Psychometric Evaluation of Self-assessment Persian Version of the Alzheimer Questionnaire (AQ).

Introduction: Mild cognitive impairment (MCI) is a primary disorder intensified by aging. Rapid diagnosis of MCI can prevent its progression towards the development of dementia. Thus, the present study was conducted to evaluate the psychometric features of the self-assessment Persian version of the Alzheimer questionnaire (AQ) in the elderly to detect MCI. Methods: First, the AQ was translated into the Persian language; then, its content validity was evaluated by the content validity index (CVI) and content validity ratio (CVR) method, and face validity was determined by two checklists for expert panel and the elderly. The convergent validity of the self-assessment AQ with the Montreal cognitive assessment (MoCA) was assessed using the Pearson correlation. The test-retest and internal consistency reliability were evaluated using intra-class correlation (ICC) and Kuder-Richardson coefficients, respectively. Moreover, the receiver operating characteristic curve was used to determine the optimal cut-off point of self-assessment AQ. Among 148 older people who took part in this study, 93 met our inclusion criteria (aged 60 years old or older, had reading and writing skills, and were able to speak and communicate). Results: A translated version of the questionnaire was named "M-check." The developed test showed good content and face validity. Statistically significant correlations were found between M-check and MoCA (r=-0.83, P<0.05). The Kuder-Richardson and ICC coefficients were obtained as 0.84 and 0.92, respectively. Area under the curve presented satisfactory values (Area under curve [AUC]=0.852, sensitivity=0.62, specificity=0.94). Conclusion: The M-check can be used as a valid and reliable instrument for assessing cognitive state and screening MCI in older adults. Highlights: All questions achieved desired face validity.The convergent validity of Alzheimer Questioner (AQ) was confirmed with high correlation.The AQ is statistically significant with Montreal Cognitive Assessment (MoCA).The AQ had acceptable stability, repeatability, and reliability.All findings demonstrated that the M-Check had high values in predicting MCI in the early stages. Plain Language Summary: Mild cognitive impairment (MCI) is a subset of mental disorders that is an early condition that may lead to dementia. People with MCI are usually prone to forgetfulness in a short time. If MCI is not detected in the early stages, it can progress to dementia or Alzheimer's to higher degrees. On the other hand, cognitive decline and MCI can cause major problems for patients and their families. So it is essential to act out as soon as possible. It is considered that a tool for the early identification of MCI that is self-assessed by individuals, without the presence of an expert and trained person to interpret the results, was not observed in Iran. Thus, the present study was conducted to evaluate the psychometric features of the self-assessment Persian version of the Alzheimer questionnaire (AQ) in the elderly. The results showed that the AQ is a simple one that can be quickly completed by any person at home or by family members of the elderly so that people can refer to the relevant specialist more soon if needed.

Peroxisome proliferator-activated receptor-γ doesn't modify altered electrophysiological properties of the CA1 pyramidal neurons in a rat model of hepatic cirrhosis.

Regarding the low quality of life due to the cognitive complications in the patients with hepatic cirrhosis (HC), the goal of this study was to examine the possible neuroprotective effect of pioglitazone (PIO) on the electrophysiological alterations of hippocampus, a major area of cognition, in the experimental model of bile duct ligation (BDL). We used adult male Wistar rats in the present study to perform BDL or sham surgery. Pioglitazone was administered in BDL rats two weeks after the surgery for the next continuous four weeks. The effects of pioglitazone on BDL-induced electrophysiological alterations of the CA1 pyramidal neurons in the hippocampus were evaluated by whole-cell patch clamp recordings. Our findings demonstrated that chronic administration of PIO could not reverse the electrophysiological changes in the CA1 pyramidal neurons of the hippocampus in BDL rats but could improve the hepatic dysfunction.Together, the results of this study suggest that PIO administration cannot counteract altered intrinsic properties of the hippocampal neurons which has been shown recently as an involved mechanism of the cognitive impairments in hepatic encephalopathy (HE).

Erythropoietin attenuates locomotor and cognitive impairments in male rats subjected to physical and psychological stress.

Physical and cognitive problems associated with stress are believed to result from stress-related damage to neurons involved in motor and cognitive control. In general, there are two types of stress, physical and psychological which both negatively impact neuronal function. Erythropoietin (EPO) has been shown to exert a neuroprotective effect in various models of physical brain injury; however, its actions on stress-related changes in behavior are unknown. The aim of the current study was to determine whether EPO ameliorated stress-induced locomotor and cognitive impairments, and to compare the effects of EPO on behavioral changes induced by the two different types of stressors. In this study, male Wistar rats were randomly divided into five groups and placed under physical or psychological stress for 10 consecutive days while erythropoietin was injected intraperitoneally (i.p.) every other day (500 U/kg/i.p.) 30 min before stress induction. Exploratory, anxiety-related behaviors, learning and memory were assessed by using open field, plus maze and Morris Water Maze (MWM) tests respectively. Our data showed physical and psychological stress induced dysfunction in locomotion, reduced explorative skills, heightened anxiety-like behavior and reduced memory, which could be partly reversed by EPO. We conclude that EPO reduces adverse effects of both psychological and physical stress, putatively through protection of locomotor and cognitive-controlling neurons vulnerable to the damaging effects of stress. However, future studies need to elucidate the neural mechanisms of the protective effects of EPO.

Caspase-3: Structure, function, and biotechnological aspects.

Caspase-3, a cysteine-aspartic acid protease, has recently attracted much attention because of its incredible roles in tissue differentiation, regeneration, and neural development. This enzyme is a key zymogen in cell apoptosis and is not activated until it is cleaved by initiator caspases during apoptotic flux. Since caspase-3 has represented valuable capabilities in the field of medical research, biotechnological aspects of this enzyme, including the production of recombinant type, protein engineering, and designing delivery systems, have been considered as emerging therapeutic strategies in treating the apoptosis-related disorders. To date, several advances have been made in the therapeutic use of caspase-3 in the management of some diseases such as cancers, heart failure, and neurodegenerative disorders. In the current review, we intend to discuss the caspase-3's structure, functions, therapeutic applications, as well as its molecular cloning, protein engineering, and relevant delivery systems.

Electrophysiological and inflammatory changes of CA1 area in male rats exposed to acute kidney injury: Neuroprotective effects of erythropoietin.

The high mortality rate associated with acute kidney injury (AKI) is commonly due to progressive, inflammatory multiple organ dysfunction, which often involves neurological complications. The AKI-stimulated mechanisms leading to brain dysfunction are not well understood, which hinders development of new therapeutic avenues to minimize AKI-mediated neural effects. The hippocampal CA1 area is a particularly vulnerable region during AKI but the electrophysiological and inflammatory mechanisms involved in this vulnerability remain largely unknown. Here, we used immunohistochemistry to quantitatively investigate the number of astrocytes expressing glial fibrillary acidic protein (GFAP) as an indicator of inflammation, and whole cell patch clamp to evaluate electrophysiological changes in CA1 at different time points following induction of bilateral renal ischemia (BRI) in male Wistar rats. Further we evaluated the effectiveness of erythropoietin (EPO, 1000 U/kg i.p.) in mitigating BRI-associated changes. Plasma concentrations of blood urea nitrogen (BUN) were significantly enhanced at 24 h, 72 h and 1 week, and creatinine (Cr) was increased at 24 h after reperfusion, which were changes reduced by EPO. BRI led to an increase in CA1 GFAP-positive cells 24 h and 72 h, but not 1 week, after reperfusion, and EPO reversed this effect of BRI at 24 h. Additionally, BRI caused an increase in the peak amplitude and coefficient of variation of CA1 pyramidal neuronal action potentials, which were changes not seen in presence of EPO. When taken together, altered neuronal electrophysiological properties and astrogliosis could contribute to the neurological complications induced by AKI, and EPO offers hope as a potential neuroprotective agent.

Ophthalmic manifestations of COVID-19; a less-appreciated yet significant challenge.

AIM: The current world has changed in all shapes since the emergence of the novel coronavirus (nCoV-2) also known as COVID-19. Among the extra-pulmonary manifestations of nCoV-2, ophthalmic symptoms have less been systematically studied. The so far existing body of evidence indicates that nCoV-2 has the potential to affect both anterior and posterior chambers of the eye. Albeit, the exact mechanisms which underlie ophthalmic manifestations of nCoV-2 are yet to be elucidated. METHODS: The present brief review is an attempt to put together and highlight the significant yet limited number of studies which have spotlighted ophthalmic issues in nCoV-2 patients using a systematic literature search strategy. RESULTS: All case series or reports (including both published and preprint articles) which described ocular manifestations of patients with COVID-19 and/or documented testing of SARS-COV-2 in ocular secretions via various sampling or detection methods were sought to be included. CONCLUSION: The ophthalmic presentations in SARS-COV-2 are often found to be salient. Raising awareness in this respect may help defining evidencebased protective measures in today's practice of ophthalmology and allied disciplines.

Ischemic Postconditioning Attenuates Bilateral Renal Ischemia-induced Cognitive Impairments.

Introduction: Acute Kidney Injury (AKI) is a frequent complication of kidney failure with high mortality, leading to brain dysfunction. This study aimed to investigate the possible protective effect of Ischemic Postconditioning (IPo) against brain dysfunction induced by Bilateral Renal Ischemia (BRI). Methods: Male Wistar rats underwent BRI, sham, or IPo surgery 24h and 1w after reperfusion. The rats' explorative behaviors and motor function were evaluated by an open field, rotarod, and wire grip tests. The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Western blotting was performed to evaluate hippocampal Brain-Derived Neurotrophic Factor (BDNF) expression. Results: The impairment of balance function induced by BRI was not reversed; however, passive avoidance learning impairment was reversed by postconditioning 24h after reperfusion. IPo increased muscle strength compared to the BRI group; however, explorative behaviors and balance function had no difference 1w after reperfusion. BRI significantly decreased the BDNF protein expression in the hippocampus, and postconditioning increased 24h after reperfusion. Conclusion: The obtained results demonstrated the deleterious effect of BRI on cognitive and balance function 24h after reperfusion. IPo indicated a curative effect against cognitive dysfunction probably by enhancing BDNF protein expression in the hippocampus. Highlights: IPo improved passive avoidance learning impairment induced by BRI.IPo increased muscle strength compared to the BRI group.BRI significantly decreased the BDNF protein expression in the hippocampus.IPo increased BDNF protein expression 24h after reperfusion. Plain Language Summary: Acute kidney injury may be associated with numerous complications in different regions of brain, as it may alter the permeability of the blood-brain barrier, accumulate the toxins, decreased blood flow to the brain, increased risk of encephalopathy, higher mental dysfunctions like delirium, stroke, memory and thinking problems (dementia) in people with kidney failure. It has been demonstrated that the most common causes of mortality in acute kidney injury is brain dysfunction. Therefore, discovering new treatments can decrease the brain injuries and help the patients with kidney dysfunction to have a higher quality of life. Ischemic postconditioning, which refers to a series of brief ischemia and reperfusion cycles applied immediately at the site of the ischemic organ after reperfusion, results in reduced injuries induced by ischemia. The purpose of the current study was designed to investigate whether ischemic postconditioning exerts neuroprotective effects against brain dysfunctions induced by renal ischemia in rats. Results of this study demonstrated that acute kidney injury triggers distant organ dysfunction and leads to cognitive and balance dysfunction 24h after induction of renal ischemia and ischemic postconditioning protects the brain as a remote organ against cognitive dysfunction from the injury induced by renal ischemia.

Studies on the Bottom-Up and Top-Down Neural Information Flow Alterations in Neurodegeneration.

BACKGROUND: A proper explanation for perceptual symptoms in neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD) is still lacking. OBJECTIVE: This study aimed at investigating the imbalance between 'bottom-up' and 'top-down' information flow (IF) and processing in PD in relation with visual hallucination symptoms. METHODS: Here, we looked at bottom-up and top-down IF markers using resting state electroencephalographic (EEG) data from PD patients analyzed through three different IF measures (direct Directed Transfer Function (dDTF), full frequency Directed Transfer Function (ff-DTF), and renormalized Partial Directed Coherence (rPDC). RESULTS: We observed an increased gamma band IF and a reduced beta band IF in PD patients compared to healthy controls. Additionally, we noticed a reduced theta band IF in PD patients using dDTF as a measure of IF. By source localizing the EEG activity of the PD patients and healthy controls, we looked at the alterations of IF in the prefrontal cortex of PD patients as well. CONCLUSION: In line with previous studies, our results suggest that the delicate balance between bottom-up and top-down IF is disrupted in Parkinson's disease potentially contributing to the cognitive symptoms of PD patients.

Pre-Treatment with Erythropoietin Attenuates Bilateral Renal Ischemia-Induced Cognitive Impairments.

One of the most common causes of mortality in acute kidney injury is brain dysfunction. Here we investigated the possible protective effect of erythropoietin (EPO) on cognitive impairments induced by bilateral renal ischemia (BRI). Eighty male Wistar rats were allocated into 8 groups: 1, 2) Sham +V (Vehicle), 3, 4) Sham+EPO, 5, 6) BRI+V, 7, 8) BRI+EPO. The groups followed by the reperfusion periods of 24hours (24 h) and 1week (1w). EPO or saline was administrated 30 min before surgery (1000 IU/kg, i.p). The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Hippocampal brain-derived neurotrophic factor (BDNF) protein expression was assessed by western blotting. BUN (blood urea nitrogen) and creatinine (Cr) concentrations were significantly increased in BRI+V group 24 h after reperfusion. BRI+V rats had just an increased level of BUN but not Cr 1w after reperfusion. EPO reversed passive avoidance learning impairments observed in BRI+V group 24 h after reperfusion. There were no significant differences in spatial and passive avoidance learning between experimental groups 1w after reperfusion and histological evaluation confirmed the behavioral data. BRI significantly decreased the BDNF protein expression in the hippocampus and EPO increased that 24 h after operation. These observations showed protective effect of EPO against cognitive dysfunctions following BRI 24 h after reperfusion through increase in BDNF protein expression.

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties.

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.

Erythropoietin attenuates motor impairments induced by bilateral renal ischemia/reperfusion in rats.

Neurologic sequelae remain a common and destructive problem in patients with acute kidney injury. The objective of this study was to evaluate the possible neuroprotective effect of erythropoietin (EPO) on motor impairments following bilateral renal ischemia (BRI) in two time points after reperfusion: short term (24 h) and long term (1 week). Male Wistar rats underwent BRI or sham surgery. EPO or saline administration was performed 30 min before surgery (1000 U/kg, i.p.). Explorative behaviors and motor function of the rats were evaluated by open field, rotarod, and wire grip tests. Plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were significantly enhanced in BRI rats 24 h after reperfusion. BRI group had only an increased level of BUN but not Cr 1 week after reperfusion. Impairment of balance function by BRI was not reversed by EPO 24 h after reperfusion, but counteracted 7 days after renal ischemia. Muscle strength had no significant differences between the groups. BRI group had a decrease in locomotor activity, and EPO could not reverse this reduction in both time points of the experiment. Although EPO could not be offered as a potential neuroprotective agent in the treatment of motor dysfunctions induced by BRI, it could be effective against balance dysfunction 1 week after renal ischemia.

Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor.

Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments were studied. Adult rats were treated with WIN (0.5mg/kg; i.p.) 15min before harmaline administration (10mg/kg; ip) after which exploratory and anxiety related behaviors, and cognitive function were assessed using open-field behavior and shuttle box tests. Rats that received harmaline only exhibited a markedly reduced number of central square entries when compared to harmaline vehicle-treated controls, whereas those treated with WIN and harmaline showed a significant increase in central square entries, compared to harmaline only treated. The passive avoidance memory impairments observed in harmaline treated rats, was reversed somewhat by administration of WIN. The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions.

Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

BACKGROUND: There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. METHODS: Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. RESULTS: In NORT, the discrimination ratio was decreased after ischemia (P < 0.05) and exercise preconditioning improved it in ischemic animals. In the passive avoidance test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P < 0.001). In the adhesive removal test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P < 0.001) and exercise preconditioning decreased these indices compared to the ischemic group (all P < 0.001). In the ledged beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). CONCLUSION: Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.