Status epilepticus induces vasogenic edema via tumor necrosis factor-α/ endothelin-1-mediated two different pathways.

Status epilepticus (SE) induces vasogenic edema in the piriform cortex with disruptions of the blood-brain barrier (BBB). However, the mechanisms of vasogenic edema formation following SE are still unknown. Here we investigated the endothelin B (ETB) receptor-mediated pathway of SE-induced vasogenic edema.

The effect of P2X7 receptor activation on nuclear factor-κB phosphorylation induced by status epilepticus in the rat hippocampus.

Nuclear factor-kappa B (NFκB) signal is essential for neuronal survival and its activation may protect neuron against various stimuli. Since purinergic signals activate NFκB through the P2X7 receptor, we investigated the distinct pattern of NF-κB phosphorylation in neurons by P2X7 receptor activation following status epilepticus (SE) in an effort to understand the role of P2X7 receptor in epileptogenic insult. In non-SE animals, 2'(3')-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP, a P2X7R agonist) treatment increased only p52-Ser869 NF-κB phosphorylation in neuron.

Differential nuclear factor-kappa B phosphorylation induced by lipopolysaccharide in the hippocampus of P2X7 receptor knockout mouse.

Objective: Lipopolysaccharide (LPS) stimulates the innate immune response in the brain through nuclear factor-kappaB (NF-kappaB) signaling. Since purinergic signals activate NF-kappaB through the P2X7 receptor (P2X7R), we investigated the roles of P2X7R in neuronal NF-kappaB phosphorylation in the mouse hippocampus under basal conditions and P2X7R deletion following LPS treatment in vivo.

Methods: We performed immunohistochemical studies for neuronal NF-kappaB phosphorylation in the hippocampi of wild type (WT) and P2X7R knockout (KO) mice under basal conditions and LPS treatment.

Endothelial transient receptor potential conical channel (TRPC)-3 activation induces vasogenic edema formation in the rat piriform cortex following status epilepticus.

Transient receptor potential canonical channel (TRPC) is a nonselective cation channel permeable to Ca(2+), which express in many cell types, including neurons. However the alterations in TRPC receptor expressions in response to status epilepticus (SE) have not been explored. Therefore, the present study was designated to elucidate the roles of TRPC3 in neuronal death and vasogenic edema within the rat piriform cortex (PC) following SE.

The effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampus.

Purpose: Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine. Because of little preclinical or clinical data concerning the outcomes of LEV in SE-induced neuronal death and vasogenic edema, we investigated the effect of LEV on SE-induced injury in comparison to diazepam (DZP), and valproate (VPA).

Methods: Two hours after pilocarpine-induced SE, rats were given one of the following drugs; (1) DZP, (2) LEV, (3) VPA, (4) DZP+LEV, (5) DZP+VPA, and (6) DZP+oxiracetam.

The reverse roles of transient receptor potential canonical channel-3 and -6 in neuronal death following pilocarpine-induced status epilepticus.

Transient receptor potential canonical channel (TRPC) is a nonselective cation channel permeable to Ca(2+), which is expressed in many cell types, including neurons. However, the alterations in TRPC receptor expressions in response to status epilepticus (SE) have not been explored. Therefore, the present study was designated to elucidate the roles of TRPC3 and TRPC6 in neuronal death following SE.

Interleukin-18 attenuates disruption of brain-blood barrier induced by status epilepticus within the rat piriform cortex in interferon-γ independent pathway.

Status epilepticus increases brain-blood barrier (BBB) permeability leading to vasogenic edema. This BBB disruption is usually confined within relatively limited cerebral regions including the piriform cortex (PC), and leads to epileptogenesis and contributes to progression of epilepsy. Although cytokines are at least partly responsible for changes in BBB permeability, the role of interleukin-18 (IL-18) in vasogenic edema is not yet explored in detail.

Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus.

Background: Status epilepticus (SE) induces severe vasogenic edema in the piriform cortex (PC) accompanied by neuronal and astroglial damages. To elucidate the mechanism of SE-induced vasogenic edema, we investigated the roles of tumor necrosis factor (TNF)-α in blood-brain barrier (BBB) disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced SE.

Methods: SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, and soluble TNF p55 receptor (sTNFp55R) prior to SE induction.

The roles of P2X7 receptor in regional-specific microglial responses in the rat brain following status epilepticus.

Recently, we have reported that astroglial activations in response to status epilepticus (SE) show regional-specific manners in the rat hippocampus. However, it is unknown that microglial responses to SE would show regional-specific patterns. Therefore, the present study was designed to elucidate the regional-specific microglial activation and relationship between P2X7 receptor functions and SE-induced microglial responses in the rat brain.

Up-regulation of endothelial endothelin-1 expression prior to vasogenic edema formation in the rat piriform cortex following status epilepticus.

Endothelin-1 (ET-1) is one of potential factors to induce vasogenic edema formation, since exogenous ET-1 treatment decreases aquaporin 4 (AQP4) expression and increases chemokines induction. To identify the role of endogenous ET-1 in vasogenic edema formation, we examined the correlation between endogenous ET-1 expression and vasogenic edema formation in the pirifom cortex following status epilepticus (SE). In the present study, SMI-71 (a brain-blood barrier marker) immunoreactivity was significantly reduced in blood vessels at 1 day after SE when vasogenic edema and neuronal damage were observed.

Changes in TWIK-related acid sensitive K+-1 and -3 channel expressions from neurons to glia in the hippocampus of temporal lobe epilepsy patients and experimental animal model.

In the present study, we analyzed expressions of tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ (TASK) channel-1 and -3 in the hippocampus of patients with temporal lobe epilepsy (TLE) and in rat model. In the control human subjects, TASK-1, and -3 immunoreactivity was observed in pyramidal neurons and dentate granule cells. In TLE patients, TASK-1 and -3 immunoreactivity was rarely observed in neurons.

P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus.

Background: The release of tumor necrosis factor-α (TNF-α) appears depend on the P2X7 receptor, a purinergic receptor. In the present study, we addressed the question of whether P2X7 receptor-mediated TNF-α regulation is involved in pathogenesis and outcome of status epilepticus (SE).

Methods: SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), A-438079, or A-740003 prior to SE induction.

p65/RelA-Ser529 NF-κB subunit phosphorylation induces autophagic astroglial death (Clasmatodendrosis) following status epilepticus.

Clasmatodendrosis is an irreversible astroglial degenerative change, which includes extensive swelling and vacuolization of cell bodies and disintegrated and beaded processes. This study was designed to elucidate whether clasmatodendrosis may be one of the autophagy-related degeneration of astrocytes. In this study, clasmatodendritic astrocytes were observed only in the stratum radiatum in the CA1 region.

The effects of electrical shock on the expressions of aquaporin subunits in the rat spinal cords.

We analyzed aquaporin (AQP) expression in the rat spinal cord following an electrical shock (ES) to elucidate the roles of AQP in spinal cord injury (SCI) induced by an electrical burn. In control animals, AQP1 immunoreactivity was observed in the small diameter dorsal horn fibers of laminae I and II and in astrocytes and neurons in the spinal cord. Both AQP4 and AQP9 immunoreactivity were detected in astrocytes.

Decrease in dystrophin expression prior to disruption of brain-blood barrier within the rat piriform cortex following status epilepticus.

Increased permeability of the brain-blood barrier (BBB) in the piriform cortex (PC) has been reported in various animal models of temporal lobe epilepsy. Since BBB disruption induced by epileptogenic insult has not fully clarified, we attempted to determine whether changes in BBB-related molecules are associated with vasogenic edema in the PC. One day after status epilepticus (SE), PC neurons and astrocytes showed a pyknotic nucleus and shrunken cytoplasm accompanied by vasogenic edema.

Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models.

Background: In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.

Results: Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level.

P2X7 receptor regulates leukocyte infiltrations in rat frontoparietal cortex following status epilepticus.

Background: In the present study, we investigated the roles of P2X7 receptor in recruitment and infiltration of neutrophil during epileptogenesis in rat epilepsy models.

Methods: Status epilepticus (SE) was induced by pilocarpine in rats that were intracerebroventricularly infused with either saline, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), or IL-1Ra (interleukin 1 receptor antagonist) prior to SE induction. Thereafter, we performed immunohistochemical studies for myeloperoxidase (MPO), CD68, interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2).

Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus.

In the present study we analyzed aquaporin-4 (AQP4) immunoreactivity in the piriform cortex (PC) and the hippocampus of pilocarpine-induced rat epilepsy model to elucidate the roles of AQP4 in brain edema following status epilepticus (SE). In non-SE-induced animals, AQP4 immunoreactivity was diffusely detected in the PC and the hippocampus. AQP4 immunoreactivity was mainly observed in the endfeet of astrocytes.

P2X7 receptor differentially modulates astroglial apoptosis and clasmatodendrosis in the rat brain following status epilepticus.

Recently, it has been reported that astroglial loss/dysfunction plays a role in epileptogenesis. In addition, astroglial loss is accompanied by up-regulation of P2X7 receptor expression in microglia. Therefore, we investigated whether P2X7 receptor is involved in astroglial damages induced by status epilepticus (SE).

Pyridoxal-5'-phosphate phosphatase/chronophin induces astroglial apoptosis via actin-depolymerizing factor/cofilin system in the rat brain following status epilepticus.

Actin-depolymerizing factor (ADF)/cofilin is a small cytoskeletal protein that is a stimulus-responsive mediator of actin dynamics. ADF/cofilin also translocates into mitochondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/cofilin translocations are negatively regulated by phosphorylation.

Pyridoxal-5'-phosphate phosphatase/chronophin inhibits long-term potentiation induction in the rat dentate gyrus.

Pyridoxal-5'-phosphate (PLP)-phosphatase/chronophin (PLPP/CIN) directly dephosphorylates actin-depolymerizing factor (ADF)/cofilin as well as PLP. Although PLPP/CIN plays a role in the regulation of F-actin and vitamin B(6) metabolism, there is no direct evidence to support a correlation between PLPP/CIN and F-actin polymerization during long-term potentiation (LTP) induction. In this study, we investigated whether the expression of PLPP/CIN is altered following LTP induction, and whether Tat-PLPP/CIN transduction affects LTP induction in the rat dentate gyrus (DG).

Transduced PEP-1-Grb7 fusion protein suppressed LPS-induced COX-2 expression.

Although the incidence and severity of atopic dermatitis (AD) is steadily increasing at an alarming rate, its pathogenic mechanisms remain poorly understood yet. Recently, we found that the expression of Grb7 protein was markedly decreased in AD patients using proteomic analysis. In the present study, human Grb7 gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-Grb7 fusion protein.

Human PEP-1-ribosomal protein S3 protects against UV-induced skin cell death.

The consequences of ultraviolet (UV) exposure are implicated in skin aging and cell death. The ribosomal protein S3 (rpS3) is one of the major proteins by which cells counteract the deleterious effects of UV and it plays a role in the repair of damaged DNA. In the present study, we investigated the protective effects of PEP-1-rpS3 fusion protein after UV-induced cell injury.