We show that redox active iron can induce a regulated form of non-apoptotic cell death and tissue damage called ferroptosis that can contribute to secondary damage and functional loss in the acute and chronic periods after spinal cord injury (SCI) in young, adult, female mice. Phagocytosis of red blood cells at sites of hemorrhage is the main source of iron derived from hemoglobin after SCI. Expression of hemeoxygenase-1 that induces release of iron from heme, is increased in spinal cord macrophages 7 days after injury.
View Article and Find Full Text PDFToll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1 d, 7 d, and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wild-type mice.
View Article and Find Full Text PDFProlonged inflammation after spinal cord injury is detrimental to recovery. To find pharmacological modulators of the inflammation response, we designed a rapid drug screening paradigm in larval zebrafish followed by testing of hit compounds in a mouse spinal cord injury model. We used reduced linked green fluorescent protein (GFP) reporter gene expression as a read-out for reduced inflammation in a screen of 1081 compounds in larval zebrafish.
View Article and Find Full Text PDFIron accumulation in the CNS occurs in many neurological disorders. It can contribute to neuropathology as iron is a redox-active metal that can generate free radicals. The reasons for the iron buildup in these conditions are varied and depend on which aspects of iron influx, efflux, or sequestration that help maintain iron homeostasis are dysregulated.
View Article and Find Full Text PDFBackground: Sexual dysfunction is common but underestimated clinical symptom in MS patients. A growing body of evidence has been suggested the link between brain lesions and sexual dysfunction (SD) in patients with multiple sclerosis (MS). However, the clinical research investigating this relationship have shown inconsistent results.
View Article and Find Full Text PDFBackground: Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest.
View Article and Find Full Text PDFIron accumulation occurs in the central nervous system (CNS) in a variety of neurological conditions as diverse as spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, and others. Iron is a redox-active metal that gives rise to damaging free radicals if its intracellular levels are not controlled or if it is not properly sequestered within cells. The accumulation of iron occurs due to dysregulation of mechanisms that control cellular iron homeostasis.
View Article and Find Full Text PDFIschemic stroke is the second leading cause of mortality and disability globally. Neuronal damage following ischemic stroke is rapid and irreversible, and eventually results in neuronal death. In addition to activation of cell death signaling, neuroinflammation is also considered as another pathogenesis that can occur within hours after cerebral ischemia.
View Article and Find Full Text PDFIntroduction: Oxidative stress has recently emerged as a possible mechanism in the pathogenesis of epilepsy. Coenzyme Q10 (CoQ10) is a strong endogenous antioxidant that protects cells from lipid oxidation and Reactive Oxygen Species (ROS) production; however, the impact of CoQ10 on seizure characteristics in epileptic patients is unclear.
Methods: The current study enrolled patients with Epileptic Seizure (ES) to evaluate their serum concentration of CoQ10 and to investigate whether a relationship exists between CoQ10 levels with the duration, frequency, and type of seizure.
Objective: Thalamofrontal cortical network and limbic system are proposed to be involved in psychogenic nonepileptic seizure (PNES) and idiopathic generalized epilepsy (IGE). This study aimed to investigate neurochemical changes in prefrontal cortex, thalamus, and limbic circuits in patients with PNES and IGE. We also analyzed the interaction between cognitive functions and neurochemical changes in both groups.
View Article and Find Full Text PDFRecently, growing attention has been paid to the changes of brain biomarkers following the epilepsy. However, establishing specific epilepsy-related biomarkers has been impeded due to contradictory findings. This study systematically reviewed the evidence on brain biomarkers in epilepsy and determined reliable biomarkers in epileptic patients.
View Article and Find Full Text PDFCeruloplasmin (Cp) is a ferroxidase that also plays a role in iron efflux from cells. It can thus help to regulate cellular iron homeostasis. In the CNS, Cp is expressed as a membrane-anchored form by astrocytes.
View Article and Find Full Text PDFDisruption of prooxidant-antioxidant balance may lead to oxidative stress which is known as a mechanism contributing to ischemic stroke. Coenzyme Q10 (CoQ10) is an endogenous antioxidant that could be effective in preventing oxidative stress. However, the contribution of serum levels of CoQ10 in clinical neurological outcomes following ischemic stroke has not been clearly established.
View Article and Find Full Text PDFNecroptosis, a novel type of programmed cell death, has been recently implicated as a possible mechanism for cerebral ischemia-reperfusion (I/R) injury. We herein studied time-dependent changes of necroptosis markers along with apoptosis- and autophagy-associated proteins in rat hippocampus at 1, 3, 6, 12, 24, and 48 h after global cerebral I/R injury. Furthermore, to determine the cross talk between autophagy and necroptosis, we examined the effects of pretreatment with bafilomycin-A1 (Baf-A1), as a late-stage autophagy inhibitor, on necroptosis.
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