Amelioration of Behavioral Impairments and Neuropathology by Antiepileptic Drug Topiramate in a Transgenic Alzheimer's Disease Model Mice, APP/PS1.

Alzheimer's disease (AD) is a neurodegenerative disease that is the main cause of dementia in the elderly. The aggregation of β-amyloid peptides is one of the characterizing pathological changes of AD. Topiramate is an antiepileptic drug, which in addition, is used in the treatment of many neuropsychiatric disorders.

Protective Effects of Forskolin on Behavioral Deficits and Neuropathological Changes in a Mouse Model of Cerebral Amyloidosis.

The production of amyloid-β peptides in the brains of patients with Alzheimer disease (AD) may contribute to memory loss and impairments in social behavior. Here, an efficient adenylate cyclase activator, forskolin, was orally administered by gavage (100 mg/kg body weight) to 5-month-old transgenic APP/PS1 mice, which serve as an animal model of cerebral amyloidosis. Analyses of nest construction, sociability, and immunohistochemical features were used to determine the effects of forskolin treatment.

Systemic administration of valproic acid stimulates overexpression of microtubule-associated protein 2 in the spinal cord injury model to promote neurite outgrowth.

Objectives: Growing body of evidence suggests that neurite outgrowth is a key determinant in the re-networking of damaged neuronal circuits as well as synaptogenesis. The essential molecule in this interesting process is microtubule-associated protein 2 (MAP2) studies demonstrated that inhibition of MAP2 by antisense Oligonucleotide hinders neurite outgrowth.

Methods: In the current study, we evaluated the effects of valproic acid (VPA), a histone deacetylase inhibitor on the expression of MAP2 in the rat spinal cord injury model by real time RT-PCR and immunoreactivity assays.

Icariin ameliorates neuropathological changes, TGF-β1 accumulation and behavioral deficits in a mouse model of cerebral amyloidosis.

Icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, exhibits multiple biological properties, including anti-inflammatory, neuroregulatory and neuroprotective activities. Therefore, Icariin might be applied in treatment of neurodegenerative disorders, including Alzheimer's disease (AD), which is neuropathologically characterized by β-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Potential therapeutic effects of Icariin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mouse.

Key network approach reveals new insight into Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder without curative treatment. Extensive data on pathological molecular processes have been accumulated over the last years. These data combined allows a systems biology approach to identify key regulatory elements of AD and to establish a model descriptive of the disease process which can be used for the development of therapeutic agents.

Accumulation of connective tissue growth factor+ cells during the early phase of rat traumatic brain injury.

Background: Glial scar formation is a common histopathological feature of traumatic brain injury (TBI). Astrogliosis and expression of transforming growth factor beta (TGF-β) are key components of scar formation and blood-brain barrier modulation. Connective tissue growth factor (CTGF) is considered a cytokine mediating the effects of TGF-β.

Accumulation of fascin+ cells during experimental autoimmune neuritis.

Background: Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.

Methods: Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin + cells in sciatic nerves of EAN rats.

Entada africana fraction CH₂Cl₂/MEOH 5% inhibits inducible nitric oxide synthase and pro-inflammatory cytokines gene expression induced by lipopolysaccharide in microglia.

Background: Inflammatory response in the CNS mediated by microglia cells play an important role in host defense and is implicated in the pathology of neurodegenerative diseases. We investigated the capacity of Entada africana to protect microglia from inflammatory insults by exploring the effect of the CH₂Cl₂/MEOH 5% fraction (Ea5) on pro-inflammatory cytokines mRNA expression. Finally, we studied the effect of Ea5 on the inhibition of p38 MAPK Kinase.

Oridonin ameliorates neuropathological changes and behavioural deficits in a mouse model of cerebral amyloidosis.

Alzheimer's disease (AD) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by β-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti-inflammatory and neuroregulatory activities.

A fraction of stem bark extract of Entada africana suppresses lipopolysaccharide-induced inflammation in RAW 264.7 cells.

Ethnopharmacological Relevance: Entada africana is a plant used in African traditional medicine for the treatment of stomachache, fever, liver related diseases, wound healing, cataract and dysentery.

Aims Of The Study: This study aimed at evaluating the anti-inflammatory activity of fractions of the stem bark extract of the plant using lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages model.

Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN), an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system, is characterized by self-limitation. Here we investigated the regulation and contribution of erythropoietin (EPO) in EAN self-limitation. In EAN sciatic nerves, hypoxia, and protein and mRNA levels of hypoxia-inducible factor 1α (HIF-1α), HIF-2α, EPO and EPO receptor (EPOR) were induced in parallel at disease peak phase but reduced at recovery periods.

Lesional accumulation of heme oxygenase-1+ microglia/macrophages in rat traumatic brain injury.

Heme oxygenase-1 (HO-1) is an inducible rate-limiting enzyme for heme degradation. Here, we studied the HO-1 expression in an open-skull weight-drop-induced traumatic brain injury, with a focus on the early phase, most amenable to therapy. In normal rat brains of our study, HO-1 cells were rarely observed.

Oral administration of histone deacetylase inhibitor MS-275 ameliorates neuroinflammation and cerebral amyloidosis and improves behavior in a mouse model.

Alzheimer disease is the most common neurodegenerative disease and the major cause of dementia. In addition to β-amyloid aggregation and hyperphosphorylated tau, neuroinflammation also plays important roles in the pathophysiology of this multifactorial disorder. Histone deacetylase catalyzes deacetylation of histones and has important roles in the regulation of gene expression.

Nanosilver: application and novel aspects of toxicology.

Nanomaterials are a challenge to toxicology. The high diversity of novel materials and products will require extensive expertize for evaluation and regulatory efforts. Nanomaterials are of substantial scientific and economic potential.

Lesional infiltration of receptor activator of nuclear factor-κB ligand⁺ cells in experimental autoimmune neuritis rats.

Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune demyelinating inflammatory disease of the peripheral nervous system. Receptor activator of NF-κB ligand (RANKL), a member of the tumor necrosis factor family, regulates proliferation of mature T cells. Here, we have studied the expression of RANKL in sciatic nerves of EAN rats.

Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science.

Background: The primary phase of traumatic spinal cord injury (SCI) starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. Valproic acid (VPA) is a histone deacetylase inhibitor. Acetylation of histones is critical to cellular inflammatory and repair processes.

Antimicrobial peptides in the brain: neuropeptides and amyloid.

Antimicrobial peptides (AMPs) are ancient defense molecules of the innate immune system. Similarly, neuropeptides are ancient signaling molecules. Similarities in size, cationic charge or amphipatic design between some neuropeptides and AMPs suggest that they might serve an additional function in antimicrobial immunity.

Lesional accumulation of CD163+ macrophages/microglia in rat traumatic brain injury.

A robust neuroinflammation, contributing to the development of secondary injury, is a common histopathological feature of traumatic brain injury (TBI). Characterization of leukocytic subpopulations contributing to the early infiltration of the damaged tissue might aid in further understanding of lesion development. Reactive macrophages/microglia can exert protective or damaging effects in TBI.

The profile of β-amyloid precursor protein expression of rats induced by aluminum.

The environmental agent aluminum has been extensively investigated for a potential relationship with amyloid precursor protein (APP) expression. Despite many investigations, there is at present no definite proof from which to draw a conclusion. Since APP is an integral membrane protein expressed in different tissues and capable of fluxes across the blood-brain barrier (BBB), which may ultimately affect APP level in brain, it is necessary to assess the expression profile among vital body organs.

Immunolocalization of Toll-like receptors 2 and 4 as well as their endogenous ligand, heat shock protein 70, in rat traumatic brain injury.

Objective: Toll-like receptors (TLRs) are essential to the innate immune system for recognizing not only microbial pathogens but also endogenous ligands from injured cells, suggesting that TLRs are a sensitive detection system to tissue injury and play roles in initiating tissue degeneration/regeneration. In this study, the effects of traumatic brain injury (TBI) on lesional expression of TLR2, TLR4, their most common adaptor molecule myeloid differentiation factor 88 (MyD88) and their endogenous ligand, heat shock protein 70 (HSP70), were investigated.

Methods: Rat TBI was induced using an open-skull weight-drop model.

Distinct expression of Tim-3 during different stages of rat experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Tim-3 had been identified as a Th1-specific marker negatively regulating autoimmunity or inflammatory diseases. Here we have studied by immunohistochemistry the spatiotemporal accumulation of Tim-3(+) cells in sciatic nerves of EAN rats, particularly focusing on its association with alternatively activated macrophages.

Parenchymal accumulation of CD163+ macrophages/microglia in multiple sclerosis brains.

Reactive macrophages/microglia exert both protective or damaging effects in multiple sclerosis (MS), which contribute to the relapsing-remitting nature of MS. CD163 is considered a marker of M2 (alternatively activated) macrophages. In the MS brain, CD163(+) perivascular macrophages express molecules for antigen recognition and presentation.

Doxycycline attenuates peripheral inflammation in rat experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system and widely-used animal model of human inflammatory demyelinating polyradiculoneuropathies. Doxycycline is a well-known antibiotic and has been reported to have neuroprotective and anti-inflammatory effects. Here we investigated the effects of doxycycline on rat EAN.

HDAC inhibitor MS-275 attenuates the inflammatory reaction in rat experimental autoimmune prostatitis.

Background: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of male sex accessory glands and is characterized by a cellular and humoral prostate-specific autoimmune response. EAP shares important clinical and immunological features with human chronic prostatitis and chronic pelvic pain syndrome. MS-275, a potent histone deacetylase inhibitor, has promising anti-inflammatory activities and might be a new agent in the therapy of prostate inflammation.

Perfluorooctane sulfonate induces apoptosis in N9 microglial cell line.

Perfluorooctane sulfonate (PFOS) is an environmental persistent acid found at low levels in human, wildlife, and environmental media samples. To study the apoptosis effects of PFOS on microglia, murine N9 cell line was used as a model in current research. The results showed that PFOS could reduce the cell viability significantly, and the cellular apoptosis induced by PFOS was closely accompanied with dissipation of mitochondria membrane potential, upregulation messenger RNAs (mRNAs) of p53, Bax, caspase 9, and caspase 3, and decreased expression of Bcl-2 mRNA.