The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aß(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aß(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Acupuncture May Help to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Sham-Controlled, Single-Blind Study.

OBJECTIVE: This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC). METHODS: This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals. Secondary outcomes were total and subdomain scores on the Functional Assessment of Cancer Therapy-General (FACT-G), and scores on the FACT/GOG-Ntx subscale and the Brief Pain Inventory-Short Form (BPI-SF), at baseline, weeks 12, 36, and follow-up (week 48). RESULTS: Thirty-two patients met the inclusion criteria and received verum acupuncture (N = 16) or sham acupuncture (N = 16). Under the -intent-to-treat principle, 26 participants were analyzed. Significant changes from baseline for questionnaire scores and sensory NCV were observed in both study groups. Sham acupuncture was associated with significant reductions from baseline in motor NCV and sensory touch thresholds; no such changes were observed with verum acupuncture. No serious adverse events were reported. CONCLUSION: Prophylactic acupuncture may exert neuroprotective effects on mechanical or tactile touch thresholds during chemotherapy regimens in patients with CRC, with evidence of this protectiveness persisting at 6 months' follow-up. The lack of change in motor NCV values with verum acupuncture indicates neuroprotective effects. Sensory NCV values and patient-reported outcomes did not differ significantly between the study groups.

Stem bark chloroform extract of Bombax costatum Pellegr. & Vuillet exhibit anticonvulsant and neuroprotective effects in pentylenetetrazole-induced seizures in rats.

AIM OF THE STUDY: The study aimed at evaluating the potentials of stem bark extracts of Bombax costatum (B. costatum) on seizure, pentylenetetrazole (PTZ) induced kindling and associated changes in wistar albino rats. MATERIALS AND METHODS: Phase 1 evaluated which extract of B. costatum (chloroform, ethanol and n-hexane) is most effective in preventing seizure in acute PTZ-induced (85mg/kg) seizure in rats. Phase 2 evaluated the potentials of stem bark chloroform extract of B. costatum in PTZ-kindled rats at a dose 250 and 500mg/kg in comparison to diazepam. As its effects on memory, oxidative stress markers, neurotransmitters and brain histology were evaluated. Phase 3 determined the probable curative effects of B. costatum on fully kindled rats. RESULTS: In phase 1, Chloroform extract of B. coststum 500mg/kg is the most effective (P<0.05) in preventing seizure as compared to ethanol and n-hexane extracts. In phase 2, chloroform extract of B. costatum delayed the development of kindling, improved kindling associated cognitive impairment and alterations of glutamate and gamma-aminobutyric acid (GABA). Further, it attenuated oxidative stress besides the maintenance of neuronal architecture of the hippocampus. CONCLUSION: Conclusively, chloroform stem bark extract of B. costatum antagonizes PTZ-induced seizure progression, protects against kindling induced cognitive impairment and oxidative stress. Additionally, it also increases the brain level of GABA at high dose and prevented against kindling-induced hippocampal disruptions. Hence, this justifies its use traditionally in the treatment of epileptic seizures.

The Neuroprotective Effect Associated with Echinops spinosus in an Acute Seizure Model Induced by Pentylenetetrazole.

Echinops spinosus (ES) is a medicinal plant with a wide range of pharmacological and biological effects. It is a medicinal herb having a variety of therapeutic characteristics, including antioxidant, anti-inflammatory, and antibacterial capabilities. The primary goal of this research is to investigate the neuroprotective and anticonvulsant characteristics of E. spinosa extract (ESE) against pentylenetetrazole (PTZ)-induced acute seizures. Negative control rats, ESE treatment rats, PTZ acute seizure model rats, ESE + PTZ rats, and Diazepam + PTZ rats were used in the study. The rats were given a 7-day treatment. ESE pretreatment elevated the latency to seizure onset and lowered seizure duration after PTZ injection. By reducing Bax levels and enhancing antiapoptotic Bcl-2 production, ESE prevented the release of interleukin-1ß, tumor necrosis factor-α, and cyclooxygenase-2, as well as preventing hippocampal cell death after PTZ injection. ESE corrected the PTZ-induced imbalance in gamma-aminobutyric acid levels and increased the enzyme activity of Na+/K+-ATPase. Echinops spinosus is a potent neuromodulatory, antioxidant, antiinflammatory, and antiapoptotic plant that could be employed as a natural anticonvulsant in the future.

N-Acetyl Cysteine as a Neuroprotective Agent in Progressive Multiple Sclerosis (NACPMS) trial: Study protocol for a randomized, double-blind, placebo-controlled add-on phase 2 trial.

INTRODUCTION: Patients with progressive multiple sclerosis (PMS) experience relentless disability worsening. Current approved therapies have very modest effects on disability progression and purely focus on immunomodulation. While some inflammatory processes exist in non-active PMS, other biological processes such as neuronal injury from oxidative stress are likely more critical. N-acetyl cysteine (NAC) directly scavenges free radicals and restores neuronal glutathione, a major endogenous antioxidant. Our group has recently evaluated the safety of high dose NAC in a pilot trial in PMS with no tolerability concerns. We aim now to assess the safety, tolerability, and effect of NAC on progression of several MRI, clinical and biological markers in PMS patients. METHODS: The NACPMS trial is a multi-site, randomized, double-blind, parallel-group, placebo-controlled add-on phase 2 trial. Ninety-eight PMS patients with EDSS 3.0-7.0 and aged 40-70 years will be randomized to NAC 1200 mg TID or matching placebo (1:1) as an add-on to the standard of care stratified by site and disease type during a 15-month intervention period. It is hypothesized that a reduction in oxidative stress injury will lessen brain atrophy estimated by MRI. The primary outcome analysis will compare the percent change over 12 months (Month 15 vs Month 3) between treatment and control arms using multivariable linear regression adjusted by age, sex, and disease duration. ETHICS: This study was approved by the Institutional Review Board at the University of California, San Francisco (IRB21-34143), and an Investigational New Drug approval was obtained from the FDA (IND127184). TRIAL REGISTRATION: NCT05122559.

Multi-target neuroprotective effects of herbal medicines for Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. AIM OF THE STUDY: This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. MATERIALS AND METHODS: Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3ß). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. RESULTS: Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3ß inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. CONCLUSIONS: The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.

Failed, Interrupted, or Inconclusive Trials on Neuroprotective and Neuroregenerative Treatment Strategies in Multiple Sclerosis: Update 2015-2020.

In the recent past, a plethora of drugs have been approved for the treatment of multiple sclerosis (MS). These therapeutics are mainly confined to immunomodulatory or immunosuppressive strategies but do not sufficiently address remyelination and neuroprotection. However, several neuroregenerative agents have shown potential in pre-clinical research and entered Phase I to III clinical trials. Although none of these compounds have yet proceeded to approval, understanding the causes of failure can broaden our knowledge about neuroprotection and neuroregeneration in MS. Moreover, most of the investigated approaches are characterised by consistent mechanisms of action and proved convincing efficacy in animal studies. Therefore, learning from their failure will help us to enforce the translation of findings acquired in pre-clinical studies into clinical application. Here, we summarise trials on MS treatment published since 2015 that have either failed or were interrupted due to a lack of efficacy, adverse events, or for other reasons. We further outline the rationale underlying these drugs and analyse the background of failure to gather new insights into MS pathophysiology and optimise future study designs. For conciseness, this review focuses on agents promoting remyelination and medications with primarily neuroprotective properties or unconventional approaches. Failed clinical trials that pursue immunomodulation are presented in a separate article.

Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone.

Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

Role of natural products for the treatment of Alzheimer's disease.

Negative psychological and physiological consequences of neurodegenerative disorders represent a high social and health cost. Among the neurodegenerative disorders Alzheimer's disease (AD) is recognized as a leading neurodegenerative condition and a primary cause of dementia in the elderlys. AD is considered as neurodegenerative disorder that progressively impairs cognitive function and memory. According to current epidemiological data, about 50 milLion people worldwide are suffering from AD. The primary symptoms of AD are almost inappreciable and usually comprise forgetfulness of recent events. Numerous processes are involved in the development of AD, for example oxidative stress (OS) mainly due to mitochondrial dysfunction, intracellular the accumulation of hyperphosphorylated tau (τ) proteins in the form of neurofibrillary tangles, excessive the accumulation of extracellular plaques of beta-amyloid (Aß), genetic and environmental factors. Running treatments only attenuate symptoms and temporarily reduce the rate of cognitive progression associated with AD. This means that most treatments focus only on controlLing symptoms, particularly in the initial stages of the disease. In the past, the first choice of treatment was based on natural ingredients. In this sense, diverse natural products (NPs) are capable to decrease the symptoms and alleviate the development of several diseases including AD attracting the attention of the scientific community and the pharmaceutical industry. Specifically, numerous NPs including flavonoids, gingerols, tannins, anthocyanins, triterpenes and alkaloids have been shown anti-inflammatory, antioxidant, anti-amyloidogenic, and anti-choLinesterase properties. This review provide a summary of the pathogenesis and the therapeutic goals of AD. It also discusses the available data on various plants and isolated natural compounds used to prevent and diminish the symptoms of AD.

Anti-cerebral ischemia reperfusion injury of polysaccharides: A review of the mechanisms.

Cerebral ischemia-reperfusion injury can lead to a series of serious brain diseases and cause death or different degrees of disability. Polysaccharide is a kind of biological macromolecule with multiple pharmacological activities and has been proven that it may be used for the treatment of cerebral I/R injury in the future. By sorting out all relevant research from 2000 to 2020, we selected 74 references and identified 22 kinds of polysaccharides. Almost all of these polysaccharides are extracted from traditional Chinese medicine. Research shows that these polysaccharides can improve cerebral ischemia-reperfusion injury through anti-oxidative stress, inhibiting the neuroinflammation, glutamate neurotoxicity and neuronal apoptosis, and exerting neurotrophic effect. The specific mechanisms include clearing ROS and RNS, inhibiting the expression of inflammatory factors, maintaining mitochondrial homeostasis and blocking caspase cascade, regulating NMDA receptor and promoting angiogenesis. We hoped this review is instructive for researchers to design, research and develop polysaccharides.

Effect of L-Carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study.

L-Carnosine is an amino acid that acts as an anti-oxidant, anti-toxic and neuroprotective agent. There is a paucity of data about the effectiveness of L-Carnosine in the management of autism spectrum disorder (ASD) in children. This study aimed at investigating the effectiveness of L-Carnosine as adjunctive therapy in the management of ASD. This was a randomized controlled trial. Children aged 3-6 years with a diagnosis of mild to moderate ASD were assigned to standard care arm (occupational and speech therapy) and intervention care arm (L-Carnosine, 10-15 mg/kg in 2 divided doses) plus standard care treatment. The children were assessed at the baseline and the end of 2 months for the scores of Childhood Autism Rating Scale, Second Edition-Standard Version (CARS2-ST), Autism Treatment Evaluation Checklist (ATEC), BEARS sleep screening tool and 6-item Gastrointestinal Severity Index (6-GSI). Of the sixty-seven children enrolled, sixty-three children had completed the study. No statistically significant difference (p > 0.05) was observed for any of the outcome measures assessed. Supplementation of L-Carnosine did not improve the total score of CARS2-ST, ATEC, BEARS sleep screening tool and 6-GSI scores of children with ASD. Further investigations are needed with more objective assessments to critically validate the effectiveness of L-Carnosine on ASD children for more decisive results.

Salidroside as a potential neuroprotective agent for ischemic stroke: a review of sources, pharmacokinetics, mechanism and safety.

Salidroside (Sal) is a bioactive extract principally from traditional herbal medicine such as Rhodiola rosea L., which has been commonly used for hundreds of years in Asia countries. The excellent neuroprotective capacity of Sal has been illuminated in recent studies. This work focused on the source, pharmacokinetics, safety and anti-ischemic stroke (IS) effect of Sal, especially emphasizing its mechanism of action and BBB permeability. Extensive databases, including Pubmed, Web of science (WOS), Google Scholar and China National Knowledge Infrastructure (CNKI), were applied to obtain relevant online literatures. Sal exerts powerful therapeutic effects on IS in experimental models either in vitro or in vivo due to its neuroprotection, with significantly diminishing infarct size, preventing cerebral edema and improving neurological function. Also, the findings suggest the underlying mechanisms involve anti-oxidation, anti-inflammation and anti-apoptosis by regulating multiple signaling pathways and key molecules, such as NF-κB, TNF-α and PI3K/Akt pathway. In pharmacokinetics, although showing a rapid absorption and elimination, bioavailability of Sal is elevated under some non-physiological conditions. The component and its metabolite (tyrosol) are capable of distributing to brain tissue and the later keeps a higher level of concentration. Moreover, Sal scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials, but combination of drugs and perinatal use of medicine should be taken more attentions. Finally, as an active ingredient, not only is Sal isolated from diverse plants with limited yield, but also large batches of the products can be harvested by biological and chemical synthesis. With higher efficacy and better safety profiles, Sal could sever as a promising neuroprotectant for preventing and treating IS. Nevertheless, further investigations are still required to explore the pharmacodynamic and pharmacokinetic properties of Sal in the treatment of IS.

Ashwagandha in brain disorders: A review of recent developments.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders. AIM OF THE REVIEW: This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders. MATERIALS AND METHODS: All the information and data was collected on Ashwagandha using keywords "Ashwagandha" along with "Phytoconstituents", "Ayurvedic, Unani and Homeopathy marketed formulation", "Brain disorders", "Mechanism" and "Patents". Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies. RESULTS: Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising. CONCLUSION: The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.

Neuroprotective Agents as an Adjuvant Treatment in Patients With Acute Spinal Cord Injuries: A Qualitative Systematic Review of Randomized Trials.

STUDY DESIGN: This was a systematic literature review. OBJECTIVE: The objective of this study was to evaluate randomized clinical trials that address potential neuroprotective agents used to improve neurological outcome in patients with spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Clinical treatment of acute SCI has evolved significantly, but neurological recovery of severely injured patients remains modest. Neuroprotective agents may act to limit secondary damage in the sequence of pathophysiologic insults that occur after primary SCI. METHODS: We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines of all clinical randomized trials that evaluated potential neuroprotective agents (drugs, stem cells, and any type of medicative interventions) in neurological outcome of acute SCI. All the studies were graded according to their level of evidence in accordance with the Oxford Level of Evidence-based Medicine. RESULTS: A total of 16 randomized clinical trials were included and fully analyzed in our review. The following 12 substances/drugs were analyzed: methylprednisolone (MP), naloxone, tirilizad, nimodipine, Sygen, autologous incubated macrophages, autologous bone marrow cells, minocycline, erythropoietin, ganglioside, vitamin D, and progesterone. Modest benefits were attributed to minocycline and Sygen (without statistical significance), and some benefits were obtained with erythropoietin and progesterone plus vitamin D in neurological outcome. For MP, the benefits are also controversial and may be attributed to statistical artifacts and with a high risk of adverse effects. The other substances did not change the final outcome. All studies were considered as grade B of recommendation (100%) and levels of evidences as B2 (81.25%) and B3 (18.75%). CONCLUSIONS: Our review reported some potential substances that may improve neurological outcome in acute SCI: MP, vitamin D associated with progesterone, and erythropoietin. Their potential benefits were modest in the evaluated studies, requiring further randomized clinical trials with large samples of patients, without statistical artifacts, for routine clinical use. Furthermore, potential adverse effects must be considered with the use of neuroprotective agents in SCI. Until then, the use of these substances may be experimental or restricted to specific clinical situations.

Therapeutic Evaluation of Synthetic Peucedanocoumarin III in an Animal Model of Parkinson's Disease.

The motor and nonmotor symptoms of Parkinson's disease (PD) correlate with the formation and propagation of aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark of the disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses the ability to disaggregate ß sheet aggregate structures, including α-synuclein fibrils. This finding suggests that PCIII could be a therapeutic lead compound in PD treatment. However, the translational value of PCIII and its safety information have never been explored in relevant animal models of PD. Therefore, we first designed and validated a sequence of chemical reactions for the large scale organic synthesis of pure PCIII in a racemic mixture. The synthetic PCIII racemate facilitated clearance of repeated ß sheet aggregate (ß23), and prevented ß23-induced cell toxicity to a similar extent to that of purified PCIII. Given these properties, the synthetic PCIII's neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced PD mouse models. The PCIII treatment (1 mg/kg/day) in a 6-OHDA-induced PD mouse model markedly suppressed Lewy-like inclusions and prevented dopaminergic neuron loss. To evaluate the safety profiles of PCIII, high dose PCIII (10 mg/kg/day) was administered intraperitoneally to two-month-old mice. Following 7 days of PCIII treatment, PCIII distributed to various tissues, with substantial penetration into brains. The mice that were treated with high dose PCIII had no structural abnormalities in the major organs or neuroinflammation. In addition, high dose PCIII (10 mg/kg/day) in mice had no adverse impact on motor function. These findings suggest that PCIII has a relatively high therapeutic index. Given the favorable safety features of PCIII and neuroprotective function in the PD mouse model, it may become a promising disease-modifying therapy in PD to regulate pathogenic α-synuclein aggregation.

Does Nimodipine Interruption due to High Catecholamine Doses Lead to a Greater Incidence of Delayed Cerebral Ischemia in the Setting of Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: Current guidelines recommend the administration of nimodipine for the prevention of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, nimodipine can lead to significant drops in mean arterial pressure and cerebral perfusion pressure. Catecholamines are then used to maintain them while nimodipine is reduced and/or held. There is no evidence that nimodipine retains its neuroprotective effect at lower doses. We aimed to investigate the role of nimodipine interruption in the setting of aSAH and its possible impact on the incidence of DCI. METHODS: We performed a retrospective analysis in patients with aSAH admitted to our center from January 2012 to October 2015. Nimodipine prophylaxis duration and dosage and the incidence of DCI were recorded. Bivariate correlation with Spearman's rho (ρ) and ordinal regression analyses were performed. RESULTS: A total of 170 patients were included in the study. Of these, 165 (97.1%) received nimodipine prophylaxis starting on day 0. Nimodipine was interrupted in 85 of 165 (51.5%), whereas dose was reduced in 47 of 165 (28.5%); full dose was received by only 33 of 165 (20%). DCI was observed in 85 of 170 (50%). Nimodipine interruption correlated in a statistically significant way with a greater incidence of DCI (ρ = 0.431, P < 0.001); receiving full doses of nimodipine showed a statistically significant inverse correlation to DCI (ρ = -0.273, P < 0.001). Ordinal regression analysis revealed nimodipine interruption as a statistically significant independent predictor of DCI (odds ratio 0.194; 95% confidence interval 0.079-0.474, P < 0.001). CONCLUSIONS: Our analysis reveals a greater incidence of DCI in patients with aSAH when nimodipine is interrupted.

Natural Antioxidant Anthocyanins-A Hidden Therapeutic Candidate in Metabolic Disorders with Major Focus in Neurodegeneration.

All over the world, metabolic syndrome constitutes severe health problems. Multiple factors have been reported in the pathogenesis of metabolic syndrome. Metabolic disorders result in reactive oxygen species (ROS) induced oxidative stress, playing a vital role in the development and pathogenesis of major health issues, including neurological disorders Alzheimer's disease (AD) Parkinson's disease (PD). Considerable increasing evidence indicates the substantial contribution of ROS-induced oxidative stress in neurodegenerative diseases. An imbalanced metabolism results in a defective antioxidant defense system, free radicals causing inflammation, cellular apoptosis, and tissue damage. Due to the annual increase in financial and social burdens, in addition to the adverse effects associated with available synthetic agents, treatment diversion from synthetic to natural approaches has occurred. Antioxidants are now being considered as convincing therapeutic agents against various neurodegenerative disorders. Therefore, medicinal herbs and fruits currently receive substantially more attention as commercial sources of antioxidants. In this review, we argue that ROS-targeted therapeutic interventions with naturally occurring antioxidant flavonoid, anthocyanin, and anthocyanin-loaded nanoparticles might be the ultimate treatment against devastating illnesses. Furthermore, we elucidate the hidden potential of the neuroprotective role of anthocyanins and anthocyanin-loaded nanoparticles in AD and PD neuropathies, which lack sufficient attention compared with other polyphenols, despite their strong antioxidant potential. Moreover, we address the need for future research studies of native anthocyanins and nano-based-anthocyanins, which will be helpful in developing anthocyanin treatments as therapeutic mitochondrial antioxidant drug-like regimens to delay or prevent the progression of neurodegenerative diseases, such as AD and PD.

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.

Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.

A Systematic Review of Neuroprotective Efficacy and Safety of DL-3-N-Butylphthalide in Ischemic Stroke.

DL-3-n-butylphthalide (NBP) is widely used as a neuroprotective drug for ischemic stroke in China. There is, however, no established evidence on its efficacy and safety for patients with ischemic stroke. We, therefore, conducted a systematic review and meta-analysis. Major databases were searched to identify randomized controlled trials that assessed the efficacy and safety of NBP on ischemic stroke, reporting outcomes among patients treated with NBP alone or combined with standard anti-ischemic stroke drugs vs. standard anti-ischemic stroke drugs. Continuous data were validated, extracted and synthesized of standardized mean differences (SMDs) by random effects models, while dichotomous data were validated, extracted and synthesized of relative risk (RR) by random effects models. Twelve randomized controlled trials involving 1160 patients were identified. Results suggested that NBP monotherapy is not superior to standard anti-ischemic stroke drugs based on the Barthel Index (SMD, 0.25; 95% CI - 0.14 to 0.63; P=0.21 ) and the National Institutes of Health Stroke Scale (SMD, 0.73; 95% CI - 0.14 to 1.59; P=0.10 ). In contrast, the combination of NBP and standard anti-ischemic stroke drugs appears to be superior to standard drugs alone, again based on both the Barthel index (SMD, 1.65; 95% CI 1.25 to 2.04; P<0.01 ) and National Institutes of Health Stroke Scale (SMD, 1.40; 95% CI 0.72 to 2.09; P<0.01 ). However, the use of NBP may cause adverse event on the function of the liver (RR, 3.55; 95% CI 1.19 to 10.56; P<0.05 ). The combination use of NBP and standard anti-ischemic stroke drugs is more effective than standard drugs. However, more attention should be payed to the adverse effects on liver function. Our findings provided an established evidence of NBP as a neuroprotective drug, which may improve the current guideline for treatment of ischemic stroke.

Targets, Treatments, and Outcomes Updates in Diabetic Stroke.

GOAL: Due to multiple failures to translate basic research, the need for novel therapeutic targets and strategies is still urgent to save a larger number of the stroke patients' population and to reduce the toxicity of the current stroke therapy. METHOD: We summarize the most recent, within past 5 years, basic and clinical diabetic stroke research findings. FINDINGS: We aim to examine the most current understanding of stroke and neurovascular unit integrity, especially in presence of hyperglycemia and/or diabetes mellitus. From there, we are comparing the meaningful findings that aim at treating diabetic stroke to see where they differ, where they succeed, and where they open questions for new therapeutic strategies. CONCLUSION: The need for more clinically effective neuroprotective strategies is still mismatched with the bench side findings.