Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling.

Insufficient remyelination due to impaired oligodendrocyte precursor cell (OPC) differentiation and maturation is strongly associated with irreversible white matter injury (WMI) and neurological deficits. We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2 (LCN2) in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1 (EGR1) as the key signals contributing to LCN2-mediated insufficient OPC remyelination. In LCN-knockdown and OPC EGR1 conditional-knockout mice, we discovered enhanced OPC differentiation in developing and injured white matter (WM); consistent with this, the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical, acute WMI due to subarachnoid hemorrhage and typical, chronic WMI due to multiple sclerosis.

The projections from the anterior cingulate cortex to the nucleus accumbens and ventral tegmental area contribute to neuropathic pain-evoked aversion in rats.

Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve.

Nexilin Regulates Oligodendrocyte Progenitor Cell Migration and Remyelination and Is Negatively Regulated by Protease-Activated Receptor 1/Ras-Proximate-1 Signaling Following Subarachnoid Hemorrhage.

Progressive white matter (WM) impairments caused by subarachnoid hemorrhage (SAH) contribute to cognitive deficits and poor clinical prognoses; however, their pathogenetic mechanisms are poorly understood. We investigated the role of nexilin and oligodendrocyte progenitor cell (OPC)-mediated repair in a mouse model of experimental SAH generated left endovascular perforation. Nexilin expression was enhanced by the elevated migration of OPCs after SAH.

Aspirin increases ferroportin 1 expression by inhibiting hepcidin via the JAK/STAT3 pathway in interleukin 6-treated PC-12 cells.

To understand the potential mechanisms involved in the beneficial effects of aspirin (ASA) in mood disorders, Alzheimer's (AD) and Parkinson's disease (PD), we investigated the effects of ASA on the expression of iron transport proteins transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), and iron storage protein ferritin light chain (Ft-L) in interleukin-6 (IL-6)-treated PC-12 cells. We demonstrated that IL-6 alone could induce a severe decline in Fpn1 expression and cell viability, and an increase in Ft-L protein, while ASA could markedly diminish the effects of IL-6 on these parameters. We also found that IL-6 significantly increased hepcidin expression and janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, while ASA also observably suppressed these IL-6-induced effects.

Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats.

: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. : This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia.

Inhibition of Metabotropic Glutamate Receptor Subtype 1 Alters the Excitability of the Commissural Pyramidal Neuron in the Rat Anterior Cingulate Cortex after Chronic Constriction Injury to the Sciatic Nerve.

Background: Inhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied.

Methods: Retrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve.

Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats.

Angiographic vasospasm, especially in the early phases (<72h) of subarachnoid hemorrhage (SAH), is one of the major complications after an aneurysm rupture and is often the cause of delayed neurological deterioration. Scutellarin (SCU), a flavonoid extracted from the traditional Chinese herb Erigeron breviscapus, has been widely accepted as an antioxidant, but the effect of SCU on vasospasm after SAH remains elusive. Endovascular perforation was conducted to induce SAH in Sprague-Dawley rats.

Pericyte: Potential Target for Hemorrhagic Stroke Prevention and Treatment.

Background: Despite long-standing and worldwide efforts, hemorrhagic stroke remains a critical clinical syndrome that exerts a heavy toll on affected individuals and their families due to the lack of preventive and therapeutic targets.

Objective: To clarify the pathogenesis of hemorrhagic stroke and to identify novel therapeutic targets.

Method: Targeting pericytes, the typical mural cells of microvessels, could serve as a way to modulate microvascular permeability, development, and maturation by regulating endothelial cell functions and modulating tissue fibrosis and inflammatory responses.

Hemoglobin induced NO/cGMP suppression Deteriorate Microcirculation via Pericyte Phenotype Transformation after Subarachnoid Hemorrhage in Rats.

Subarachnoid hemorrhage (SAH) usually results from ruptured aneurysm, but how leaked hemoglobin regulates the microcirculation in the pathophysiology of early brain injury after SAH is still unclear. In the present study, we sought to investigate the role and possible mechanism of hemoglobin induced pericyte phenotype transformation in the regulation of microcirculation after SAH. Endovascular perforation SAH rat model, brain slices and cultured pericytes were used, and intervened with endothelial nitric oxide synthase (eNOS) antagonist L-NNA and its agonist scutellarin, hemoglobin, DETA/NO (nitric oxide(NO) donor), PITO (NO scavenger), 8-Br-cGMP (cGMP analog).

Activation of mGluR1 contributes to neuronal hyperexcitability in the rat anterior cingulate cortex via inhibition of HCN channels.

Neuronal hyperexcitability in the anterior cingulate cortex (ACC) is considered as one of the most important pathological changes responsible for the chronification of neuropathic pain. However, the underlying mechanisms remain elusive. In the present study, we investigated the possible mechanisms using a rat model of chronic constriction injury (CCI) to the sciatic nerve.

Alteration in rectification of potassium channels in perinatal hypoxia ischemia brain damage.

Oligodendrocyte progenitor cells (OPCs) are susceptible to perinatal hypoxia ischemia brain damage (HIBD), which results in infant cerebral palsy due to the effects on myelination. The origin of OPC vulnerability in HIBD, however, remains controversial. In this study, we defined the HIBD punctate lesions by MRI diffuse excessive high signal intensity (DEHSI) in postnatal 7-day-old rats.

Activation of cyclic AMP/PKA pathway inhibits bladder cancer cell invasion by targeting MAP4-dependent microtubule dynamics.

Objective: With the notorious reputation of the vicious invasion, the bladder cancer is the most common malignant tumor of the urinary system. Inhibiting invasion through microtubule dynamics interruption has emerged as an important treatment of bladder cancer. Here we investigated the role of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway in human bladder cancer cells invasion.

Inhibition of HCN channels within the periaqueductal gray attenuates neuropathic pain in rats.

Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels play important roles in neuropathic pain by regulating neuronal excitability. However, the participation of HCN channels in the ventral-lateral periaqueductal gray (vlPAG) during neuropathic pain states has not been clarified. To investigate the role of vlPAG HCN channels in neuropathic pain, the authors developed a chronic constriction injury (CCI) model.

The role of HCN channels within the periaqueductal gray in neuropathic pain.

Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a key role in neuropathic pain by regulating neuronal excitability. HCN channels are expressed in the ventral-lateral periaqueductal gray (vlPAG), a region that is important for pain modulation. However, the role of vlPAG HCN channels in neuropathic pain remains poorly understood.

Expression of P2X5 receptors in the rat, cat, mouse and guinea pig dorsal root ganglion.

P2X receptors are ATP-gated cationic channels composed of seven cloned subunits (P2X(1 -7)). P2X(3) homomultimer and P2X(2/3) heteromultimer receptors expressed by primary afferent dorsal root ganglion (DRG) neurons are involved in pain processing. The aim of the study was to investigate the expression of the P2X(5) receptor subunit in DRG in different species including mouse, rat, cat and guinea pig.

Functional response of hippocampal CA1 pyramidal cells to neonatal hypoxic-ischemic brain damage.

Perinatal hypoxic-ischemic (H-I) is a major cause of brain injury in the newborn. The hippocampus is more sensitive to H-I injury than the other brain regions. It is believed that H-I brain damage causes a loss of neurons in the central nervous system.

Effect of hypobaric hypoxia on the P2X receptors of pyramidal cells in the immature rat hippocampus CA1 sub-field.

Primary Objective: This study was designed to evaluate the effect of hypobaric hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus CA1 pyramidal cells.

Research Design: The functional changes of P2X receptors were investigated through the cell HH model and the expressional alterations of P2X receptors were observed through the animal HH model.

Methods And Procedure: P2X receptors mediated currents were recorded from the freshly dissociated CA1 pyramidal cells of 7-day-old SD rats by whole cell patch clamp recording.

Spinal P2X(7) receptor mediates microglia activation-induced neuropathic pain in the sciatic nerve injury rat model.

P2X(7) receptor is an important member of ATP-sensitive ionotropic P2X receptors family, which includes seven receptor subtypes (P2X(1)-P2X(7)). Recent evidence indicates that P2X(7)R participates in the onset and persistence of neuropathic pain. In tetanic stimulation of the sciatic nerve model, P2X(7)R was involved in the activation of microglia, but whether this happens in other neuropathic pain models remains unclear.

Prevention of extracellular ADP-induced ATP accumulation of the cultured rat spinal astrocytes via P2Y(1)-mediated inhibition of AMPK.

P2Y(1) is probably an important subtype of purinergic receptors (P2Rs) in modulation of the astrocyte activation in spinal cord. The aim of this study was to observe the effect of P2Y(1) receptor on the abnormal energy metabolism of the cultured rat spinal astrocyte induced by extracellular adenosine diphosphate (ADP). The results showed that adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) in the astrocytes were up-regulated in the presence of ADP, which could be enhanced by MRS2179, a specific antagonist for P2Y(1) receptor.

Effect of lappaconitine on neuropathic pain mediated by P2X3 receptor in rat dorsal root ganglion.

ATP facilitates initiation and transmission of the neuropathic pain at the dorsal root ganglion (DRG) level via the P2X receptors, especially the subtype P2X(3). Lappaconitine (LA) is an active principle isolated from Chinese herbal medicine and possesses analgesic effect. The aim of this study was to investigate the effect of LA on chronic constriction injury (CCI)-induced neuropathic pain mediated by P2X(3) receptor in the DRG neurons.

Facilitation of Ih channels by P2Y1 receptors activation in Mesencephalic trigeminal neurons.

P2Y(1) receptors, a subset of G-protein coupled receptors, have been shown to participate in sensory transduction in the periphery nervous system. However, little is known about their sensory function in the central nervous system. Here, by using immunohistochemistry, we showed that P2Y(1) receptors are predominantly localized in the somata of Mesencephalic trigeminal neurons (Mes V neurons), the primary sensory neurons in brainstem.

Role of midbrain periaqueductal gray P2X3 receptors in electroacupuncture-mediated endogenous pain modulatory systems.

Extracellular ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors and the P2X3 subtype is an important candidate for this effect. Electroacupuncture (EA) has been clinically utilized to manage chronic pain. In this study, with neuropathic pain model of Sprague-Dawley (SD) rats, the P2X3 receptor protein level and expression location in the midbrain periaqueductal gray (PAG), a crucial site in endogenous pain modulatory system, were evaluated by Western blotting and immunohistochemistry.

Inhibition of ATP-induced Ca2+ influx by corticosterone in dorsal root ganglion neurons.

In addition to the classic genomic effects, it is well known that glucocorticoids also have rapid, nongenomic effects on neurons. In the present study, the effect of corticosterone (CORT) on ATP-induced Ca(2+) mobilization in cultured dorsal root ganglion (DRG) neurons were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator that could monitor real-time alterations of intracellular calcium concentration ([Ca(2+)]i). ATP, an algesic agent, caused [Ca(2+)]i increase in DRG neurons by activation of P2X receptor.