Environmental enrichment in combination with Bifidobacterium breve HNXY26M4 intervention amplifies neuroprotective benefits in a mouse model of Alzheimer's disease by modulating glutamine metabolism of the gut microbiome

The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.

Environmental Enrichment and Its Effect on the Welfare of Two Asian Elephants in Africam Safari Wildlife Conservation Park (Puebla, Mexico)

Animal welfare is important in zoos to maintain the physical well-being and psychological health of individuals. An animal is considered to have welfare if it has good nutrition and also expresses its innate behavior, including sensations and feelings experienced as a result of physical health. The objective of this study was to evaluate the effect of environmental enrichment on the behaviors of two Asian elephants in a wildlife conservation park. The behavior of two Asian elephants, a 46-year-old male and a 59-year-old female, was observed. Behavior was measured by quantifying the frequency, latency, and duration of behavioral actions. Measurements were done with ad libitum sampling during 5 days of testing, then observations were recorded with focal sampling for 25 days with environmental enrichment and 25 days without enrichment. Data were analyzed with the Chi-square statistical test using the statistical program SPSS 20, observing significant differences (P the application of environmental enrichment. The frequency of maintenance behaviors was higher when environmental enrichment was provided, and the frequency of social conducts (affiliative and agonistic) decreased. In fact, the behaviors most frequently presented by elephants with and without environmental enrichment were definitely maintenance behaviors. The environmental enrichment program helped to reduce the duration of abnormal behaviors and increase the frequency of typical behaviors of the species. It also increased independent movements within the exhibition area and helped to know each of the elephants individually in order to apply each enrichment combination according to their needs.

Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson’s disease

Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postural instability,as a result of the progressive loss of nigrostriatal dopaminergic neurons.In addition to this neuronal cell loss,Parkinson’s disease is characterized by the accumulation of intracellular protein aggregates,Lewy bodies and Lewy neurites,composed primarily of the proteinα-synuclein.Although it was first described almost 200 years ago,there are no disease-modifying drugs to treat patients with Parkinson’s disease.In addition to conventional therapies,non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders.Among such strategies,environmental enrichment,comprising physical exercise,cognitive stimulus,and social interactions,has been assessed in preclinical models of Parkinson’s disease.Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression,enhancing the expression of neurotrophic factors and modulating neurotransmission.In this review article,we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson’s disease,highlighting its influence on the dopaminergic,cholinergic,glutamatergic and GABAergic systems,as well as the involvement of neurotrophic factors.We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson’s disease,highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.

Environmental enrichment combined with fasudil promotes motor function recovery and axonal regeneration after stroke

Fasudil,a Rho-associated protein kinase(ROCK)inhibitor,has a protective effect on the central nervous system.In addition,environmental enrichment is a promising technique for inducing the recovery of motor impairments in ischemic stroke models.The present study aimed to explore whether environmental enrichment combined with fasudil can facilitate motor function recovery and induce cortical axonal regeneration after stroke.First,a mouse model of ischemic cerebral stroke was established by photochemical embolization of the left sensorimotor cortex.Fasudil solution(10 mg/kg per day)was injected intraperitoneally for 21 days after the photothrombotic stroke.An environmental enrichment intervention was performed on days 7-21 after the photothrombotic stroke.The results revealed that environmental enrichment combined with fasudil improved motor function,increased growth-associated protein 43 expression in the infarcted cerebral cortex,promoted axonal regeneration on the contralateral side,and downregulated ROCK,p-LIM domain kinase(LIMK)1,and p-cofilin expression.The combined intervention was superior to monotherapy.These findings suggest that environmental enrichment combined with fasudil treatment promotes motor recovery after stroke,at least partly by stimulating axonal regeneration.The underlying mechanism might involve ROCK/LIMK1/cofilin pathway regulation.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.20160858A232)on February 24,2016.

Memantine combined with environmental enrichment improves spatial memory and alleviates Alzheimer's disease-like pathology in senescence-accelerated prone-8(SAMP8) mice

Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease (AD). Environmental enrichment (EE) has shown significant beneficial effects on func- tional improvement in AD. In this study, we sought to determine whether combining these two distinct therapies would yield greater benefit than either drug used alone. We investigated the effect of memantine combined with EE on spatial learning and memory and AD-like pathology in a widely used AD model, the senescence-accelerated prone mice (SAMP8). The SAMP8 mice were randomly assigned to enriched housing (EH) or standard housing (SH), where either memantine (20 mg/kg) or saline was given by gastric lavage once daily continuously for eight weeks. Our results showed that, when provided separately, memantine and EE significantly improved spatial learning and memory by shortening escape latencies and increasing the frequency of entrance into the target quadrant. When combined, memantine and EE showed additive effect on learning and memory as evidenced by significant shorter escape latencies and higher frequency of target entrance than either drug alone. Consistent with the behavior results, pathological studies showed that both memantine and EE significantly reduced hippocampal CA1 neurofibrilliary tangles (NFTs) as well as amyloid beta precursor protein (APP) levels. Combining both therapies synergistically lessened NFTs and APP expression compared to either drug alone in SAMP8 mice, indicating that the combination of memantine with EE could offer a novel and efficient therapeutic strategy for the treatment of AD.

Impact of Vertically-Suspended Environmental Enrichment and Two Densities of Fish on Circular Tank Velocity Profiles

Vertically-suspended environmental enrichment has been shown to produce improvements in fish growth during hatchery rearing in circular tanks. This study documented the effects of a novel suspended structure on the velocity profile of a 3.63-m diameter circular tank containing juvenile landlocked fall Chinook salmon (Oncorhynchus tshawytscha) at two different densities (9.0 and 34.3 kg/m3). The addition of vertically-suspended structure to the tank significantly decreased velocities at nearly every sampling point, with velocities typically dropping from 15 cm/s without structure to less than 6 cm/s when structure was present. Fish density also significantly impacted in-tank velocities, with an inverse relationship observed between the density of fish and water velocity. Significant interactions were present among the presence or absence of structure and fish density. When structure and fish were absent, the velocity at the edge of the tank was 15.63 cm/s, which was significantly higher than the 4.75 cm/s velocity when both structure and the lower fish density were added, which was in turn significantly higher than the 2.29 cm/s velocity observed with structure and higher fish density. Despite the potentially unique features of this study, vertically-suspended environmental enrichment and the presence of fish clearly alter circular tank water velocities, which may at least partially explain the improvements in fish rearing performance observed with the use of suspended structure.

Vertically-Suspended Environmental Enrichment Improves Growth of Landlocked Fall Chinook Salmon during Initial Hatchery Rearing

Environmental enrichment has been shown to improve juvenile salmonid growth during hatchery rearing. This study examined the effects of vertically-suspended environmental enrichment starting seven days after feed training and continuing for the next 32 days of landlocked fall Chinook salmon (Oncorhynchus tshawytscha) rearing. At the end of this experiment, final tank weights, gain, percent gain, and feed conversion ratio were all significantly improved in the tanks of salmon with environmental enrichment compared to barren tanks, with a nearly 25% improvement in feed conversion ratio. Individual salmon in tanks with environmental enrichment were significantly longer and weighed significantly more than salmon from tanks without enrichment. Specific growth rate was also significantly improved with the use of enrichment. The use of vertically-suspended environmental enrichment to improve growth and rearing efficiency is recommended during the initial rearing of landlocked fall Chinook salmon.

Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

Neuroprotection and recovery from early-life adversity: considerations for environmental enrichment

In the laboratory,environmental enrichment（EE）is used as a protocol to understand the functional,behavioral and molecular mechanisms that underlie neural plasticity（van Praag et al.,2000;Sale et al.,2014）.In addition,it is utilized to provide supplementary resources to animals in order to maintain their well-being and to preserve the scientific validity of the study at hand（see http：//www.nap.edu/catalog/12910/guide-for-thecare-and-use-of-laboratory-animals-eighth）.

Seniors’ experiences of visual art environmental enrichment

The present study aimed at determining whether short-term exposure to art in shared common areas in congregate housing units could affect health and health determinants among the residents. Ten residents (mean age 80.4 years) at one block were exposed to visual art environmental enrichment in common areas over a period of three months. Thirteen persons (mean age 86.6 years) living in another block played in-house boule. Cornell’s test, Mini-Mental tests (MMT), and face recognition test were performed to assess depression, cognition, and episodic memory, respectively before and after the intervention. The results show that visual art environmental enrichment in common areas and lack of stimulating and guiding dialogues show a change in depression scores in the intervention group (p = 0.018) and the control group (p = 0.009). MMT scores improved only in the control group (p = 0.003). No changes in episodic memory in any of the groups were observed. It could be concluded that in order to obtain a positive result of short term visual art environmental enrichment, guiding art dialogues conducted by nurses, as described in previous research, should be added to visual art environmental enrichment in healthcare settings.

Influence of environmental enrichment on hippocampal synapses in adolescent offspring of mothers exposed to prenatal stress

Environmental enrichment attenuates hippocampal synaptic injury induced by prenatal stress in offspring. However, the influence of hippocampal synaptic changes and regional differences in prenatal stress remains poorly understood. The present study induced stress in Sprague Dawley rats, which were at gestational age 13-19 days. Following weaning, the offspring were raised in an enriched environment to establish models of stress ＋ enriched environment. Dendritic spine density and synaptophysin expression were detected in hippocampal neurons using Golgi staining and western blot analysis, respectively. Results showed that enriched environment increased dendritic spine density of apical dendrites in CA1 pyramidal cells and basal dendrites of granular cells in the outer layer of the dentate gyrus. In addition, hippocampal synaptophysin expression increased and the effects of prenatal stress on neuronal dendritic spines were reversed in adolescence.

Does the provision of live black soldier fly and yellow mealworm larvae improve Muscovy duck welfare?

Background The provision of environmental enrichments to Muscovy ducks could reduce the expression of the aggressive behaviors.The aim of the present study was to evaluate the effects of black soldier fly(BSF)and yellow mealworm(YM)live larva provision on Muscovy duck performance,excreta corticosterone metabolites(ECM),behavior,and blood parameters.Methods A total of 1263-day-old female Muscovy ducklings were allotted to 18 pens(6 replicates/treatment,7 birds/pen)and assigned to 3 experimental treatments:a control group fed commercial feed,and two experimental treatments fed commercial feed plus the 5%(based on the expected daily feed intake,as fed basis)of BSF and YM live larvae(BSF and YM groups,respectively).A two-phase feeding program was applied:starter(from 3 to 31 days of age)and grower-finisher(from 32 to 55 days of age).The live weight,average daily gain,average daily feed intake,and feed conversion ratio were calculated.Larva consumption times were collected,and video recordings were performed during 3 periods(P)each day:the hour before(P1),during(P2),and after(P3)the larva administration.ECM were evaluated at 3,31,and 55-day-old.Finally,the total red and white blood cell counts,serum proteins,lipids,and liver and renal function serum enzymes were evaluated on 12 birds/treatment.Results The experimental treatment did not affect the growth performance of the birds(P>0.05).Larva consumption times were always similar between the two insect species,except at 14–18 days of age,were BSF larvae were consumed faster than YM larvae(P<0.001).The birds showed less walking activity during P2,and preening behavior increased in YM birds during P3.The C birds increased the attack behavior over the weeks(P<0.05).During weeks 1–3 the YM group reduced the attack frequency(P1>P3;P<0.05).Finally,the provision of live BSF and YM larvae significantly reduced the ECM at 55 days of age and the heterophil to lymphocyte ratio(P<0.05).Conclusions Live BSF and YM larva supplementation in Muscovy duck improves duck welfare,without impairing birds'growth performance.

The Social Enrichment and Training of Large Cats and Cheetahs

Environmental enrichment increases the expression of behavior and welfare. The aim of the study was to analyze situation of the social enrichment （training） of big cats and cheetahs in Czech and Slovak zoos based on the evaluation questionnaire. It was found out that social enrichment, as part of the environmental enrichment, was used in 50% of animal, 16 animal get training only. A lot of animal had positive reactions on enrichment.

Effects of odors on behaviors of captive Amur leopards Panthera pardus orientalis

Captive environments often fail to resemble the wild environment in respects of limited space, unchanging habitat, lack of stimulus and contingency. Common animal welfare problems which occur in captive animals include low behavioral diversity, abnormal behavior and excessive inactivity. Environmental enrichment, as an effective strategy to tackle these problems and promote mental health of captive animals, has been recognized as an important principal for captive animal management. Among all the enriehment techniques, olfactory enrichment is a simple and effective method for improving the well-being of the olfactory sensitive felids. Behavioral problems were observed in six Amur leopards Panthera pardus orientalis at Beijing Zoological Garden. These were held in the older type exhibits which have now been rebuilt. These behaviors include stereotypic behavior and excessive inactivity caused by the spatially limited enclosures with low levels of stimuli. To determine the effects of predator, prey, and herb odors as potential enrichment materials for captive leopards, we conducted olfactory enrichment experiments for the leopards and tested the effects of nutmeg Myristica fragrans, feces of roe deer Capreolus capreolus and urine of Amur tiger Panthera tigris altaica to test for an increase in behavioral repertoire and activity. Odors provided in this study were also believed to improve the psychological and physiological health of individuals. To standardize the method of presentation the odors were introduced to the enclosures by rubbing or spraying onto a clean towel. Our results show that the selected three odors effectively increased the behavioral diversity. Ten new behavior types were observed in the nutmeg experiment, eight in the feces of roe deer experiment and six in the tiger urine experiment. Among the three odors, cats responded to nutmeg for the longest duration, followed by tiger urine and feces of roe deer. Leopards showed more play behavior in presence of nutmeg while more investigatory behavior in presences of feces of roe deer and tiger urine. Providing novel odors increased the spatial use of the exhibit and the animal＇ s increased use of the logs, sleeping platforms and bars in the cages. Novel odors also significantly increased the overall activity of the leopards, but the effects were diminished in about three hours.

Color of Vertically-Suspended Structure Does Not Impact the Growth of Rainbow Trout Reared in Circular Tanks

This study examined the effects of five different colors of vertically-suspended environmental enrichment on the growth of juvenile Shasta strain rainbow trout (Oncorhynchus mykiss) during hatchery rearing in circular tanks. The colors used were silver (unpainted aluminum—control), safety red, semi-gloss black, hunter green, and safety blue. After 86 days, total tank weight, weight gain, and feed conversion ration were not significantly different among any of the color treatments. Individual fish weights, lengths, and condition factors were also not significantly different among the treatments. The results of this study indicate that the relatively small amount of color present on the suspended structure did not affect rainbow trout growth. Thus, the inherent silver color of the aluminum angles does not need to be changed.

Effect of differential rearing environments on nicotine-stimulated locomotor activity and nicotinic acetylcholine receptor subtypes

OBJECTIVE Individuals vary in sensitivity to the behavioral effects of nicotine,resulting in differences in their vulnerability to addiction.The role of rearing environment in determining individual sensitivity to nicotine is unclear.The neuropharmacological mechanisms mediating the effect of rearing environment on the actions of nicotine are also understood.Thus,the contribution of rearing environment in determining the sensitivity to the locomotor effects of nicotine and regulating α4β2*-and α7-nicotinic acetylcholine(n ACh) receptor expressionwas determined in rats reared in isolated(IC) or enriched(EC) conditions.METHODS To measure locomotor activity,adolescent rats(postnatal day 21-51)were injected with saline(1 mL·kg^(-1)) or nicotine(0.3 mg·kg^(-1)) subcutaneously,then placed in chamberswhere ambulatory activity was monitored for 30-min by computer for 14 daily sessions.α4β2*-andα7-n ACh receptor expression in the mesolimbic dopamine pathway was determined by quantitative autoradiography of [125 I]-epibatidine and [125 I]-bungarotoxinbinding,respectively,in 16 μmol·L^(-1) coronal sections.Values for receptor expression in fmol are ±s of 8 brains and compared by two-tailed,unpaired t-test with P<0.05 considered significant.RESULTS EC-rats are similarly sensitive as IC-rats to the locomotor effects of nicotine.[125 I]-epibatidine binding in the ventral tegmental area of EC-rats was reduced(2.8±0.3 fmo L) compared to IC-rats(4.0±0.4 fmo L);there was no difference in the nucleus accumbens.There was no difference between EC-and IC-rats in α7-n ACh receptor expression in the mesolimbic dopamine pathway.CONCLUSION Rearing environment differentially regulates n ACh receptor subtypes in EC and IC rats.These data suggest regulation of n ACh receptors by environmental factors may be a mechanism for the protective effect of enrichment against altered sensitivity to nicotine in genetically vulnerable individuals.The characterization of these mechanisms will aid in development of novel pharmacological tools mimicking the protection afforded by environmental enrichment in nicotine-sensitive individuals.

Frequency of Occupation with Different Objects by Growing Rabbits under Various Conditions

The investigation was carried out with altogether 332 growing rabbits （ZIKA） in six rounds of 8 weeks duration respectively （R1-R6） with the following occupational objects： wooden gnawing stick （WGS）, plastic gnawing stick （PGS） and two iron chains connected by a horizontal stick （ICS）, wooden gnawing limb （WGL） and a horizontal iron chain （HIC）. The feeding system varied from pellet feeding ad libitum （in the first rounds, in the following rounds it decreased pro-rata whereas the proportion of the crude fibre feed （loose or pressed in blocks） increased appropriately） to crude fibre feeding ad libitum. The behavior ＂occupation with the tool＂ was infrared video recorded and continuously analyzed and summarized in hour-values per rabbit. The average frequency of occupation per rabbit and hour ranged from 0,13 to 2.19 concerning the rounds and between 0.12 and 1,30 concerning the tools. Altogether, it could be assumed that different occupational tools had an influence on the engaging behavior but the effect of the round which was affected by the feeding system was higher. The investigation showed that rabbits spent less time occupying with the tool when they were fed with an increasing percentage of crude fibre （less pellets） in the ration.

Exercise and Structure Improve Juvenile Chinook Salmon Rearing Performance

This experiment evaluated the use of an exercise routine and vertically-sus-pended structure during juvenile landlocked fall Chinook salmon (Oncorhynchus tshawytscha; mean ± SE, initial weight 1.47 ± 0.03 g, total length 56.4 ± 0.4 mm) rearing. Four treatments were used: 1) no exercise routine nor vertically-suspended structure, 2) exercise and structure, 3) exercise and no structure, and 4) no exercise and structure. Water velocities in tanks without exercise were 12 cm/s, where-as the exercise routine consisted of seven days at 12 cm/s followed by seven days at 18 cm/s. The structure was an array consisting of four vertically-suspended aluminum angles. Total tank gain and percent gain were significantly greater after 50 days in the tanks of salmon subjected to the exercise routine and structure compared to the three other treatments. Gain and percent gain were also significantly greater in the tanks receiving structure without exercise compared to tanks with exercise and no structure or tanks with neither exercise nor structure. Feed conversion ratio was significantly improved in the salmon tanks with structure and without exercise compared to all other treatments. There were no significant differences for individual fish weight, total length, specific growth rate, or condition factor among any of the treatments at the end of the experiment. These results indicate that the use of both an exercise routine and vertically-suspended structure may be beneficial during the rearing of juvenile landlocked fall Chinook salmon.

Mechanisms of neuroplasticity and brain degeneration: strategies for protection during the aging process

Aging is a dynamic and progressive process that begins at conception and continues until death.This process leads to a decrease in homeostasis and morphological,biochemical and psychological changes,increasing the individual’s vulnerability to various diseases.The growth in the number of aging populations has increased the prevalence of chronic degenerative diseases,impairment of the central nervous system and dementias,such as Alzheimer’s disease,whose main risk factor is age,leading to an increase of the number of individuals who need daily support for life activities.Some theories about aging suggest it is caused by an increase of cellular senescence and reactive oxygen species,which leads to inflammation,oxidation,cell membrane damage and consequently neuronal death.Also,mitochondrial mutations,which are generated throughout the aging process,can lead to changes in energy production,deficiencies in electron transport and apoptosis induction that can result in decreased function.Additionally,increasing cellular senescence and the release of proinflammatory cytokines can cause irreversible damage to neuronal cells.Recent reports point to the importance of changing lifestyle by increasing physical exercise,improving nutrition and environmental enrichment to activate neuroprotective defense mechanisms.Therefore,this review aims to address the latest information about the different mechanisms related to neuroplasticity and neuronal death and to provide strategies that can improve neuroprotection and decrease the neurodegeneration caused by aging and environmental stressors.

An enriched environment increases the expression of fibronectin type Ⅲ domain-containing protein 5 and brain-derived neurotrophic factor in the cerebral cortex of the ischemic mouse brain

Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.