Prevention Of Neuronal Damage Research Articles

Effects of auriculotherapy on anxiety and biomarkers in Primary Health Care: a clinical trial.

to assess the effects of auriculotherapy on anxiety and brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) serum levels in adults assisted in Primary Health Care. a pre-experimental pilot clinical trial. Information was obtained from 19 patients using the State-Trait Anxiety Inventory (STAI) and analysis of BDNF, NSE and S100B serum levels. the pre-intervention anxiety score in the IDATE-Trait was 52.11±6.691 (CV 12.84%) and the assessment after auriculotherapy was significantly lower (43.72±8.141; CV 18.62%; P=0.0007). S100B levels were significantly reduced after auriculotherapy (from 64.03±72.18 to 54.03±68.53 pg/mL; CV 126.8%; P=0.0023). auriculotherapy effectively reduced anxiety levels. It proved to be safe and easy to apply, allowing nurses to perform this technique autonomously. A reduction of S100B was also evidenced, demonstrating possible prevention of neuronal damage.

Effect of selegiline as a monomine oxidase B inhibitor on the expression of neurotrophin mRNA levels in a contusion rat model of spinal cord injury

ABSTRACT Objective Spinal cord injury (SCI) is followed by a cascade of events at the site of injury, including vascular ischemia, an increase in free radicals, inflammation, and neuronal death. In these individuals, protection of nerves and supporting cells, as well as prevention of neuronal damage, may improve recovery opportunities. Neurotrophins are a family of polypeptides that regulate nerve differentiation, growth, and survival. Selegiline is a selective monoamine oxidase B (MAO-B) inhibitor used to treat Parkinson’s disease. Selegiline has been found to have neuroprotective properties and may be useful for the expression of neurotrophins. The aim of this study was to evaluate the expression levels of neurotrophin genes in spinal cord rats treated with selegiline. Methods Rats were divided into four groups: injury (control), laminectomy, sham (injured rat received 1 ml saline intraperitoneally) and treatment (injured rat received 5 mg/kg selegiline intraperitoneally for 7 days; once a day). The BBB scale (Basso, Beattie and Bresnahan) was performed once a week for 4 weeks to assess motor function after a spinal cord injury. On day 28 after SCI, the rat was sacrificed and the spinal cord lesion removed. A real-time PCR approach was used to assess neurotrophin gene expression. Results The results showed that administration of selegiline improves locomotor function and increases mRNA levels of BDNF, GDNF, NT-3, and NT-4. Conclusion In summary, the results of this study suggest that selegiline may be an appropriate treatment for spinal cord injuries.

Dose-dependent effects of a brain-penetrating iduronate-2-sulfatase on neurobehavioral impairments in mucopolysaccharidosis II mice

Deposition of heparan sulfate (HS) in the brain of patients with mucopolysaccharidosis II (MPS II) is believed to be the leading cause of neurodegeneration, resulting in several neurological signs and symptoms, including neurocognitive impairment. We recently showed that pabinafusp alfa, a blood-brain-barrier-penetrating fusion protein consisting of iduronate-2-sulfatase and anti-human transferrin receptor antibody, stabilized learning ability by preventing the deposition of HS in the CNS of MPS II mice. We further examined the dose-dependent effect of pabinafusp alfa on neurological function in relation to its HS-reducing efficacy in a mouse model of MPS II. Long-term intravenous treatment with low (0.1 mg/kg), middle (0.5 mg/kg), and high (2.0 mg/kg) doses of the drug dose-dependently decreased HS concentration in the brain and cerebrospinal fluid (CSF). A comparable dose-dependent effect in the prevention of neuronal damage in the CNS, and dose-dependent improvements in neurobehavioral performance tests, such as gait analysis, pole test, Y maze, and Morris water maze, were also observed. Notably, the water maze test performance was inversely correlated with the HS levels in the brain and CSF. This study provides nonclinical evidence substantiating a quantitative dose-dependent relationship between HS reduction in the CNS and neurological improvements in MPS II.

Astaxanthin: The possible effects of this carotenoid on disease, inflammation and aging control. A meta-analysis

Astaxanthin (ATX), a red pigment that belongs to the xanthophyll subclass of carotenoids, has a strong antioxidant ability and can eliminate singlet oxygen (O2-) as well as hydrogen peroxide (H2O2) and lipid peroxidation. ATX can also prevent mitochondrial dysfunction by permeating and co-localizing within the mitochondria and inhibit the release of cytochrome c resulting from mitochondrial permeabilization and, thus, prevent mitochondrial-mediated apoptotic cell death. Due to its antioxidant capacity and modulating properties of cell signaling, ATX exhibits a variety of beneficial biological activities among them protection against UV damage, anti-inflammatory and immunomodulatory activity, metabolic syndrome (MS) relief, cardioprotective effects, antidiabetic activity, prevention of neuronal damage, anti-aging and anticancer activity. The aim of the present study was to evaluate what has been published about ATX in PubMed/Medline between 2020-2021. The results were distributed in four Tables as follows: Table 1-Publication types; Table 2- Proposal for evaluating the article in vivo; Table 3- Cells markers used in clinical studies in vivo; Table 4- Astaxanthin in human clinical trial. We could observe that the interest of the scientific community has been growing in relation to the benefits of ATX. The results presented in the articles evaluated in this meta-analysis showed us that AXT is already a reality as an option in treatments for various diseases, including glaucoma, heart and vascular injury, type 2 diabetes and fatty liver. We conclude that ATX may not only be a promising nutraceutical as an ally to alternative treatments of the pathologies mentioned above, but also as a powerful prophylactic in elderly individuals in prevention of diseases associated with aging.

Potential Therapeutic Agent In Psychiatric And Neurological Diseases: Alpha Lipoic Acid

Alpha lipoic acid (ALA) which is known by its antioxidant properties can lead to positive reflections through various mechanisms of action in nervous system diseases. ALA can create privileges in the treatment of neurological and psychiatric diseases through the vital features such as prevention of formation of reactive oxygen species (ROS), having a mission as a cofactor in various enzyme complexes, promotion the level of antioxidants and neurotransmitters in brain. It has also been shown to be responsible for regulation the nerve growth factor, prevention of neuronal damage and neuronal loss, and vitalization of damaged tissues. Hence, the implementation of ALA as a therapeutic substance in the therapy of neurological and psychiatric diseases is promising in the treatment of diseases. Finally, ALA can prevent diseases related with nervous system.

Low back pain: possibilities of pathogenetic treatment

Intervertebral disc (IVD) degeneration is one of the major causes of low back pain (LBP). Due to the complexity of spinal pain syndromes, it is often difficult to determine the extent of the IVD's contribution to the genesis of spinal pain. Inflammatory response to IVD' injury has been acknowledged to be important in the process of disc degeneration and may play an important role in pain generation. In this article, the inflammatory mechanisms of LBP will be discussed with special focus on interactions between inflammatory mediators and IVD biomechanics. Tumor necrosis factor-α (TNF-α) is a key mediator of inflammatory reactions in the pathogenesis of degenerative disk disease. The role of TNF-α inhibitors as a potential target of therapeutic interventions in prevention of neuronal damage and neuroprotection in LBP is discussed.

Identification of Inflammatory Neuronal Injury and Prevention of Neuronal Damage in Multiple Sclerosis

Although multiple sclerosis (MS) has long been considered the prototype for an inflammatory, demyelinating disease of the central nervous system, modern histopathology and imaging techniques show that significant damage to neuronal structures already start occurring in the earliest stages of the disease. As the disease progresses, the extent of neuronal pathology accumulates. Therapeutic progress in terms of the prevention of increased disability has only just begun. To review possible diagnostic improvements of neuronal compartment pathology as well as direct therapeutic interventions based on reports from the last decade and outline clinical results from studies and perspectives on the progression of MS. Literature search focused on publications and the references contained therein, relating to neuronal compartment pathology and direct therapeutic interventions published in the last decade in well-established peer-reviewed journals. The quality of the cited works was ensured by their acceptance by peer review, participation in clinical trials, and authors' own expert assessment. Current MS therapies as well as medications that are in late phase 3 trials or under approval exhibit primarily anti-inflammatory properties. However, clinical and imaging data demonstrate the potential of using novel therapies to prevent neuronal damage. Whether these exhibit effects on the neuronal compartment due to interference with the immune system or additional direct effects depends without question on the specific mechanism of action. Combining anti-inflammatory and direct neuroprotective, neuroregenerative/repair therapy strategies may open up new avenues in the treatment of MS.

Changes in the expression of insulin-like growth factor 1 variants in the postnatal brain development and in neonatal hypoxia–ischaemia

Insulin-like growth factor-1 (IGF-1) is a multifunctional peptide of which numerous isoforms exist. The predominant form, IGF-1Ea is involved in physiological processes while IGF-1Ec (mechano-growth factor, MGF) is expressed in response to a different set of stimuli. We have identified specific changes in the expression patterns of these IGF-1 variants in brain development in normal rats and following neonatal hypoxia–ischaemia (HI). Both IGF-1Ea and IGF-1Ec are expressed during normal postnatal brain development, albeit with highly specific temporal distributions. In contrast, HI produced increased and prolonged expression of the IGF-1Ec isoform only. Importantly, hypoxia alone stimulated the expression of IGF-1Ec as well. Thus, IGF-1Ec may play a role in HI pathology. Neonatal hypoxia–ischaemia occurs in approximately 1:4000–1:10,000 newborns and causes neurological deficits in ∼75% of those affected. Unfortunately, no specific treatment is available. IGF-1 is known to have neuroprotective activity and its IGF-1Ec variant appears to be an endogenous protective factor in hypoxia–ischaemia. Therefore, IGF-1Ec could potentially be developed into a therapeutic modality for the attenuation or prevention of neuronal damage in this and related disorders.

Prevention of neuronal damage by calcium channel blockers with antioxidative effects after transient focal ischemia in rats

Background: Cerebral ischemia is a major leading cause of death and at the first place cause of disability all over the world. There are a lot of drugs that are in experimental stage for treatment of stroke. Among them are calcium channel blockers (CCBs) that have, in animal models, different effectiveness in healing of ischemic damage in brain. Mechanism of CCBs' action in cerebral ischemia is still unclear, but antioxidative property is supposed to be implicated. In the present study, we investigated antioxidative and neuroprotective properties of two CCBs, azelnidipine and amlodipine. Methods: Male Wistar Kyoto rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) by a nylon thread. Animals were divided into 3 groups, vehicle, azelnidipine and amlodipine group. In the azelnidipine and amlodipine groups, rats were treated with azelnidipine (1 mg/kg) and amlodipine (1 mg/kg) by gastric gavage for 2 weeks before MCAO. Vehicle group was treated by solution of methyl cellulose for 2 weeks. Rats were killed 24 h after MCAO. Physiological parameters (mean arterial pressure, heart rate, body weight), infarct volume, brain edema index, cerebral blood flow (CBF), oxidative stress markers which are HEL, 4-HNE, AGE and 8-OHdG, and evidence of apoptosis by TUNEL, were investigated. Results: There were no significant differences among groups in mean arterial pressure, heart rate and body weight. Treatment with azelnidipine and amlodipine reduced infarct volume and brain edema. Azelnidipine treated group showed more marked reduction of infarct volume and cerebral edema than amlodipine group. There was no attenuation of CBF in CCBs groups. The number of HEL, 4-HNE, AGE and 8-OHdG positive cells were significantly decreased in the CCBs treated groups. These molecules were again fewer in the azelnidipine group than in the amlodipine group. In TUNEL staining, the numbers of positive cells was smaller in the CCBs treated groups, especially in the azelnidipine group. Conclusions: Pretreatment of azelnidipine and amlodipine had a neuroprotective effect in ischemic brain. Antioxidative property is one of the important profiles of CCBs that is implicated in brain protection.

Ceramide in primary astrocytes from cerebellum: metabolism and role in cell proliferation.

Cerebellar astrocytes are equipped with an efficient molecular machinery able to control the levels, and possibly the subcellular location, of ceramide. The major metabolic routes that contribute to the maintenance and variation of the cellular ceramide include ceramide biosynthesis, by de novo pathway or sphingosine recycling, ceramide formation from complex sphingolipids degradation and ceramide catabolism. In cerebellar astrocytes from rat cerebellum a peculiar metabolism of sphingomyelin occurs. This includes the preponderance of acidic sphingomyelinase, paralleled by a deficiency of the neutral Mg2+-dependent enzyme, as well as the presence of an extra-Golgi form of sphingomyelin synthase, which shares many characteristics with PC-PLC. Moreover these cells are characterized by a high efficiency in converting sphingosine to ceramide, possibly functional to the role played by astrocytes in the prevention of neuronal damage by high sphingosine concentration. Recent evidence demonstrates that a change of ceramide level is one of the key steps in the chain of reactions elicited by mitogenic stimuli. In fact, low cellular levels of ceramide characterize, and appear to be required for, the proliferation of cerebellar astrocytes. In particular mitogenic stimuli, such as basic fibroblast growth factor (bFGF), rapidly down regulate the cellular levels of ceramide by stimulating sphingomyelin synthase. Ceramide acts as an intracellular physiological inhibitor of cell growth, being able to counteract the effect of bFGF by inhibiting the MAP kinase pathway. Although many questions remain in this field, the present knowledge strongly supports that ceramide represents a crucial member within lipid mediators, involved in the signaling pathways underlying cell proliferation in cerebellar astrocytes.

Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine

To investigate the in vivo role of NMDA receptor stimulation in HIV-1-related CNS neurotoxicity, we evaluated the neuroprotective potential of the NMDA receptor antagonist memantine in transgenic mice which have gp120-induced CNS damage. Brains of mice treated chronically with memantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for microtubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine treatment substantially decreased neuropathology in gp120 transgenic mice; this included statistically significant improvements in both dendritic and presynaptic terminal density. These results provide in vivo evidence that gp120 can activate neurotoxic pathways that can ultimately result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients.

4-(Tetrazolylalkyl)piperidine-2-carboxylic acids. Potent and selective N-methyl-D-aspartic acid receptor antagonists with a short duration of action

We have prepared a series of cis-4-(tetrazolylakyl)piperidine-2-carboxylic acids as potent and selective N-methyl-D-aspartic acid (NMDA) receptor antagonists. NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia. The compounds prepared were evaluated in vitro in both receptor binding assays [( 3H]CGS-19755, [3H]AMPA, and [3H]kainic acid) and in a cortical-wedge preparation (versus NMDA, quisqualic acid, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced convulsions in neonatal rats and NMDA-induced lethality in mice. The most potent compound of this series, 15 (LY233053), selectively displaced [3H]CGS-19755 binding with an IC50 of 107 +/- 7 nM and selectively antagonized responses due to NMDA in a cortical-wedge preparation with an IC50 of 4.2 +/- 0.4 microM. Compound 15 blocked both NMDA-induced convulsions in neonatal rats (minimum effective dose (MED) = 20 mg/kg ip) and NMDA-induced lethality in mice (MED = 5 mg/kg ip). This is the first example of an NMDA receptor antagonist that incorporates a tetrazole moiety as an omega-acid bioisostere. These amino acid antagonists are also unique from their phosphonic acid counterparts in that they have a shorter duration of action in vivo. For the treatment of acute disorders such as stroke, where an NMDA antagonist would be administered parenterally, the shorter duration of action may be beneficial, e.g., allowing for better dosage control. The combination of potent NMDA receptor antagonism and a short duration of action may make these compounds useful therapeutic agents in the treatment of a variety of neurological disorders.

Synthesis and pharmacology of a series of 3- and 4-(phosphonoalkyl)pyridine- and -piperidine-2-carboxylic acids. Potent N-methyl-D-aspartate receptor antagonists

We recently prepared a series of 3- and 4-(phosphonoalkyl)pyridine- and -piperidine-2-carboxylic acids as antagonists of neurotransmission at N-methyl-D-aspartate (NMDA) preferring receptors. NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia. The compounds prepared were evaluated for their ability to displace [3H]CPP binding (an assay shown to be selective for compounds that bind at the NMDA receptor) and for their ability to block NMDA-induced lethality in mice (an assay that is also specific for competitive and noncompetitive NMDA antagonists). Two of the compounds, cis-4-(phosphonomethyl)piperidine-2-carboxylic acid (11a) and cis-4-(3-phosphonoprop-1-yl)piperidine-2-carboxylic acid (11c) proved to be potent NMDA antagonists. 11a and 11c displaced [3H]CPP binding with IC50's of 95 and 120 nM, respectively, and both protected mice from NMDA-induced lethality, with MEDs (minimum effective dose, the dose at which three of the five animals tested survived) of 10 and 40 mg/kg ip, respectively. The rest of the compounds prepared were weakly active or inactive in these assays. The pattern of activity observed for this series parallels that observed for the acyclic series of omega-phosphono-alpha-amino acids, where AP5 and AP7 possessed NMDA antagonist activity while AP6 and AP8 were inactive. Reduction of conformational mobility by incorporation of the piperidine ring led to enhanced potency relative to the acyclic analogues.