

Type II topoisomerase activities in both the G1 and G2/M phases of the dinoflagellate cell cycle.

Dinoflagellate genomes are large (up to 200 pg) and are encoded in histoneless chromosomes that are quasi-permanently condensed. This unique combination of chromosomal characteristics presents additional topological and cell cycle control problems for a eukaryotic cell, potentially exhibiting novel regulatory requirements of topoisomerase II. The heterotrophic dinoflagellate Crypthecodinium cohnii was used in this study.

Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet.

Stroke patients have increased levels of endothelin-1 (ET-1), a strong vasoconstrictor, in their plasma or cerebrospinal fluid. Previously, we showed high level of ET-1 mRNA expression in astrocytes after hypoxia/ischemia. It is unclear whether the contribution of ET-1 induction in astrocytes is protective or destructive in cerebral ischemia.