Efficacy of a High-Protein Diet to Lower Glycemic Levels in Type 2 Diabetes Mellitus: A Systematic Review.

Diabetes is a metabolic disease with a high worldwide prevalence and an important factor in mortality and disability in the population. Complications can be reduced or prevented with lifestyle changes in physical activity, dietary habits, and smoking cessation. High-protein diets (HPDs, >30% or >1.0 g/Kg/day) decrease hyperglycemia in part due to their content of branched-chain amino acids (BCAAs), mainly leucine. Leucine (and other BCAAs) improve glucose metabolism by directly signaling in the medio-basal hypothalamus (MBH), increasing liver insulin sensitivity. To determine the effectiveness of an HPD to lower hyperglycemia, we analyzed the results of published clinical studies focusing on the levels of fasting plasma glucose and/or glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). We carried out a systematic search for clinical studies using HPDs. We searched five databases (Scopus, Web of Science, PubMed, Epistemonikos, and Cochrane), collecting 179 articles and finally selecting 8 articles to analyze their results. In conclusion, HPDs are an effective alternative to reduce hyperglycemia in patients with T2DM, especially so-called Paleolithic diets, due to their higher-quality protein from animal and vegetal sources and their exclusion of grains, dairy products, salt, refined fats, and added sugars.

Ethylene Elimination Using Activated Carbons Obtained from Baru (Dipteryx alata vog.) Waste and Impregnated with Copper Oxide.

Ethylene is a plant hormone regulator that stimulates chlorophyll loss and promotes softening and aging, resulting in a deterioration and reduction in the post-harvest life of fruit. Commercial activated carbons have been used as ethylene scavengers during the storage and transportation of a great variety of agricultural commodities. In this work, the effect of the incorporation of copper oxide over activated carbons obtained from baru waste was assessed. Samples were characterized by X-ray diffraction (XRD), N2 adsorption-desorption at -196 °C, field-emission scanning electron microscopy (FESEM) coupled with energy-dispersive X-ray spectroscopy (EDS), and infrared (IR) spectroscopy. The results showed that the amount of ethylene removed using activated carbon obtained from baru waste and impregnated with copper oxide (1667 µg g-1) was significantly increased in comparison to the raw activated carbon (1111 µg g-1). In addition, carbon impregnated with copper oxide exhibited better adsorption performance at a low ethylene concentration. Activated carbons produced from baru waste are promising candidates to be used as adsorbents in the elimination of ethylene during the storage and transportation of agricultural commodities at a lower cost.

Morin improves learning and memory in healthy adult mice.

BACKGROUND: Morin is a flavonoid found in many edible fruits. The hippocampus and entorhinal cortex play crucial roles in memory formation and consolidation. This study aimed to characterize the effect of morin on recognition and space memory in healthy C57BL/6 adult mice and explore the underlying molecular mechanism. METHODS: Morin was administered i.p. at 1, 2.5, and 5 mg/kg/24 h for 10 days. The Morris water maze (MWM), novel object recognition, novel context recognition, and tasks were conducted 1 day after the last administration. The mice's brains underwent histological characterization, and their protein expression was examined using immunohistochemistry and Western blot techniques. RESULTS: In the MWM and novel object recognition tests, mice treated with 1 mg/kg of morin exhibited a significant recognition index increase compared to the control group. Besides, they demonstrated faster memory acquisition during MWM training. Additionally, the expression of pro-brain-derived neurotrophic factor (BDNF), BDNF, and postsynaptic density protein 95 proteins in the hippocampus of treated mice showed a significant increase. In the entorhinal cortex, only the pro-BDNF increased. Morin-treated mice exhibited a significant increase in the hippocampus's number and length of dendrites. CONCLUSION: This study shows that morin improves recognition memory and spatial memory in healthy adult mice.

Anti-Inflammatory Effects of Flavonoids in Common Neurological Disorders Associated with Aging.

Aging reduces homeostasis and contributes to increasing the risk of brain diseases and death. Some of the principal characteristics are chronic and low-grade inflammation, a general increase in the secretion of proinflammatory cytokines, and inflammatory markers. Aging-related diseases include focal ischemic stroke and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Flavonoids are the most common class of polyphenols and are abundantly found in plant-based foods and beverages. A small group of individual flavonoid molecules (e.g., quercetin, epigallocatechin-3-gallate, and myricetin) has been used to explore the anti-inflammatory effect in vitro studies and in animal models of focal ischemic stroke and AD and PD, and the results show that these molecules reduce the activated neuroglia and several proinflammatory cytokines, and also, inactivate inflammation and inflammasome-related transcription factors. However, the evidence from human studies has been limited. In this review article, we highlight the evidence that individual natural molecules can modulate neuroinflammation in diverse studies from in vitro to animal models to clinical studies of focal ischemic stroke and AD and PD, and we discuss future areas of research that can help researchers to develop new therapeutic agents.

Synthesis of BiOI/Mordenite Composites for Photocatalytic Treatment of Organic Pollutants Present in Agro-Industrial Wastewater.

Recently, bismuth oxyiodide (BiOI) is an attractive semiconductor to use in heterogeneous photocatalysis processes. Unfortunately, BiOI individually shows limited photocatalytic efficiency, instability, and a quick recombination of electron/holes. Considering the practical application of this semiconductor, some studies show that synthetic zeolites provide good support for this photocatalyst. This support material permits a better photocatalytic efficiency because it prevents the quick recombination of photogenerated pairs. However, the optimal conditions (time and temperature) to obtain composites (BiOI/ synthetic zeolite) with high photocatalytic efficiency using a coprecipitation-solvothermal growth method have not yet been reported. In this study, a response surface methodology (RSM) based on a central composite design (CCD) was applied to optimize the synthesis conditions of BiOI/mordenite composites. For this purpose, eleven BiOI/mordenite composites were synthesized using a combined coprecipitation-solvothermal method under different time and temperature conditions. The photocatalytic activities of the synthesized composites were evaluated after 20 min of photocatalytic oxidation of caffeic acid, a typical organic pollutant found in agro-industrial wastewater. Moreover, BiOI/mordenite composites with the highest and lowest photocatalytic activity were physically and chemically characterized using nitrogen adsorption isotherms, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and diffuse reflectance spectroscopy (DRS). The optimal synthesis conditions prove to be 187 °C and 9 h. In addition, the changes applied to the experimental conditions led to surface property modifications that influenced the photocatalytic degradation efficiency of the BiOI/mordenite composite toward caffeic acid photodegradation.

Diet-Induced Metabolic Dysfunction of Hypothalamic Nutrient Sensing in Rodents.

A sedentary lifestyle and excessive nutrient intake resulting from the consumption of high-fat and calorie-rich diets are environmental factors contributing to the rapid growth of the current pandemic of type 2 diabetes mellitus (DM2). Fasting hyperglycemia, an established hallmark of DM2, is caused by excessive production of glucose by the liver, resulting in the inability of insulin to suppress endogenous glucose production. To prevent inappropriate elevations of circulating glucose resulting from changes in nutrient availability, mammals rely on complex mechanisms for continuously detecting these changes and to respond to them with metabolic adaptations designed to modulate glucose output. The mediobasal hypothalamus (MBH) is the key center where nutritional cues are detected and appropriate modulatory responses are integrated. However, certain environmental factors may have a negative impact on these adaptive responses. For example, consumption of a diet enriched in saturated fat in rodents resulted in the development of a metabolic defect that attenuated these nutrient sensing mechanisms, rendering the animals prone to developing hyperglycemia. Thus, high-fat feeding leads to a state of "metabolic disability" in which animals' glucoregulatory responses fail. We postulate that the chronic faltering of the hypothalamic glucoregulatory mechanisms contributes to the development of metabolic disease.

Highly sensitive and selective detection of glutathione using ultrasonic aided synthesis of graphene quantum dots embedded over amine-functionalized silica nanoparticles.

Glutathione (GSH) is the most abundant antioxidant in the majority of cells and tissues; and its use as a biomarker has been known for decades. In this study, a facile electrochemical method was developed for glutathione sensing using voltammetry and amperometry analyses. In this study, a novel glassy carbon electrode composed of graphene quantum dots (GQDs) embedded on amine-functionalized silica nanoparticles (SiNPs) was synthesized. GQDs embedded on amine-functionalized SiNPs were physical-chemically characterized by different techniques that included high resolution-transmission electron microscopy (HR-TEM), X-ray diffraction spectroscopy (XRD), UV-visible spectroscopy, Fourier-transform infrared spectroscopy(FTIR), and Raman spectroscopy. The newly developed electrode exhibits a good response to glutathione with a wide linear range (0.5-7 µM) and a low detection limit (0.5 µM) with high sensitivity(2.64 µA µM-1). The fabricated GQDs-SiNPs/GC electrode shows highly attractive electrocatalytic activity towards glutathione detection in the neutral media at low potential due to a synergistic surface effect caused by the incorporation of GQDs over SiNPs. It leads to higher surface area and conductivity, improving electron transfer and promoting redox reactions. Besides, it provides outstanding selectivity, reproducibility, long-term stability, and can be used in the presence of interferences typically found in real sample analysis.

Development of an electrochemical enzyme-free glucose sensor based on self-assembled Pt-Pd bimetallic nanosuperlattices.

The huge demand for the clinical diagnosis of diabetes mellitus has prompted the development of great-performance sensing platforms for glucose detection. Non-enzymatic glucose sensors are getting closer to their use in realistic applications. In this work, polyvinylpyrrolidone (PVP)-conjugated bimetallic Pt-Pd nanosuperlattices were synthesized precisely through a simple synthesis procedure, leading to controllable spherical morphologies with significantly fine and precise nanostructures in a size range of ∼3-5 nm by the reduction of Pt and Pd precursors in ethylene glycol, using an ultrasonic method. High-resolution transmission electron microscopy (HRTEM) measurements evidenced the formation of Pt-Pd bimetallic nanosuperlattices (BMNSLs). The superlattice-fringe patterns (111) of bimetallic Pt-Pd NSLs were identified in the HRTEM images, clearly showing their crystalline nature. The prepared material was used in the electrochemical oxidation of glucose using voltammetry analyses. The experimental evidence indicates that the Pt-Pd BMNSL modified glassy carbon electrode is effective for the selective amperometric detection of glucose in the presence of galactose, sucrose, fructose, lactose, and ascorbic acid. Moreover, its application in the detection of glucose in real serum and urine samples was assessed and good recoveries are achieved. The results show that a Pt-Pd bimetallic nanosuperlattice with high surface area, catalytic activity, and superior selectivity could be a promising material in the generation of novel electrodes for low-cost non-enzymatic glucose sensors.

Physiopathology of ischemic stroke and its modulation using memantine: evidence from preclinical stroke.

Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the brain. In this disease, two different damage areas are identifying: the lesion core, in which cells quickly die; and the penumbra (surrounding the lesion core), in which cells are functionally weakened but may recover and restore their functions. The currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy, but they have a short therapeutic window (4.5 and 6 hours after stroke onset, respectively) and a low percentage of stroke patients actually receive these treatments. Memantine is an approved drug for the treatment of Alzheimer's disease. Memantine is a noncompetitive, low affinity and use-dependent antagonist of N-methyl-D-aspartate glutamate receptor. Memantine has several advantages over developing a new drug to treat focal ischemic stroke, but the most important is that it has sufficient safe probes in preclinical models and humans, and if the preclinical studies provide more evidence about pharmacological actions in tissue protection and repair, this could help to increase the number of clinical trials. The present review summarizes the physiopathology of isquemic stroke and the pharmacological actions in neuroprotection and neuroplasticity of memantine in the post stroke stage of preclinical stroke models, to illustrate their potential to improve functional recovery in human patients.

The content of gonadotropin-releasing hormone (GnRH), kisspeptin, and estrogen receptors (ERα/ERß) in the anteromedial hypothalamus displays daily variations throughout the rat estrous cycle.

The content of gonadotropin-releasing hormone (GnRH), its mRNA, and estrogen receptor alpha (ERα) and beta (ERß) in the hypothalamus varies throughout the estrous cycle. Furthermore, the abundance of these molecules displays asymmetry between the right and left side. In the present study, we investigated the changes in the content of ERα, ERß, kisspeptin, and GnRH by western blot in the left and right anteromedial hypothalamus, at four different times during each stage of the rat estrous cycle. The serum levels of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also measured. ERα and ERß levels changed depending on the stage of the estrous cycle, meanwhile that of kisspeptin was modified according to both the hour of the day and the stage of the cycle. Except in estrus day, ERß was higher in the right hypothalamus, while ERα was similar in both sides. During both proestrus and estrus, the content of kisspeptin and GnRH was higher in the right hypothalamus. The highest levels of FSH and LH occurred at 17:00 h of proestrus. But at estrus, the highest FSH levels were observed at 08:00 h and the lowest at 17:00 h. Thus, the current results show that the content of ERα, ERß, kisspeptin, and GnRH in the anteromedial hypothalamus are regulated as a function of the stage of the estrous cycle and the hour of the day. Furthermore, the content of these proteins is regularly higher in the right anteromedial hypothalamus, regardless of the stage of the cycle or time of the day.

Enhancement of ciprofloxacin degradation in aqueous system by heterogeneous catalytic ozonation.

Fluoroquinolones are extensively used in medicine due to their antimicrobial activity. Their presence in water inhibits microorganism activity in conventional wastewater treatment plants. This study aims to evaluate the technical feasibility of applying heterogeneous catalytic ozonation to eliminate ciprofloxacin (CIP) as a representative of fluoroquinolone antibiotics normally present in municipal wastewater discharges. Experiments were conducted in a semi-batch stirred slurry reactor, using 0.7 L of 100 mg L-1 CIP aqueous solution, at pH 3 and 30 °C. Experimental results show that single ozonation can easily oxidise CIP molecules (68%) within the first 5 min, leading to the generation of refractory oxidation by-products. However, when heterogeneous catalytic ozonation is applied using iron oxide supported on MFI synthetic zeolite, total degradation of CIP is observed at 5 min and a higher mineralisation rate is obtained. A novel sequential process is developed for CIP mineralisation. In a first step, a flash single ozonation is applied and CIP molecules are broken down. Then, a catalytic ozonation step is conducted by adding the Fe/MFI catalyst into the reactor. As a result of catalyst addition, 44% of Total Organic Carbon (TOC) is eliminated within the first 15 min, compared to single ozonation where only 13% of TOC removal is reached in the same time. The application of this sequential process to a real wastewater effluent spiked with CIP leads to 52% of TOC removal.

Preclinical Research of Dihydromyricetin for Brain Aging and Neurodegenerative Diseases.

Brain aging and neurodegenerative diseases share the hallmarks of slow and progressive loss of neuronal cells. Flavonoids, a subgroup of polyphenols, are broadly present in food and beverage and numerous studies have suggested that it could be useful for preventing or treating neurodegenerative diseases in humans. Dihydromyricetin (DHM) is one of the main flavonoids of some Asian medicinal plants that are used to treat diverse illness. The effects of DHM have been studied in different in vitro systems of oxidative damage and neuroinflammation, as well as in animal models of several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Here we analyzed the most important effects of DHM, including its antioxidant, anti-inflammatory, and neuroprotective effects, as well as its ability to restore GABA neurotransmission and improve motor and cognitive behavior. We propose new areas of research that might contribute to a better understanding of the mechanism of action of this flavonoid, which could help develop a new therapy for aging and age-related brain diseases.

Simultaneous electrochemical determination of dopamine and epinephrine using gold nanocrystals capped with graphene quantum dots in a silica network.

Gold nanocrystals (AuNCs) were synthesized by economical and green strategy in aqueous medium by using N[3(trimethoxysilyl)propyl]ethylenediamine (TMSPED) as both a reducing and stabilizing mediator to avoid the aggregation of gold nanocrystals. Then, the AuNCs were capped with graphene quantum dots (GQDs) using an ultrasonic method. The resulting nanocomposites of GQD-TMSPED-AuNCs were characterized by X-ray photoelectron, X-ray diffraction, Raman, UV-vis and FT-IR spectroscopies. The size and shape of the nanocomposites were confirmed by using transmission electron microscopy and atomic force microscopy. The GQD-TMSPED-AuNCs placed on a glassy carbon electrode enable simultaneous determination of dopamine (DA) and epinephrine (EP) with peak potentials at 0.21 and 0.30 V (vs. Ag/AgCl). The response is linear in the 5 nM - 2.1 µM (DA) and 10 nM - 4.0 µM (EP) concentration ranges, with detection limits of 5 and 10 nM, respectively. The sensor shows good selectivity toward DP and EP in the presence of other molecules, facilitating its rapid detection in practical applications. Graphical abstract Schematic representation of gold nanocrystals capped with graphene quantum dots in the modified electrodes for simultaneous detection of dopamine and epinephrine.

Chemoinformatic Analysis of Selected Cacalolides from Psacalium decompositum (A. Gray) H. Rob. & Brettell and Psacalium peltatum (Kunth) Cass. and Their Effects on FcεRI-Dependent Degranulation in Mast Cells.

Cacalolides are a kind of sesquiterpenoids natural compounds synthesized by Psacalium decompositum (A. Gray) H. Rob. & Brettell or Psacalium peltatum (Kunth) Cass. Antioxidant and hypoglycemic effects have been found for cacalolides such as cacalol, cacalone or maturine, however, their effects on inflammatory processes are still largely unclear. The main aim of this study was to investigate the biological activities of secondary metabolites from P. decompositum and P. peltatum through two approaches: (1) chemoinformatic and toxicoinformatic analysis based on ethnopharmacologic background; and (2) the evaluation of their potential anti-inflammatory/anti-allergic effects in bone marrow-derived mast cells by IgE/antigen complexes. The bioinformatics properties of the compounds: cacalol; cacalone; cacalol acetate and maturin acetate were evaluated through Osiris DataWarrior software and Molinspiration and PROTOX server. In vitro studies were performed to test the ability of these four compounds to inhibit antigen-dependent degranulation and intracellular calcium mobilization, as well as the production of reactive oxygen species in bone marrow-derived mast cells. Our findings showed that cacalol displayed better bioinformatics properties, also exhibited a potent inhibitory activity on IgE/antigen-dependent degranulation and significantly reduced the intracellular calcium mobilization on mast cells. These data suggested that cacalol could reduce the negative effects of the mast cell-dependent inflammatory process.

Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats.

Maternal smoking with obligatory nicotine inhalation is associated with preterm delivery, low birth weight, fetal growth retardation and developmental defects. We tested the hypothesis that cigarette smoking-relevant nicotine inhalation during pregnancy impairs cardiovascular function and uterine hemodynamics with consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine via a novel lung alveolar region-targeted aerosol method produced nicotine pharmacokinetics resembling cigarette smoking in humans. This clinically relevant nicotine aerosol inhalation (NAI) induced transient reduction and irregular fluctuations in uterine artery blood flow associated with cardiac arrhythmia and high magnitude irregular fluctuations of systemic blood pressure. The arrhythmia included sinoatrial (SA) block, sinus arrest, 2° and 3° atrioventricular (A-V) block and supraventricular escape rhythm. These effects were blocked by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine. Resection of the ovarian nerve, which innervates uterine blood vessels, counteracted the NAI-induced reduction in uterine blood flow. We suggest that the rapid rise pattern of arterial blood nicotine concentration stimulates and then desensitizes autonomic nAChRs leading to disruptions of cardiac function as well as systemic and uterine hemodynamics that reduces uteroplacental blood flow, a mechanism underlying maternal smoking-associated pregnancy complications and developmental disorders. These findings challenge the safety of pure nicotine inhalation, i.e., E-cigarettes.

Toluene, Methanol and Benzaldehyde Removal from Gas Streams by Adsorption onto Natural Clay and Faujasite-Y type Zeolite.

A great number of pollution problems come as a result of the emission of Volatile Organic Compounds (VOCs) into the environment and their control becomes a serious challenge for the global chemical industry. Adsorption is a widely used technique for the removal of VOCs due to its high efficiency, low cost, and convenient operation. In this study, the feasibility to use a locally available clay, as adsorbent material to control VOCs emissions is evaluated. Natural clay is characterised by different physical-chemical methods and adsorptive interaction features between VOCs and natural clay are identified. Toluene (T), methanol (M) and benzaldehyde (B) are used here as representatives of three different kinds of VOCs. Adsorption isotherms onto natural clay and faujasite-Y type zeolite (Fau Y) are obtained at room temperature. According to Langmuir model data, maximum adsorption capacities (qm) of Fez natural clay and zeolite toward methanol (M), toluene (T) and benzaldehyde (B) at 300 K are 8, 0.89 and 3.1 mmol g-1, and 15, 1.91 and 13.9 mmol g-1 respectively. In addition, the effect of temperature on the adsorption of toluene onto natural clay is evaluated in the range from 300 to 323K. An increase on temperature reduces the adsorption capacity of natural clay toward toluene, indicating that an exothermic physical adsorption process takes place. The enthalpy of adsorption of toluene onto Fez natural clay was found to be -54 kJ mol-1. A preliminary cost analysis shows that natural clay could be used as an alternative low cost adsorbent in the control of VOCs from contaminated gas streams with a cost of US$ 0.02 kg-1 compared to Fau Y zeolite with US$ 10 kg-1.

The Role of Neuroinflammation in Age-Related Dementias.

The most common dementias such as Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia are associated with a decline in cognitive and social abilities. Although the molecular mechanisms of tissue damage in these dementias are not completely understood, these neurodegenerative illnesses share certain alterations such as neuroinflammation and gliosis. Increasing evidence suggests that microgliosis and astrogliosis play a key role in neuroinflammation observed in these dementias. Here we provide an overview of the participation of microglia and astrocytes in the neuroinflammatory response in common dementias.

Application of high silica zeolite ZSM-5 in a hybrid treatment process based on sequential adsorption and ozonation for VOCs elimination.

In this study, a hydrophobic synthetic zeolite, namely ZSM-5 is chosen as an adsorbent/catalyst for toluene removal. Experimental results showed that toluene adsorption onto ZSM-5 was favourable, following a Langmuir adsorption isotherm model. ZSM-5 zeolite was regenerated using gaseous ozone at low temperature. Adsorbed toluene was oxidised, releasing mainly CO2 and H2O. Traces of oxidation by-products such as acetic acid and acetaldehyde were formed and remained adsorbed after the oxidativate regeneration with ozone. After four successive cycles of adsorption/ozonation, the adsorption efficiency was not affected (92%-99%). These results showed that volatile organic compound (VOC) removal by adsorption onto ZSM-5 zeolite followed by ozone regeneration could be used as a promising hybrid process for the control of VOC emissions in terms of efficiency.

Minimum conditions for the induction of cortical spreading depression in brain slices.

Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma.

Memantine enhances recovery from stroke.

BACKGROUND AND PURPOSE: Stroke treatment is constrained by limited treatment windows and the clinical inefficacy of agents that showed preclinical promise. Yet animal and clinical data suggest considerable poststroke plasticity, which could allow treatment with recovery-modulating agents. Memantine is a well-tolerated N-methyl-D-aspartate glutamate receptor antagonist in common use for Alzheimer disease. METHODS: Memantine, 30 mg/kg per day, or vehicle, was delivered chronically in drinking water beginning >2 hours after photothrombotic stroke. RESULTS: Although there was no difference in infarct size, behavior, or optical intrinsic signal maps in the first 7 days after stroke, mice treated chronically with memantine showed significant improvements in motor control, measured by cylinder test and grid-walking performance, compared with vehicle-treated animals. Optical intrinsic signal revealed an increased area of forepaw sensory maps at 28 days after stroke. There was decreased reactive astrogliosis and increased vascular density around the infarcted cortex. Peri-infarct Western blots revealed increased brain-derived neurotrophic factor and phosphorylated-tropomyosin-related kinase-B receptor expression. CONCLUSIONS: Our results suggest that memantine improves stroke outcomes in an apparently non-neuroprotective manner involving increased brain-derived neurotrophic factor signaling, reduced reactive astrogliosis, and improved vascularization, associated with improved recovery of sensory and motor cortical function. The clinical availability and tolerability of memantine make it an attractive candidate for clinical translation.