{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T09:20:19Z","timestamp":1768641619178,"version":"3.49.0"},"reference-count":87,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T00:00:00Z","timestamp":1384300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in  ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.<\/jats:p>","DOI":"10.3390\/ijms141122258","type":"journal-article","created":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T12:55:52Z","timestamp":1384347352000},"page":"22258-22273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Peter","family":"Kiss","sequence":"first","affiliation":[{"name":"Department of Anatomy, PTE-MTA \"Lendulet\" PACAP Research Team, University of Pecs,  Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyongyver","family":"Vadasz","sequence":"additional","affiliation":[{"name":"Department of Anatomy, PTE-MTA \"Lendulet\" PACAP Research Team, University of Pecs,  Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanka","family":"Kiss-Illes","sequence":"additional","affiliation":[{"name":"Department of Anatomy, PTE-MTA \"Lendulet\" PACAP Research Team, University of Pecs,  Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Anatomy, PTE-MTA \"Lendulet\" PACAP Research Team, University of Pecs,  Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Tamas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, PTE-MTA \"Lendulet\" PACAP Research Team, University of Pecs,  Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora","family":"Reglodi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, PTE-MTA \"Lendulet\" PACAP Research Team, University of Pecs,  Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miklos","family":"Koppan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Pecs, Pecs 7624, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1467-7687.2006.00499.x","article-title":"Brain and cognitive-behavioural development after asphyxia at term birth","volume":"9","author":"Wyatt","year":"2006","journal-title":"Dev. Sci"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1002\/jnr.21715","article-title":"Plasticity of hippocampus following perinatal asphyxia: Effects on postnatal apoptosis and neurogenesis","volume":"86","author":"Morales","year":"2008","journal-title":"J. Neurosci. Res"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1055\/s-2000-9293","article-title":"Hypoxic-ischmic encephalopathy","volume":"17","author":"Vannucci","year":"2000","journal-title":"Am. J. Perinatol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s12640-010-9208-9","article-title":"Perinatal asphyxia: Current status and approaches towards neuroprotective strategies, with focus on sentinel proteins","volume":"19","author":"Morales","year":"2011","journal-title":"Neurotox. Res"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/archneur.1976.00500100030012","article-title":"Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study","volume":"33","author":"Sarnat","year":"1976","journal-title":"Arch. Neurol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.pcl.2004.01.016","article-title":"Low Apgar scores and the definition of birth asphyxia","volume":"51","author":"Leuthner","year":"2004","journal-title":"Pediatr. Clin. North. Am"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.neuroscience.2007.06.060","article-title":"Failure to complete apoptosis following neonatal hypoxia-ischemia manifests as \u201ccontinuum\u201d phenotype of cell death and occurs with multiple manifestations of mitochondrial dysfunction in rodent forebrain","volume":"149","author":"Northington","year":"2007","journal-title":"Neuroscience"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1177\/0883073809338212","article-title":"Apoptotic mechanisms in the immature brain: Involvement of mitochondria","volume":"24","author":"Hagberg","year":"2009","journal-title":"J. Child Neurol"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.2353\/ajpath.2009.090463","article-title":"Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms","volume":"175","author":"Ginet","year":"2009","journal-title":"Am. J. Pathol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/cdd.2009.33","article-title":"Life and death partners: Apoptosis, autophagy and the cross-talk between them","volume":"16","author":"Bialik","year":"2009","journal-title":"Cell. Death Differ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.pbb.2011.03.016","article-title":"Glutamate signaling in the pathophysiology and therapy of prenatal insults","volume":"100","author":"Holopainen","year":"2012","journal-title":"Pharmacol. Biochem. Behav"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0304-3940(96)13293-6","article-title":"Perinatal asphyxia-induced changes in rat brain tyrosine hydroxylase-immunoreactive cell body number: Effects of nicotine treatment","volume":"221","author":"Chen","year":"1997","journal-title":"Neurosci. Lett"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0887-8994(92)90050-9","article-title":"Excitatory amino acids in cerebrospinal fluid in neonatal asphyxia","volume":"8","author":"Riikonen","year":"1992","journal-title":"Pediatr. Neurol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/j.1651-2227.1993.tb12601.x","article-title":"Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: Relationship to hypoxic-ischemic encephalopathy","volume":"82","author":"Hagberg","year":"1993","journal-title":"Acta Paediatr"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.nurt.2009.10.016","article-title":"Review Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury","volume":"7","author":"Ziebell","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jneuroim.2007.07.023","article-title":"Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia","volume":"190","author":"Lehnardt","year":"2007","journal-title":"J. Neuroimmunol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.cell.2010.02.016","article-title":"Mechanisms underlying inflammation in neurodegeneration","volume":"140","author":"Glass","year":"2010","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1172\/JCI30555","article-title":"Physiology and immunology of the cholinergic antiinflammatory pathway","volume":"117","author":"Tracey","year":"2007","journal-title":"J. Clin. Invest"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0887-8994(93)90006-X","article-title":"Nature, time-course, and extent of cerebral edema in perinatal hypoxic-ischemic brain damage","volume":"9","author":"Vannucci","year":"1993","journal-title":"Pediatr. Neurol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12640-012-9310-2","article-title":"Further studies on the hypothesis of PARP-1 inhibition as a strategy for lessening the long-term effects produced by perinatal asphyxia: Effects of nicotinamide and theophylline on PARP-1 activity in brain and peripheral tissue: Nicotinamide and theophylline on PARP-1 activity","volume":"22","author":"Bustamante","year":"2012","journal-title":"Neurotox. Res"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ujhazy, E., Dubovicky, M., Navarova, J., Sedlackova, N., Danihel, L., Brucknerova, I., and Mach, M. (2013). Subchronic perinatal asphyxia in rats: Embryo-foetal assessment of a new model of oxidative stress during critical period of development. Food Chem. Toxicol, in press.","DOI":"10.1016\/j.fct.2013.07.023"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF03033903","article-title":"Perinatal asphyxia induces neurogenesis in hippocampus: An organotypic study","volume":"12","author":"Morales","year":"2007","journal-title":"Neurotox. Res"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.brainres.2011.01.081","article-title":"A clinically relevant model of perinatal global ischemic brain damage in rats","volume":"1383","author":"Yang","year":"2011","journal-title":"Brain Res"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0166-4328(03)00146-3","article-title":"Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy","volume":"145","author":"Ten","year":"2003","journal-title":"Behav. Brain Res"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.bbr.2004.06.019","article-title":"Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic\/ischemic injury","volume":"157","author":"Lubics","year":"2005","journal-title":"Behav. Brain Res"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/BF03033977","article-title":"Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate","volume":"8","author":"Kiss","year":"2005","journal-title":"Neurotox. Res"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF03033917","article-title":"Changes in open-field activity and novelty-seeking behavior in periadolescent rats neonatally treated with monosodium glutamate","volume":"12","author":"Kiss","year":"2007","journal-title":"Neurotox. Res"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.brainres.2008.12.018","article-title":"Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats","volume":"1255","author":"Kiss","year":"2009","journal-title":"Brain Res"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.brainresbull.2010.10.003","article-title":"Changes in neostriatal and hippocampal synaptic densities in perinatal asphyctic male and female young rats: Role of hypothermia","volume":"84","author":"Cebral","year":"2011","journal-title":"Brain Res. Bull"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00221-009-2103-z","article-title":"Nicotinamide prevents the long-term effects of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats","volume":"202","author":"Morales","year":"2010","journal-title":"Exp. Brain Res"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-2094-10-14","article-title":"Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats","volume":"10","author":"Vlassaks","year":"2013","journal-title":"J. Neuroinflammation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000089951","article-title":"Erythropoietin downregulates bax and DP5 proapoptotic gene expression in neonatal hypoxic-ischemic brain injury","volume":"89","author":"Kumral","year":"2006","journal-title":"Biol. Neonate"},{"key":"ref_33","first-page":"771","article-title":"Histological study of the protective effect of melatonin on neural cells after neonatal hypoxia-ischemia","volume":"27","author":"Alvarez","year":"2012","journal-title":"Histol. Histopathol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.neuint.2009.03.010","article-title":"Neuroprotection by co-treatment and post-treating with calcitriol following the ischemic and excitotoxic insult in vivo and in vitro","volume":"55","author":"Kajta","year":"2009","journal-title":"Neurochem. Int."},{"key":"ref_35","first-page":"306","article-title":"The effects of early experience on problem solving at maturity","volume":"2","author":"Hebb","year":"1947","journal-title":"Am. Psychol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nrn1970","article-title":"Enriched environments, experience-dependent plasticity and disorders of the nervous system","volume":"7","author":"Nithianantharajah","year":"2006","journal-title":"Nat. Rev. Neurosci"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.brainres.2009.01.004","article-title":"Early postnatal enriched environment decreases retinal degeneration induced by monosodium glutamate treatment","volume":"1259","author":"Szabadfi","year":"2009","journal-title":"Brain Res"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16111","DOI":"10.3390\/ijms140816111","article-title":"Gender-dependent effects of enriched environment and social isolation in ischemic retinal lesion in adult rats","volume":"14","author":"Kiss","year":"2013","journal-title":"Int. J. Mol. Sci"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"19054","DOI":"10.3390\/ijms140919054","article-title":"Exposure to enriched environment decreases neurobehavioral deficits induced by neonatal glutamate toxicity","volume":"14","author":"Horvath","year":"2013","journal-title":"Int. J. Mol. Sci"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.brainresbull.2008.12.011","article-title":"Effects of maternal separation on the neurobehavioral development of newborn Wistar rats","volume":"79","author":"Farkas","year":"2009","journal-title":"Brain Res. Bull"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s10571-009-9492-1","article-title":"Effects of acute perinatal asphyxia in the rat hippocampus","volume":"30","author":"Frizzo","year":"2010","journal-title":"Cell. Mol. Neurobiol"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11011-012-9367-x","article-title":"Metabolic effects of perinatal asphyxia in the rat cerebral cortex","volume":"28","author":"Souza","year":"2013","journal-title":"Metab. Brain Dis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s00221-006-0679-0","article-title":"Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth","volume":"177","author":"Bustamante","year":"2007","journal-title":"Exp. Brain Res"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/PL00005670","article-title":"Delayed neuronal death following perinatal asphyxia in rat","volume":"115","author":"Chen","year":"1997","journal-title":"Exp. Brain Res"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.neuroscience.2010.09.024","article-title":"Triggered by asphyxia neurogenesis seems not to be an endogenous repair mechanism, gliogenesis more like it","volume":"171","author":"Keilhoff","year":"2010","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.expneurol.2009.06.007","article-title":"Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia","volume":"219","author":"Capani","year":"2009","journal-title":"Exp. Neurol"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1159\/000346685","article-title":"Cerebral and hepatic inflammatory response after neonatal hypoxia-ischemia in newborn rats","volume":"35","author":"Bonestroo","year":"2013","journal-title":"Dev. Neurosci"},{"key":"ref_48","first-page":"177","article-title":"Proinflammatory cytokines in injured rat brain following perinatal asphyxia","volume":"40","author":"Kalisze","year":"2002","journal-title":"Folia Neuropathol"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00221-006-0842-7","article-title":"Plasticity of basal ganglia neurocircuitries following perinatal asphyxia: Effect of nicotinamide","volume":"180","author":"Klawitter","year":"2007","journal-title":"Exp. Brain Res"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1006\/exnr.2001.7855","article-title":"Perinatal asphyxia induced neuronal loss by apoptosis in the neonatal rat striatum: A combined TUNEL and stereological study","volume":"174","author":"Schmitz","year":"2002","journal-title":"Exp. Neurol"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e15326","DOI":"10.1371\/journal.pone.0015326","article-title":"Perinatal asphyxia affects rat auditory processing: Implications for auditory perceptual impairments in neurodevelopmental disorders","volume":"5","author":"Strata","year":"2010","journal-title":"PLoS One"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10809","DOI":"10.1523\/JNEUROSCI.1857-09.2009","article-title":"Setting the pace for retinal development: Environmental enrichment acts through insulin-like growth factor 1 and brain-derived neurotrophic factor","volume":"29","author":"Landi","year":"2009","journal-title":"J. Neurosci"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00702-010-0496-2","article-title":"Combination of intracortically administered VEGF and environmental enrichment enhances brain protection in developing rats","volume":"118","author":"Ortuzar","year":"2011","journal-title":"J. Neural Transm"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Reynolds, S., Urruela, M., and Devine, D.P. (2013). Effects of environmental enrichment on repetitive behaviors in the BTBR T + tf\/J mouse model of autism. Autism Res.","DOI":"10.1002\/aur.1298"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1023\/A:1021413200461","article-title":"Neonatal handling and environmental enrichment effects on emotionality, novelty\/reward seeking, and age-related cognitive and hippocampal impairments: Focus on the Roman rat lines","volume":"27","author":"Escorihuela","year":"1997","journal-title":"Behav. Genet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bbr.2013.06.021","article-title":"Environmental enrichment ameliorates depressive-like symptoms in young rats bred for learned helplessness","volume":"252","author":"Richter","year":"2013","journal-title":"Behav. Brain Res"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.bbr.2013.05.041","article-title":"Environmental enrichment effects on the neurobehavioral profile of selective outbred trait anxiety rats","volume":"252","author":"Ravenelle","year":"2013","journal-title":"Behav. Brain Res"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s10071-012-0583-x","article-title":"Environmental enrichment affects suboptimal, risky, gambling-like choice by pigeons","volume":"16","author":"Pattison","year":"2013","journal-title":"Anim. Cogn"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0006-8993(00)03249-2","article-title":"Enriched environment during development is protective against lead-induced neurotoxicity","volume":"896","author":"Schneider","year":"2001","journal-title":"Brain Res"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Johnson, E.M., Traver, K.L., Hoffman, S.W., Harrison, C.R., and Herman, J.P. (2013). Environmental enrichment protects against functional deficits caused by traumatic brain injury. Front. Behav. Neurosci.","DOI":"10.21236\/ADA584995"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/dev.420250304","article-title":"Neonatal 6-OHDA lesions and rearing in complex environments: Regional effects on adult brain 14C-2-deoxyglucose uptake revealed by exposure to novel stimulation","volume":"25","author":"Nobrega","year":"1992","journal-title":"Dev. Psychobiol"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.expneurol.2013.01.007","article-title":"Environmental enrichment promotes robust functional and histological benefits in female rats after controlled cortical impact injury","volume":"247","author":"Monaco","year":"2013","journal-title":"Exp. Neurol"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.expneurol.2012.11.026","article-title":"Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat","volume":"241","author":"Rojas","year":"2013","journal-title":"Exp. Neurol"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbr.2007.07.039","article-title":"Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats","volume":"186","author":"Imanaka","year":"2008","journal-title":"Behav. Brain Res"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.neuroscience.2013.01.036","article-title":"Visual depth perception in normal and deprived rats: Effects of environmental enrichment","volume":"236","author":"Baroncelli","year":"2013","journal-title":"Neuroscience"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.neulet.2010.10.065","article-title":"Comparison between PACAP- and enriched environment-induced retinal protection in MSG-treated newborn rats","volume":"487","author":"Kiss","year":"2011","journal-title":"Neurosci. Lett"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/dev.20253","article-title":"Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions","volume":"50","author":"Comeau","year":"2008","journal-title":"Dev. Psychobiol"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.neubiorev.2006.06.019","article-title":"Postnatal environmental or experiential amelioration of neurobehavioral effects of perinatal alcohol exposure in rats","volume":"31","author":"Hannigan","year":"2007","journal-title":"Neurosci. Biobehav. Rev"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.bbr.2006.06.012","article-title":"Importance of early environment in the development of post-traumatic stress disorder-like behaviors","volume":"173","author":"Imanaka","year":"2006","journal-title":"Behav. Brain Res"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.nlm.2006.07.003","article-title":"Effects of daily environmental enrichment on memory deficits and brain injury following neonatal hypoxia-ischemia in the rat","volume":"87","author":"Pereira","year":"2007","journal-title":"Neurobiol. Learn. Mem"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00213-005-0223-0","article-title":"Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: Modulatory effects of an enriched environment","volume":"184","author":"Adriani","year":"2006","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.expneurol.2009.04.030","article-title":"Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury","volume":"218","author":"Robertson","year":"2009","journal-title":"Exp. Neurol"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ijdevneu.2007.11.005","article-title":"Neuroprotection of brain-derived neurotrophic factor against hypoxic injury in vitro requires activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase","volume":"26","author":"Sun","year":"2008","journal-title":"Int. J. Dev. Neurosci"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yu, K., Wu, Y., Jia, J., Hu, Y., Zhang, Q., Xie, H., Liu, G., Chen, Y., and Guo, Z. (2013). Neuroprotective effects of prior exposure to enriched environment on cerebral ischemia\/reperfusion injury in rats: The possible molecular mechanism. Brain Res, in press.","DOI":"10.1016\/j.brainres.2013.09.036"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11715","DOI":"10.1523\/JNEUROSCI.3541-12.2013","article-title":"Enriched early life experiences reduce adult anxiety-like behavior in rats: A role for insulin-like growth factor 1","volume":"33","author":"Baldini","year":"2013","journal-title":"J. Neurosci"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.bbr.2012.12.047","article-title":"The effects of enriched environment on BDNF expression in the mouse cerebellum depending on the length of exposure","volume":"243","author":"Toledo","year":"2013","journal-title":"Behav. Brain Res"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0169-328X(94)90246-1","article-title":"Glucocorticoid receptor and NGFI-A gene expression are induced in the hippocampus after environmental enrichment in adult rats","volume":"23","author":"Olsson","year":"1994","journal-title":"Brain Res. Mol. Brain Res"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.neuron.2011.12.020","article-title":"Motor protein KIF1A is essential for hippocampal synaptogenesis and learning enhancement in an enriched environment","volume":"73","author":"Kondo","year":"2012","journal-title":"Neuron"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/syn.20086","article-title":"Effect of neonatal isolation on the noradrenergic transduction system in the rat hippocampal slice","volume":"54","author":"Kusaka","year":"2004","journal-title":"Synapse"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/J006v23n01_04","article-title":"Behavioral responses to tactile stimuli in children with cerebral palsy","volume":"23","author":"Clayton","year":"2003","journal-title":"Phys. Occup. Ther. Pediatr"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00221-007-1186-7","article-title":"Acute perinatal asphyxia impairs non-spatial memory and alters motor coordination in adult male rats","volume":"185","author":"Simola","year":"2008","journal-title":"Exp. Brain Res"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/0003-3472(75)90114-1","article-title":"Postnatal development of locomotion in the laboratory rat","volume":"23","author":"Altman","year":"1975","journal-title":"Anim. Behav"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0165-3806(00)00044-4","article-title":"Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity","volume":"121","author":"Dam","year":"2000","journal-title":"Dev. Brain Res"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0196-9781(91)90186-S","article-title":"Vasoactive intestinal peptide antagonist retards the development of neonatal behaviors in the rat","volume":"12","author":"Hill","year":"1991","journal-title":"Peptides"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0166-4328(02)00289-9","article-title":"The effects of PACAP and PACAP antagonist on the neurobehavioral development of newborn rats","volume":"140","author":"Reglodi","year":"2003","journal-title":"Behav. Brain Res"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0006-8993(71)90526-9","article-title":"Vulnerability of developing brain. II. Effects of early nutritional deprivation on reflex ontogeny and development on behavior in the rat","volume":"28","author":"Smart","year":"1971","journal-title":"Brain Res"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0006-8993(71)90105-3","article-title":"Vulnerability of developing brain. VI. Relative effects of foetal and early postnatal undernutrition on reflex ontogeny and development of behavior in the rat","volume":"33","author":"Smart","year":"1971","journal-title":"Brain Res"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/11\/22258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:34Z","timestamp":1760219434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/11\/22258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,13]]},"references-count":87,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11]]}},"alternative-id":["ijms141122258"],"URL":"https:\/\/doi.org\/10.3390\/ijms141122258","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,13]]}}}