Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A2A receptors (A2ARs) have been considered as key elements in signaling pathways mediating neurodegenerative diseases such as Huntington's and Alzheimer's, as well as cognitive function regulation. Herein, we investigated A2AR role in cognitive impairment induced by chronic intermittent hypoxia (CIH). Mice were exposed to CIH 7 h every day for 4 weeks, and intraperitoneally injected with A2AR agonist CGS21680 or A2AR antagonist SCH58261 half an hour before IH exposure daily. The 8-arm radial arm maze was utilized to assess spatial memory after CIH exposures.To validate findings using pharmacology, the impact of intermittent hypoxia was investigated in A2AR knockout mice. CIH-induced memory dysfunction was manifested by increased error rates in the radial arm maze test. The behavioral changes were associated with hippocampal pathology, neuronal apoptosis, and synaptic plasticity impairment. The stimulation of adenosine A2AR exacerbated memory impairment with more serious neuropathological damage, attenuated long-term potentiation (LTP), syntaxin down-regulation, and increased BDNF protein. Moreover, apoptosis-promoting protein cleaved caspase-3 was upregulated while anti-apoptotic protein Bcl-2 was downregulated. Consistent with these findings, A2AR inhibition with SCH58261 and A2AR deletion exhibited the opposite result. Overall, these findings suggest that A2AR plays a critical role in CIH-induced impairment of learning and memory by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity. Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice.

Impact of neonatal anoxia and hypothermic treatment on development and memory of rats.

Therapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood. These effects seem to be reduced by post-insult hypothermia. Epigenetic-related mechanisms have been postulated as valuable tools for developing new therapies. Dentate gyrus neurogenesis is regulated by epigenetic factors. This study evaluated whether TH effects in a rodent model of preterm oxygen deprivation are based on epigenetic alterations. The effects of TH on both developmental features (somatic growth, maturation of physical characteristics and early neurological reflexes) and performance of behavioral tasks at adulthood (spatial reference and working memory, and fear conditioning) were investigated in association with the possible involvement of the epigenetic operator Enhancer of zeste homolog 2 (Ezh2), possibly related to long-lasting effects on hippocampal neurogenesis. Results showed that TH reduced both anoxia-induced hippocampal neurodegeneration and anoxia-induced impairments on risk assessment behavior, acquisition of spatial memory, and extinction of auditory and contextual fear conditioning. In contrast, TH did not prevent developmental alterations caused by neonatal anoxia and did not restore hippocampal neurogenesis or cause changes in EZH2 levels. In conclusion, despite the beneficial effects of TH in hippocampal neurodegeneration and in reversing disruption of performance of behavioral tasks following oxygen deprivation in prematurity, these effects seem not related to developmental alterations and hippocampal neurogenesis and, apparently, is not caused by Ezh2-mediated epigenetic alteration.

Cerebral Hypoxia: Its Role in Age-Related Chronic and Acute Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD) has been reported with widely varying frequency but appears to be strongly associated with aging. Outside of the surgical arena, chronic and acute cerebral hypoxia may exist as a result of respiratory, cardiovascular, or anemic conditions. Hypoxia has been extensively implicated in cognitive impairment. Furthermore, disease states associated with hypoxia both accompany and progress with aging. Perioperative cerebral hypoxia is likely underdiagnosed, and its contribution to POCD is underappreciated. Herein, we discuss the various disease processes and forms in which hypoxia may contribute to POCD. Furthermore, we outline hypoxia-related mechanisms, such as hypoxia-inducible factor activation, cerebral ischemia, cerebrovascular reserve, excitotoxicity, and neuroinflammation, which may contribute to cognitive impairment and how these mechanisms interact with aging. Finally, we discuss opportunities to prevent and manage POCD related to hypoxia.

Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce 'Brain Fog' and Results in Behavioral Changes that Favor Viral Survival.

Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.

Reversal of neurovascular coupling in the default mode network: Evidence from hypoxia.

Local changes in cerebral blood flow are thought to match changes in neuronal activity, a phenomenon termed neurovascular coupling. Hypoxia increases global resting cerebral blood flow, but regional cerebral blood flow (rCBF) changes are non-uniform. Hypoxia decreases baseline rCBF to the default mode network (DMN), which could reflect either decreased neuronal activity or altered neurovascular coupling. To distinguish between these hypotheses, we characterized the effects of hypoxia on baseline rCBF, task performance, and the hemodynamic (BOLD) response to task activity. During hypoxia, baseline CBF increased across most of the brain, but decreased in DMN regions. Performance on memory recall and motion detection tasks was not diminished, suggesting task-relevant neuronal activity was unaffected. Hypoxia reversed both positive and negative task-evoked BOLD responses in the DMN, suggesting hypoxia reverses neurovascular coupling in the DMN of healthy adults. The reversal of the BOLD response was specific to the DMN. Hypoxia produced modest increases in activations in the visual attention network (VAN) during the motion detection task, and had no effect on activations in the visual cortex during visual stimulation. This regional specificity may be particularly pertinent to clinical populations characterized by hypoxemia and may enhance understanding of regional specificity in neurodegenerative disease pathology.

Neurocognitive outcomes in adults following cerebral hypoxia: A systematic literature review.

BACKGROUND: Hypoxic ischemic brain injury (HIBI) occurs as a result of complete or partial disruption of cerebral oxygen supply. The physical and cognitive sequelae of adults following hypoxia varies widely. OBJECTIVE: To systematically review studies exploring the neuropsychological outcomes following hypoxic brain insult in adults. METHODS: Data was sourced using six databases (CINAHL, Cochrane, Embase, Medline, PsycInfo and Web of Science). Initial MESH terms identified 2,962 articles. After a three-stage independent review process, 18 articles, 9 case studies and 9 group studies were available for data synthesis from 1990-2012. Case study data was converted to standardised scores and compared to available test norms. Cohen's d was calculated to permit group data interpretation. RESULTS: Intellectual decrement was observed in some studies although difficult to delineate given the lack of use of measures of premorbid ability. Cognitive sequelae varied albeit with predominant disturbance in verbal memory, learning ability and executive function observed across studies. Wechsler Memory Scale Revised (WMS-R) visual memory was comparable to normative data. Impaired Rey Osterrieth Complex Figure (ROCFT) performance was found among group studies. Across visuo-constructional and attention domains, performance varied, although no significant difference relative to reported means was observed. CONCLUSIONS: Future studies should consider the use of standardised assessment protocols, which include measures of premorbid functioning and performance validity.

Exosomal shuttled miR-424-5p from ischemic preconditioned microglia mediates cerebral endothelial cell injury through negatively regulation of FGF2/STAT3 pathway.

Exosomes secreted by microglia have been found to play a role in neurovascular unit injury under the ischemic/hypoxic state. However, the modulatory effect of exosomes shuttled miRNAs produced by microglia in endothelial cells remains undefined. Here, an oxygen-glucose deprivation (OGD) model was constructed both in microglia and brain microvascular endothelial cells (BMEC). The exosomes secreted by microglia were isolated, and the exosomal miRNA profile was detected. Next, gain- and loss- functions of miR-424-5p, one of the most differentially expressed miRNAs in microglia derived exosomes, were conducted in BMEC. The results demonstrated that exosomes from OGD-activated microglia aggravated OGD induced BMEC viability and integrity damage as well as the loss of vascular formation. While the damaging effects were markedly attenuated by inhibiting miR-424-5p. In addition, miR-424-5p overexpression significantly aggravated OGD induced BMEC damage and permeability. Mechanistically, bioinformatics analysis indicated that miR-424-5p targeted the FGF2 mediated STAT3 signaling pathway, which was verified via dual luciferase activity assay and RIP experiment. Furthermore, in vivo experiments in the middle cerebral artery occlusion (MCAO) model mice were conducted. The results revealed that inhibition of miR-424-5p markedly reduced neurological dysfunctions and endothelial cell injury induced by MCAO. The above results confirmed that exosomes from OGD activated microglia induced significant cell damage and permeability of BMEC, in which the upregulated miR-424-5p in the exosomes functioned by regulating FGF2/STAT3 pathway.

Forced person-following: a new type of stimulus-bound behavior.

We report a new type of stimulus-bound behavior, denoted forced person-following, which we documented for a patient with hypoxic encephalopathy following a suicide attempt with carbon monoxide poisoning. The patient's brain was damaged in the bilateral frontal, parietal, and temporal lobes and in the basal ganglia. The patient was compelled to follow any person who came into his sight and would continue to do so until the person went out of his sight. The patient also exhibited certain primitive reflexes. The forced person-following exhibited by our patient appears to be a consequence of stimulus-bound behavior due to frontal lobe dysfunction and, to a lesser degree, severe cognitive dysfunctions, e.g., visuospatial deficits, which are related to damage in posterior cortices. The unique behavior exhibited by this patient might contribute to our understanding of innate human behavior.

Ethical Dilemmas in Neonatology - Four Theoretical Cases and Three Monotheistic Approaches: A Pilot Study.

BACKGROUND: Israel's population is diverse, with people of different religions, many of whom seek spiritual guidance during ethical dilemmas. It is paramount for healthcare providers to be familiar with different religious approaches. OBJECTIVES: To describe the attitudes of the three major monotheistic religions when encountering four complex neonatal situations. METHODS: A questionnaire related to four simulated cases was presented to each participant: a non-viable extremely premature infant (case 1), a severely asphyxiated term infant with extensive brain damage (case 2), a small preterm infant with severe brain hemorrhage and likely extensive brain damage (case 3), and a term infant with trisomy 21 syndrome and a severe cardiac malformation (case 4). RESULTS: Major differences among the three religious opinions were found in the definition of viability and in the approach towards quality of life. CONCLUSIONS: Neonatologists must be sensitive to culture and religion when dealing with major ethical issues in the neonatal intensive care unit.

Reduced Hypoxic Tissue and Cognitive Improvement after Revascularization Surgery for Chronic Cerebral Ischemia.

BACKGROUND: Hypoxic but viable neural tissue is seen on 1-(2-18F-fluoro-1-[hydroxymethyl]ethoxy) methyl-2-nitroimidazole (18F-FRP170) positron emission tomography (PET) in patients with chronic cerebral ischemia with a combination of misery perfusion and moderately reduced oxygen metabolism. Cognitive function sometimes improves after revascularization surgery in patients with chronic cerebral ischemia. OBJECTIVES: We used brain perfusion single-photon emission computed tomography (SPECT) and 18F-FRP170 PET to determine whether hypoxic tissue was reduced following the restoration of cerebral perfusion after carotid endarterectomy (CEA) in patients with severe stenosis of the cervical internal carotid artery (ICA) and whether the reduction in hypoxic tissue was associated with cognitive improvement. METHOD: Eighteen patients with abnormally reduced cerebral blood flow (CBF) in the affected cerebral hemispheres on preoperative brain perfusion SPECT -underwent CEA. They underwent 18F-FRP170 PET and neuropsychological tests preoperatively and 6 months postoperatively. Brain perfusion SPECT was also performed 6 months postoperatively. Regions of interest were placed in the bilateral middle cerebral artery territories on SPECT and PET images, and the ratio of values in the affected versus contralateral hemispheres was calculated. RESULTS: The CBF ratio (p = 0.0006) and 18F-FRP170 ratio (p = 0.0084) were significantly increased and reduced, respectively, after surgery compared to the corresponding ratios before surgery. The difference in the 18F-FRP170 ratio (postoperative - preoperative value) was negatively correlated with the difference in the CBF ratio (ρ = -0.695; p = 0.0009). The difference in the 18F-FRP170 ratio was significantly lower in patients with postoperative improved cognition compared to that in those without (p = 0.0007). The area under the receiver operating characteristics curve for the difference in the 18F-FRP170 ratio for detecting postoperative improved cognition was significantly greater than that for the difference in the CBF ratio (difference between areas, 0.278; p = 0.0248). CONCLUSIONS: Hypoxic tissue is reduced following the restoration of cerebral perfusion with revascularization surgery in patients with severe atherosclerotic stenosis of the cervical ICA. The reduction in hypoxic tissue is associated with cognitive improvement in such patients.

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age.

Neonatal anoxia induces long-term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30-hour old pups to 100% nitrogen, represents a non-invasive and global stimulus, which simulates clinical conditions of human pre-term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety-like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious-like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia-induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyrus and CA1 subfields, but not in CA3-2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3-2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury.

Children sustaining a severe acquired brain lesion before age 3 years: a follow-up study at 1 year from insult.

PURPOSE: To describe the functional and cognitive outcome of acquired brain injury of different aetiologies in children before age 3 years, at initial hospitalization and at a 1-year follow-up, after a rehabilitation programme. METHOD: Data were collected at 6 months and at 12 months from the event; cognitive data were collected as soon as possible at T1. The full sample was divided into three groups according to aetiology. RESULTS: At T0, 74 patients showed so severe a cognitive impairment that they could not be evaluated, others presented with motor, linguistic and cognitive deficits. At T1, the proportion of non-evaluable patients decreased to 58 children. Patients with anoxic lesions showed the most unfavourable motor and visual outcome; patients with infectious lesions showed most frequently a motor global delay. CONCLUSIONS: At 1 year from insult about 50% of patients could undergo a cognitive evaluation. Improvement differed according to aetiology.

DSM-5 paraphilic disorders criteria in the light of autoerotic asphyxiophilia and non-sexual form of oxygen restriction. / Kryteria zaburzen parafilnych w DSM-5 wobec asfiksji autoerotycznej i pozaseksualnej formy ograniczania doplywu tlenu.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders published in 2013 has proved to be particularly interesting in the field of sexuality. It introduced a number of significant changes in the definition of sexual norms, among them a widely discussed distinction between paraphilias and paraphilic disorders. The key criterion separating the abnormal sexual interests from the disordered ones is clinically significant distress resulting directly from sexual behavior and/or the risk of suffering or harm to another person as a result of one's sexual behavior. In the case of masochism - which addresses the phenomenon of suffering quite particularly - this distinction is troublesome. Using the example of autoerotic asphyxia - a behavior from the masochism spectrum - the authors critically examine the proposed DSM-5 method of defining the standards of sexual behavior. Interesting in this regard has been a comparison between autoerotic asphyxia and free diving - a nonsexual activity which, although also associated with possible loss of life by reduction of oxygen, has not been pathologized.

Cognitive performance in transient global hypoxic brain injury due to moderate drowning.

INTRODUCTION: Drowning is a serious and frequently neglected public health threat. Primary respiratory impairment after submersion often leads to brain dysfunction. Depending on the period of global hypoxia (respiratory failure), clinical aspects of neurological dysfunction are evident on the first evaluation after the water rescue. Nowadays, many neuropsychological assessments after drowning are inconclusive, with some studies reporting only minor neurological or cognitive impairments. The aim of this study is to identify measures in neuropsychological tests that most contribute to classify volunteers as moderate drowning subjects or healthy controls. To the best of our knowledge, this study is the first neuropsychological prospective case-control study of moderate drowning in a country with large coastal cities. METHOD: Fifteen moderate drowning patients (DP), who met the inclusion criteria, were compared with 18 healthy controls (HC). All subjects were assessed on memory, learning, visual spatial ability, executive function, attention, and general intellectual functioning and underwent structural magnetic resonance (MR) imaging of the brain at 3.0 T, in order to exclude subjects with anatomic abnormalities. RESULTS: Neuropsychological tests assessing learning, execution function, and verbal fluency-Rey Auditory Verbal Learning Test (RAVLT) general learning ability, Digit Span total, Phonological Verbal Fluency (total FAS correct), and Brief Visuospatial Memory Test Revised (BVMT) correct recognition-have the strongest discriminating ability, using predictive models via the partial least squares (PLS) approach for data classification, while the other tests have shown similar predictive values between groups. CONCLUSIONS: Learning, execution function, and verbal fluency domains were the most critically affected domains. Serious impairments in the same domains have already been reported in severe drowning cases, and we hypothesize that subtle alterations found in moderate drowning cases, although not sufficient to be detected in daily routine, may possibly have a negative impact on cognitive reserve.

Hippocampal and cerebellar histological changes and their behavioural repercussions caused by brain ischaemic hypoxia experimentally induced by sodium nitrite.

INTRODUCTION: Brain ischaemic hypoxia can produce severe neurological damage that leads to behavioural disorders. This research analysed the hippocampal and cerebellar histological alterations caused by brain ischaemic hypoxia experimentally induced by sodium nitrite (NaNO2) and possible direct repercussions of this hypoxia on behaviour. METHODOLOGY: An experimental study was carried out by administering 60mg/kg NaNO2 to 10 Wistar rats at 3 months of age for 15 consecutive days. Ten control rats did not receive NaNO2. To assess behavioural repercussions, the animals were evaluated in Open Field, Elevated Plus-Maze (EPM), and Forced Swim tests before and after injury to evaluate locomotion, anxiety, and depression, respectively. Markers of stress were evaluated by measuring the blood levels of cortisol, glucose, cholesterol, and lactate. The presence of hippocampal lesions was verified by histologically studying the CA1-CA4 areas. Sections of the cerebellum were also evaluated because Purkinje cells are highly sensitive to ischaemic hypoxia and may serve as markers for this process. RESULTS: The number of neurons with lesions was significantly higher in animals exposed to NaNO2 in the hippocampus areas CA2, CA3, and CA4. The cerebellum was also very vulnerable to hypoxia, presenting extensive lesion áreas. These results are correlated with the parameters of the anxiety and depression tests. CONCLUSION: NaNO2 promoted brain damage due to ischaemic hypoxia in rats. Intoxicated animals showed decreased brain weights; damage in hippocampus and cerebellum; and anxiogenic and depressive behaviour.

Changes in impaired self-awareness after acquired brain injury in patients following intensive neuropsychological rehabilitation.

The objective of this study was to investigate changes in self-awareness impairments in outpatients with acquired brain injury (ABI) and the effects these changes have on rehabilitation. Participants were 78 patients with ABI (8.3 years post-injury) who followed an intensive outpatient neuropsychological rehabilitation programme. This longitudinal study comprised pre (T1) and post (T2) measurements and a one-year follow-up (T3). Thirty-eight patients completed the study. The main outcome domains were self-awareness, depressive symptoms, psychological and physical dysfunction, and health-related quality of life (HRQoL). Patients were divided into three awareness groups: underestimation, accurate estimation, and overestimation of competencies. Most patients who underestimated their competencies at the start of treatment accurately estimated their competencies directly after treatment (9 out of 11 patients). These patients also exhibited the largest treatment effects regarding depressive symptoms, psychological and physical dysfunction, and HRQoL. Most patients with impaired self-awareness (i.e., overestimation of competencies) at the start of treatment continued to overestimate their competencies after treatment (10 out of 14 patients). These patients exhibited a significant decrease in depressive symptoms but no other treatment effects. The results indicate that changes in outcome are related to changes in awareness, which underline the importance of taking into account different awareness groups with respect to treatment effects.

Amnesic patients show superior generalization in category learning.

OBJECTIVE: Generalization is the application of existing knowledge to novel situations. Questions remain about the precise role of the hippocampus in this facet of learning, but a connectionist model by Gluck and Myers (1993) predicts that generalization should be enhanced following hippocampal damage. METHOD: In a two-category learning task, a group of amnesic patients (n = 9) learned the training items to a similar level of accuracy as matched controls (n = 9). Both groups then classified new items at various levels of distortion. RESULTS: The amnesic group showed significantly more accurate generalization to high-distortion novel items, a difference also present compared to a larger group of unmatched controls (n = 33). CONCLUSIONS: The model prediction of a broadening of generalization gradients in amnesia, at least for items near category boundaries, was supported by the results. Our study shows for the first time that amnesia can sometimes improve generalization. (PsycINFO Database Record

Translational Challenge Models in Support of Efficacy Studies: Effect of Cerebral Hypoxia on Cognitive Performances in Rodents.

Empirical evidence currently supports the idea that neurovascular dysfunction is involved in the neurodegenerative process of Alzheimer's disease (AD). In fact, epidemiological studies report that i) vascular risk factors are directly associated with an increased incidence of AD and ii) vascular lesions are frequently co-existent with AD. The neurovascular unit is a key control system for oxygen and nutrients exchange between neurons and microvessels so the integrity of this system is essential for neuronal activity and cell survival. This suggests that hypoxia arising from various vascular injuries may participate in the pathogenesis of AD and aggravate cognitive deficit. Moreover, hypoxia appears to have a direct effect on cognitive functions, in particular memory, by inducing a transient or definitive dysfunction of synaptic transmission. The interplay of hypoxic phenomenon and the development of AD-related pathologies support the use of hypoxia as a challenge model to assess symptomatic (i.e. cognitive enhancers) AD-treatment. Such challenge should be characterized and validated with current symptomatic drugs based on different mechanisms of action before being offered as alternative models for testing new drugs. To date, symptomatic treatments of AD including anticholinesterasic- (donepezil, rivastigmine and galantamine) and antiglutamatergic- (memantine) drugs target various neurotransmission impairments occurring at different stages of the disease. The first aim of the present review is to provide an overview of the methods used to achieve experimental hypoxia in rodents and to characterize the cognitive alterations induced by each method. The second objective is to summarize the main results from studies that have tested the effect of acetylcholinesterase inhibitors on hypoxiainduced cognitive impairment. Overall, the literature research yielded only a small number of studies investigating the effect of hypoxia on cognition in rodents and the different models described sometime differ substantially in terms of timing, severity and nature of cognitive impairment. Chronic exposure to intermittent normobaric or continuous hypobaric hypoxia induced persistent spatial reference and working memory alterations. In contrast, acute hypoxia exposure was shown to induce more transient associative and spatial memory impairments. Treatment with acetylcholinesterase inhibitors was shown to improve hypoxia-induced memory impairment in various hypoxia protocols.