Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca) and other metal ions, such as zinc (Zn) and magnesium (Mg), into the cytosol. This Ca influx at the presynaptic terminal triggers the release of Zn and glutamate to the postsynaptic terminal.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP).

GAP-43 closely interacts with BDNF in hippocampal neurons and is associated with Alzheimer's disease progression.

Introduction: Growth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process.

Pathophysiological Roles of Transient Receptor Potential (Trp) Channels and Zinc Toxicity in Brain Disease.

Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels.

Engineered Mesenchymal Stem Cells Over-Expressing BDNF Protect the Brain from Traumatic Brain Injury-Induced Neuronal Death, Neurological Deficits, and Cognitive Impairments.

Traumatic brain injury (TBI) causes transitory or permanent neurological and cognitive impairments, which can intensify over time due to secondary neuronal death. However, no therapy currently exists that can effectively treat brain injury following TBI. Here, we evaluate the therapeutic potential of irradiated engineered human mesenchymal stem cells over-expressing brain-derived neurotrophic factor (BDNF), which we denote by BDNF-eMSCs, in protecting the brain against neuronal death, neurological deficits, and cognitive impairment in TBI rats.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes.

The Protective Role of Glutathione on Zinc-Induced Neuron Death after Brain Injuries.

Glutathione (GSH) is necessary for maintaining physiological antioxidant function, which is responsible for maintaining free radicals derived from reactive oxygen species at low levels and is associated with improved cognitive performance after brain injury. GSH is produced by the linkage of tripeptides that consist of glutamic acid, cysteine, and glycine. The adequate supplementation of GSH has neuroprotective effects in several brain injuries such as cerebral ischemia, hypoglycemia, and traumatic brain injury.

Acid Sphingomyelinase Inhibitor, Imipramine, Reduces Hippocampal Neuronal Death after Traumatic Brain Injury.

Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells.

Combined Treatment of Dichloroacetic Acid and Pyruvate Increased Neuronal Survival after Seizure.

During seizure activity, glucose and Adenosine triphosphate (ATP) levels are significantly decreased in the brain, which is a contributing factor to seizure-induced neuronal death. Dichloroacetic acid (DCA) has been shown to prevent cell death. DCA is also known to be involved in adenosine triphosphate (ATP) production by activating pyruvate dehydrogenase (PDH), a gatekeeper of glucose oxidation, as a pyruvate dehydrogenase kinase (PDK) inhibitor.

The Inhibition of Zinc Excitotoxicity and AMPK Phosphorylation by a Novel Zinc Chelator, 2G11, Ameliorates Neuronal Death Induced by Global Cerebral Ischemia.

AMP-activated protein kinase (AMPK) is necessary for maintaining a positive energy balance and essential cellular processes such as glycolysis, gene transcription, glucose uptake, and several other biological functions. However, brain injury-induced energy and metabolic stressors, such as cerebral ischemia, increase AMPK phosphorylation. Phosphorylated AMPK contributes to excitotoxicity, oxidative, and metabolic problems.

The Role of Zinc in Axon Formation via the mTORC1 Pathway.

Zinc is an essential micronutrient required for proper function during neuronal development because it can modulate neuronal function and structure. A fully functional description of zinc in axonal processing in the central nervous system remains elusive. Here, we define the role of intracellular zinc in axon formation and elongation, involving the mammalian target of rapamycin complex 1 (mTORC1).

Expression and Distribution of Free Zinc in Penile Erectile Tissue.

Purpose: Several studies have shown that zinc has a significant influence on erectile function. However, no studies evaluating the cellular distribution of free zinc in penile erectile tissue have been performed. Therefore, this study aimed to test whether free zinc is present in penile tissue and whether it may be involved in the electrical stimulation (ES)-induced penile erection.

Administration of an Acidic Sphingomyelinase (ASMase) Inhibitor, Imipramine, Reduces Hypoglycemia-Induced Hippocampal Neuronal Death.

Severe hypoglycemia (below 35 mg/dL) appears most often in diabetes patients who continuously inject insulin. To rapidly cease the hypoglycemic state in this study, glucose reperfusion was conducted, which can induce a secondary neuronal death cascade following hypoglycemia. Acid sphingomyelinase (ASMase) hydrolyzes sphingomyelin into ceramide and phosphorylcholine.

The Effects of Atorvastatin on Global Cerebral Ischemia-Induced Neuronal Death.

(1) Background and Purpose: Global cerebral ischemia-induced severe hypoxic brain damage is one of the main causes of mortality and long-term neurologic disability even after receiving early blood reperfusion. This study aimed to test the hypothesis that atorvastatin potentially has neuroprotective effects in global cerebral ischemia (GCI). (2) Methods: We performed two sets of experiments, analyzing acute (1-week) and chronic (4-week) treatments.

Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure.

Epilepsy is one of the most common and severe brain diseases. The exact cause of epilepsy is unclear. Epilepsy often occurs following brain damage, such as traumatic brain injury (TBI) and ischemia.

Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury.

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons.

The Transient Receptor Potential Melastatin 7 (TRPM7) Inhibitors Suppress Seizure-Induced Neuron Death by Inhibiting Zinc Neurotoxicity.

Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons.

Transient Receptor Potential Melastatin 2 (TRPM2) Inhibition by Antioxidant, -Acetyl-l-Cysteine, Reduces Global Cerebral Ischemia-Induced Neuronal Death.

A variety of pathogenic mechanisms, such as cytoplasmic calcium/zinc influx, reactive oxygen species production, and ionic imbalance, have been suggested to play a role in cerebral ischemia induced neurodegeneration. During the ischemic state that occurs after stroke or heart attack, it is observed that vesicular zinc can be released into the synaptic cleft, and then translocated into the cytoplasm via various cation channels. Transient receptor potential melastatin 2 (TRPM2) is highly distributed in the central nervous system and has high sensitivity to oxidative damage.

Artificial van der Waals hybrid synapse and its application to acoustic pattern recognition.

Brain-inspired parallel computing, which is typically performed using a hardware neural-network platform consisting of numerous artificial synapses, is a promising technology for effectively handling large amounts of informational data. However, the reported nonlinear and asymmetric conductance-update characteristics of artificial synapses prevent a hardware neural-network from delivering the same high-level training and inference accuracies as those delivered by a software neural-network. Here, we developed an artificial van-der-Waals hybrid synapse that features linear and symmetric conductance-update characteristics.

An Inhibitor of the Sodium-Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia.

Acidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium-hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellular sodium and hydrogen ions.

Graphene-assisted spontaneous relaxation towards dislocation-free heteroepitaxy.

Although conventional homoepitaxy forms high-quality epitaxial layers, the limited set of material systems for commercially available wafers restricts the range of materials that can be grown homoepitaxially. At the same time, conventional heteroepitaxy of lattice-mismatched systems produces dislocations above a critical strain energy to release the accumulated strain energy as the film thickness increases. The formation of dislocations, which severely degrade electronic/photonic device performances, is fundamentally unavoidable in highly lattice-mismatched epitaxy.

A Neuromorphic Device Implemented on a Salmon-DNA Electrolyte and its Application to Artificial Neural Networks.

A bioinspired neuromorphic device operating as synapse and neuron simultaneously, which is fabricated on an electrolyte based on Cu-doped salmon deoxyribonucleic acid (S-DNA) is reported. Owing to the slow Cu diffusion through the base pairing sites in the S-DNA electrolyte, the synaptic operation of the S-DNA device features special long-term plasticity with negative and positive nonlinearity values for potentiation and depression (α and α), respectively, which consequently improves the learning/recognition efficiency of S-DNA-based neural networks. Furthermore, the representative neuronal operation, "integrate-and-fire," is successfully emulated in this device by adjusting the duration time of the input voltage stimulus.

The Effects of Sodium Dichloroacetate on Mitochondrial Dysfunction and Neuronal Death Following Hypoglycemia-Induced Injury.

Our previous studies demonstrated that some degree of neuronal death is caused by hypoglycemia, but a subsequent and more severe wave of neuronal cell death occurs due to glucose reperfusion, which results from the rapid restoration of low blood glucose levels. Mitochondrial dysfunction caused by hypoglycemia leads to increased levels of pyruvate dehydrogenase kinase (PDK) and suppresses the formation of ATP by inhibiting pyruvate dehydrogenase (PDH) activation, which can convert pyruvate into acetyl-coenzyme A (acetyl-CoA). Sodium dichloroacetate (DCA) is a PDK inhibitor and activates PDH, the gatekeeper of glucose oxidation.

Carvacrol Attenuates Hippocampal Neuronal Death after Global Cerebral Ischemia via Inhibition of Transient Receptor Potential Melastatin 7.

Over the last two decades, evidence supporting the concept of zinc-induced neuronal death has been introduced, and several intervention strategies have been investigated. Vesicular zinc is released into the synaptic cleft, where it then translocates to the cytoplasm, which leads to the production of reactive oxygen species and neurodegeneration. Carvacrol inhibits transient receptor potential melastatin 7 (TRPM7), which regulates the homeostasis of extracellular metal ions, such as calcium and zinc.

Inhibition of NADPH Oxidase Activation by Apocynin Rescues Seizure-Induced Reduction of Adult Hippocampal Neurogenesis.

Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. Apocynin is known to be an inhibitor of NADPH (Nicotinamide adenine dinucleotide phosphate) oxidase activity and is highly effective in suppressing the production of superoxide. The neuroprotective effects of apocynin have been investigated in numerous brain injury settings, such as stroke, traumatic brain injury (TBI), and epilepsy.