Failure of therapeutic strategies for the management and recovery from traumatic spinal cord injury (SCI) is a serious concern. Dapsone (DDS) has been reported as a neuroprotective drug after SCI, although the phase after SC damage (acute or chronic) of its major impact on functional recovery has yet to be defined. Here, we evaluated DDS acute-phase anti-inflammatory effects and their impact on early functional recovery, one week after moderate SCI, and late functional recovery, 7 weeks thereafter.
View Article and Find Full Text PDFBackground: Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [F]FDG-PET analysis.
Methods: Wistar rats received KA (10 mg/kg, i.
Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental contamination by Tl has been reported in several countries, urging the need for studies to determine the impact of endogenous and exogenous mechanisms preventing thallium toxicity.
View Article and Find Full Text PDFObjective: Brain metabolic processes are not fully characterized in the kainic acid (KA)-induced Status Epilepticus (KASE). Thus, we evaluated the usefulness of F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an experimental strategy to evaluate in vivo, in a non-invasive way, the glucose consumption in several brain regions, in a semi-quantitative study to compare and to correlate with data from electroencephalography and histology studies.
Methods: Sixteen male Wistar rats underwent FDG-PET scans at basal state and after KA injection.
1-Methyl-4-phenylpyridinium ion (MPP)-induced neurotoxicity produces cellular damage resembling that encountered in Parkinson's disease. The mechanisms of cellular death after MPP include the participation of oxidative stress in the loss of dopaminergic neurons. Among the mechanisms of defense against oxidative stress, several copper-dependent proteins have been implicated: Cu/Zn-SOD, ceruloplasmin, and metallothionein.
View Article and Find Full Text PDFThe immature brain is especially vulnerable to lead (Pb) toxicity, which is considered an environmental neurotoxin. Pb exposure during development compromises the cognitive and behavioral attributes which persist even later in adulthood, but the mechanisms involved in this effect are still unknown. On the other hand, the kynurenine pathway metabolites are modulators of different receptors and neurotransmitters related to cognition; specifically, high kynurenic acid levels has been involved with cognitive impairment, including deficits in spatial working memory and attention process.
View Article and Find Full Text PDFEpilepsy is a neurological disorder characterized by recurrent spontaneous seizures due to an imbalance between cerebral excitability and inhibition, with a tendency towards uncontrolled excitability. Epilepsy has been associated with oxidative and nitrosative stress due to prolonged neuronal hyperexcitation and loss neurons during seizures. The experimental animal models report level of ATP diminished and increase in lipid peroxidation, catalase, and glutathione altered activity in the brain.
View Article and Find Full Text PDFEpilepsy is a neurological disorder of the central nervous system characterized by hypersynchronized neuronal activity and has been associated with oxidative stress. Oxidative stress interferes with the expression of genes as well as transcriptional factors such as nuclear factor-erythroid 2-related factor 2 (Nrf2). We evaluated the expression of Nrf2 in the rat brain in treated with kainic acid (KA) and pentylenetetrazole (PTZ).
View Article and Find Full Text PDFStatus epilepticus (SE) is a serious medical condition, as it may trigger epileptogenesis. SE produces continuous generalized seizures resulting in irreversible brain damage. Therefore, the use of neuroprotective agents to prevent cell damage, may reduce the impact of SE.
View Article and Find Full Text PDFAfter spinal cord injury (SCI), some self-destructive mechanisms start leading to irreversible neurological deficits. It is known that oxidative stress and apoptosis play a major role in increasing damage after SCI. Metallothioneins I and II (MT) are endogenous peptides with known antioxidant, neuroprotective capacities.
View Article and Find Full Text PDFMetallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I-IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons.
View Article and Find Full Text PDFEstradiol (E2), in addition to its known hormone function, is a neuroactive steroid that has shown neuroprotective profile in several models of neurological diseases. The present study explores the antioxidant effect of β-estradiol-3-benzoate (EB) on the neurotoxicity elicited by MPP in rat striatum. Male Wistar rats, that were gonadectomized 30days prior to EB, were given 100µgEB per rat every 48h for 11days and animals were infused with MPP via intrastriatal at day six after beginning EB treatment.
View Article and Find Full Text PDFEpilepsy is characterized by spontaneous recurrent seizures and temporal lobe epilepsy (TLE) is the most common serious neurological example of acquired and frequent epilepsy. Oxidative stress is recognized as playing a contributing role in several neurological disorders, and most recently have been implicated in acquired epilepsies. The MTs occur in several brain regions and may serve as neuroprotective proteins against reactive oxygen species causing oxidative damage and stress.
View Article and Find Full Text PDFBrain Res
September 2016
Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R).
View Article and Find Full Text PDFSpine J
April 2017
Background Context: Traumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions.
Purpose: Injection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy.
Environ Toxicol Pharmacol
September 2015
Epilepsy is a neurological disorder that has been associated with oxidative stress therefore epilepsy models have been develop such as kainic acid and pentylenetetrazol are usually used to understanding of the molecular mechanisms of this disease. We examined the metallothionein expression in rat brains of treated with kainic acid and pentylenetetrazol. Increase in metallothionein and nitrotirosyne immunoreactivity of both seizures epilepsy models was observed.
View Article and Find Full Text PDFIn developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reported in vitro and in situ cells.
View Article and Find Full Text PDFSpinal cord injury (SCI) is a condition producing irreversible damage to the neurological function. Among the leading mechanisms associated to cell death after SCI, excitotoxicity, oxidative stress, inflammatory response and apoptosis are considered potential targets to prevent tissue damage. We recently reported that dapsone an anti-inflammatory drug, decreases the activity of myeloperoxidase, lipid peroxidation, improve neurological function and increase the amount of spared tissue after SCI in rats.
View Article and Find Full Text PDFEpilepsy is considered one of the most common neurological disorders worldwide. Oxidative stress produced by free radicals may play a role in the initiation and progression of epilepsy; the changes in the mitochondrial and the oxidative stress state can lead mechanism associated with neuronal death pathway. Bioenergetics state failure and impaired mitochondrial function include excessive free radical production with impaired synthesis of antioxidants.
View Article and Find Full Text PDFAfter transient cerebral ischemia and reperfusion (I/R), damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II) protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats.
View Article and Find Full Text PDFCharacterization of auto-destructive mechanisms, leading to cell death after spinal cord injury (SCI) is important to prevent further damage to tissue. Heme oxygenase (HO) catalyzes the oxidation of heme to biliverdin and carbon monoxide (CO), as a response to cell damage. Products of HO action have biological effects, as antioxidant biliverdin.
View Article and Find Full Text PDFExcitotoxicity due to glutamate receptors (GluRs) overactivation is a leading mechanism of oxidative damage and neuronal death in various diseases. We have shown that dapsone (DDS) was able to reduce both neurotoxicity and seizures associated to the administration of kainic acid (KA), an agonist acting on AMPA/KA receptors (GluK1-GluK5). Recently, it has been shown that phenobarbital (PB) is also able to reduce epileptic activity evoked by that receptor.
View Article and Find Full Text PDFWe studied the use of three biocompatible materials obtained by plasma polymerization of pyrrole (PPy), pyrrole doped with iodine (PPy/I) and a copolymer formed with pyrrole and polyethylene glycol (PPy/PEG), implanted, separately, after a complete spinal cord transection in rats. Motor function assessed with the BBB scale and somatosensory evoked potentials (SEPs) in the implanted rats were studied. Results showed that the highest motor recovery was obtained in rats with PPy/I implants.
View Article and Find Full Text PDFLead (Pb), a ubiquitous and potent neurotoxicant, induces several neurophysiological and behavioural changes, while Pb alters the function of multiple organs and systems, it primarily affects the central nervous system. In human adults, encephalopathy resulting from Pb intoxication is often characterized by sleeplessness, poor attention span, vomiting, convulsions and coma; in children, Pb-induced encephalopathy is associated with mental dullness, vomiting, irritability and anorexia; diminished cognitive function resulting in a mental deficit has been also observed during Prolonged exposure to Pb. Pb can produce oxidative stress, disrupt the blood-brain barrier and alter several Ca(2+)-dependent processes, including physiological processes that involve nitric oxide synthesis on central nervous system in development and adult animals.
View Article and Find Full Text PDFAfter spinal cord injury (SCI), a complex cascade of pathophysiological processes rapidly damages the nervous tissue. The initial damage spreads to the surrounding tissue by different mechanisms, including oxidative stress. We have recently reported that the induction of metallothionein (MT) protein is an endogenous rapid-response mechanism after SCI.
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