Improvement of Upper Limb Motor Control and Function After Competitive and Noncompetitive Volleyball Exercises in Chronic Stroke Survivors: A Randomized Clinical Trial.

OBJECTIVES: To investigate the effects of competitive and noncompetitive volleyball exercises on the functional performance and motor control of the upper limbs in chronic stroke survivors. DESIGN: Randomized clinical trial. SETTING: Outpatient rehabilitation center. PARTICIPANTS: Chronic stroke survivors (N=48). INTERVENTIONS: Participants were randomly assigned to competitive (n=16) or noncompetitive (n=16) volleyball exercise groups (60min/d volleyball exercise+30min/d traditional rehabilitation, 3d/wk for 7wk) and control group (n=16). MAIN OUTCOME MEASURES: Reach and grasp motor control measures were evaluated through kinematic analysis. Functional outcomes were assessed via Motor Activity Log, Wolf Motor Function Test (WMFT), Box and Block Test, and Wrist Position Sense Test. RESULTS: Significant improvement of functional performance was observed in both competitive (P<.0001) and noncompetitive volleyball exercise groups (P<.01), but not in the control group (P>.05), with the exception of WMFT score. Volleyball training, in general, resulted in more efficient spatiotemporal control of reach and grasp functions, as well as less dependence on feedback control as compared to the control group. Moreover, the competitive volleyball exercise group exhibited greater improvement in both functional performance and motor control levels. CONCLUSIONS: Volleyball team exercises, especially in a competitive format, resulted in enhancing the efficacy of the preprogramming and execution of reach and grasp movements, as well as a shift from feedback to feedforward control of the affected upper limb in chronic stroke survivors. This may well be a potential underlying mechanism for improving functional performance.

Can Postural Instability in Individuals with Distal Radius Fractures Be Alleviated by Concurrent Cognitive Tasks?

BACKGROUND: Although impaired postural control may be a risk factor for distal radius fractures (wrist fractures), which often are caused by falls, little attention has been given thus far to the various performance and neurophysiologic aspects involved. Although studies suggest that external focus and cognitive tasks can improve postural control, it remains unclear whether these benefits are observed in individuals with a history of distal radius fracture and to what extent. QUESTIONS/PURPOSES: (1) To compare patients with a history of distal radius fracture to age- and sex-matched controls in terms of postural stability while standing on stable and unstable support surfaces, using both postural sway and neurophysiological measures as endpoints; and (2) to determine whether internal- and external-focus strategies and cognitive tasks can improve postural stability in these patients. METHODS: Forty patients with distal radius fracture (33 females and seven males with a mean ± SD age of 56 ± 4 years) and 40 sex- and age-matched control participants participated in the study. We recruited patients with a history of fall-induced distal radius fractures occurring between 6 and 24 months before the start of our study. We excluded patients who had any of the following: fear of falling, taking any medication that may affect balance, neurologic disorders, dizziness, vestibular problems, Type II diabetes, musculoskeletal disorders or recent history of lower extremity fracture, any recent surgical interventions in the spine or lower limbs, and/or cognitive impairment. Of 120 patients who were being treated for distal radius fracture over the 18-month period, 91 (76%) agreed to participate and 40 eligible patients were finally enrolled. The control group included sex- and age-matched (within 2-year intervals) individuals who had never had a wrist fracture. This group was selected from attendants/relatives of the patients attending the neurology and physical medicine and rehabilitation outpatient departments, as well as other volunteers with no history of balance problems or wrist fractures. To address our primary research question, we compared the postural control of individuals with a history of distal radius fracture with the control group while quietly standing on different support surfaces (rigid and foam surfaces) using both postural sway measures obtained by a force plate as well as neurophysiological measures (electromyography [EMG] activity of tibialis anterior and medial gastrocnemius). To address our secondary research question, we compared the postural sway measures and EMG activity of the ankle muscles between different experimental conditions (baseline, internal focus (mentally focusing on their feet without looking), external focus (mentally focusing on rectangular papers, placed on the force plate or foam, one under each foot), difficult cognitive task (recalling maximum backward digits plus one) and easy cognitive task (recalling half of the maximum backward digits). RESULTS: Patients with distal radius fractures presented with greater postural sway (postural instability) and enhanced ankle muscle activity compared with their control counterparts, but only while standing on a foam surface (mean velocity: 5.4 ± 0.8 versus 4.80 ± 0.5 [mean difference = 0.59, 95% CI of difference, 0.44-0.73; p < 0.001]; EMG root mean square of the tibialis anterior: 52.2 ± 9.4 versus 39.30 ± 6 [mean difference = 12.9, 95% CI of difference, 11.4-14.5; p < 0.001]). Furthermore, a decrease in postural sway was observed while standing on both rigid and foam surfaces during the external focus, easy cognitive, and difficult cognitive conditions compared with the baseline (for example, mean velocity in the baseline condition compared with external focus, easy cognitive task and difficult cognitive task was: 4.9 ± 1.1 vs 4.7 ± 1 [mean difference = 0.14, 95% CI of difference, 0.11-0.17; p < 0.001], 4.6 ± 1 [mean difference = 0.25, 95% CI of difference, 0.21-0.29; p < 0.001], and 4.5 ± 1 [mean difference = 0.34, 95% CI of difference, 0.29-0.40; p < 0.001] in the wrist fracture group). The same result was obtained for muscle activity while standing on foam (EMG root mean square of tibialis anterior in the baseline condition compared with external focus, easy cognitive task and difficult cognitive task: 58.8 ± 7.2 versus 52.3 ± 6.6 [mean difference = 6.5, 95% CI of difference, 5.5-7.6; p < 0.001], 48.8 ± 7.1 [mean difference = 10.1, 95% CI of difference, 9-11.1; p < 0.001], 42.2 ± 5.3 [mean difference = 16.7 95% CI of difference, 15.1-18.2; p < 0.001] in the wrist fracture group). CONCLUSIONS: The current results suggest that patients with a history of distal radius fractures have postural instability while standing on unstable support surfaces. This instability, which is associated with enhanced ankle muscle activity, conceivably signifying an inefficient cautious mode of postural control, is alleviated by external attention demands and concurrent cognitive tasks. CLINICAL RELEVANCE: The findings of this study may serve as a basis for designing informed patient-specific balance rehabilitation programs and strategies to improve stability and minimize falls in patients with distal radius fractures. The integrative methodology presented in this work can be extended to postural control and balance assessment for various orthopaedic/neurological conditions.

Effects of cognitive load on the amount and temporal structure of postural sway variability in stroke survivors.

This study aimed to investigate the variability in postural sway patterns during quiet standing in stroke survivors. The postural sway was measured in 19 stroke survivors, as well as 19 healthy demographically matched participants, at 3 levels of postural difficulty (rigid surface with closed and open eyes, and foam surface with closed eyes), and 3 levels of cognitive difficulty (without a cognitive task, easy and difficult cognitive tasks). Both linear analyses (the amount of postural sway variability, including the standard deviation of the COP velocity in both the anteroposterior (AP) and mediolateral (ML) directions), as well as non-linear analyses [the temporal structure of the COP variability, including % Recurrence, % Determinism, Shannon Entropy, Trend and the maximum diagonal line (D max)] were employed. The results revealed that the amount of variability of the postural sway of stroke survivors was significantly greater than that of healthy participants, along both the ML and AP directions, with the highest obtained during standing on foam with closed eyes. All measures of the temporal structure of the COP variability were significantly greater in stroke survivors, as compared to the control group, along the ML direction, but not along the AP direction. The cognitive error was significantly higher during difficult cognitive tasks, although it was neither affected by postural difficulty nor by group. The different results obtained for the amount and temporal structure of the COP variability in the AP and ML directions shed light on the intricate mechanisms employed by the CNS in post-stroke balance control, and suggest that effective rehabilitative and therapeutic strategies should be patient-specific, taking both the environment/surface as well as the specific protocols into consideration.

The effects of a short-term memory task on postural control of stroke patients.

BACKGROUND: Many studies have been conducted on the changes in the balance capabilities of stroke patients. However, results regarding the effects of dual-task activities on postural control in these patients have been variable. OBJECTIVE: To evaluate the effects of a short-term memory task on the sway characteristics of stroke patients. METHOD: Center of pressure (COP) fluctuations were measured in three levels of postural difficulty (rigid surface with closed and open eyes and foam surface with closed eyes), as well as two levels of cognitive difficulty (easy and difficult). COP parameters included mean velocity, standard deviation of velocity in both medial-lateral (M.L) and anterior-posterior (A.P) directions, total phase plane portrait, area. Nineteen stroke patients and 19 gender, age, height, and weight matching healthy volunteers participated in this study. RESULTS: Our findings indicate that mean velocity (F = 14.21, P = 0.001), standard deviation of velocity in both M.L (F = 17.50, P = 0.000) and A.P (F = 11.03, P = 0.002) directions, total phase plane portrait (F = 44.12, P = 0.001), and area (F = 13.95, P = 0.01) of center of pressure of patients were statistically greater than normal subjects, while significant interaction of group × postural difficulty and postural × cognitive difficulty were observed for all parameters of postural sway. CONCLUSIONS: Different measures of postural sway showed complex response to postural and cognitive difficulties between stroke patients and normals. Cognitive error was not affected by the main effects of group and postural difficulty, while greatly increased at more difficult cognitive task (F = 75.73, P = 0.000).

Patient with a history of Glanzmann thrombasthenia presented with chronic subdural hematoma: a case report study.

Glanzmann thrombasthenia (GT) is a rare platelet disorder characterized by qualitative/quantitative deficiencies of the platelets' fibrinogen receptor, glycoprotein (GP) IIb/IIIa complex, resulting in impaired platelet aggregation and increased bleeding time. Most cases are hereditary with an autosomal recessive pattern of inheritance, but acquired GT also occurs. We report the surgical management of symptomatic chronic subdural hematoma (CSDH), a rare condition in young individuals, in a 37-year-old man who had GT and a history of mild head trauma approximately one month before admission. Despite hematologic consultation, normal bleeding time and clotting time, and platelet transfusion before surgery, massive hemorrhage during surgery, epidural hematoma, and anisocoria in the ICU occurred that led to craniectomy. This report highlights that CSDH management in patients with GT requires close monitoring of these patients as well as collaboration between neurosurgeons, intensive care physicians, hematologists, and anesthesiologists.

Lille Apathy Rating Scale-Patient Version in Stroke Survivors: Psychometric Properties and Diagnostic Accuracy.

OBJECTIVES: This study evaluated the factorial structure, psychometric properties, and diagnostic accuracy of the Persian version of the Lille Apathy Rating Scale-Patient version (LARS-P) in stroke survivors. PARTICIPANTS: This study comprised 105 stroke survivors and 41 healthy controls. METHODS AND SETTING: Exploratory factor analysis was used to determine the factors of the LARS-P. The acceptability, reliability, and validity of the LARS-P were also assessed. Agreement between the LARS-P and the Lille Apathy Rating Scale-informed version (LARS-I) was evaluated using the Bland-Altman plot. The diagnostic accuracy of the LARS-P was determined by categorizing stroke survivors into apathetic and nonapathetic groups based on the "diagnostic criteria of apathy." RESULTS: The exploratory factor analysis showed 3 factors (action initiation and social life; novelty and motivation; and emotional and self-awareness), explaining 67.35% of the variance. Cronbach's alpha was 0.85 for between-items and 0.74 for between-subscales. Intra-class correlation coefficient (ICC)2,1 was >0.88 for test-retest and inter-rater reliability. The LARS-P showed moderate to strong correlations with the LARS-I and Neuropsychiatric Inventory-Apathy subscale (r = 0.70-0.82). In addition, the LARS-P had significant moderate correlations with 2 subscales of the Hospital Anxiety and Depression Scale, modified Rankin Scale, Barthel Index, and Lawton Instrumental Activities of Daily Living (r or Æ¿ = 0.47-0.63). There was a 96.19% agreement between LARS-P and LARS-I. The identified cutoff point (>17) for LARS-P exhibited 77.14% sensitivity and 90% specificity in diagnosing apathetic and nonapathetic stroke survivors. CONCLUSIONS AND IMPLICATIONS: The LARS-P exhibits acceptable psychometric properties in stroke survivors, presenting a promising instrument for assessing apathy through a multidimensional framework.

Apathy exacerbates postural control impairments in stroke survivors: The potential effects of cognitive dual-task for improving postural control.

Apathy is a stressor and debilitating common condition for both stroke survivors and their caregivers. However, its effects on the postural control of these patients have not yet been investigated. Improved postural stability through withdrawing attention from postural control by concurrent cognitive task (i.e. dual-task condition) has been reported previously, but the effect of apathy, as a confounding factor, remains unknown. This study aimed to examine the effects of apathy and dual-task condition on postural control of chronic stroke survivors from biomechanical and neurophysiological perspectives. Twenty non-apathetic stroke survivors, 20 apathetic stroke survivors, and 20 sex-, age-, weight-, and height-matched healthy subjects were assessed using different postural sway measures and electromyography activity of ankle and hip muscles while quietly standing on rigid and foam surfaces under single-task, easy dual-task, and difficult dual-task conditions. The results showed postural instability and neuromuscular stiffening of stroke survivors, particularly apathetic stroke survivors, compared with healthy controls as evidenced by significantly greater postural sway measures and increased co-contraction of ankle muscles as well as hip muscles. Notably, concurrently performing a cognitive task significantly reduced postural instability and neuromuscular stiffening in chronic stroke survivors even in those with apathy. In conclusion, apathy exacerbates postural control impairments in chronic stroke survivors promoting an inefficient conscious mode of postural control. It is recommended that distracting the attention away from postural control by performing a concurrent cognitive task can be considered an effective strategy while designing interventions for improving postural control in apathetic stroke survivors.

Staging of cognitive impairment in Parkinson's disease: validity of Quick Dementia Rating System.

PURPOSE: This study aimed to investigate the ability of the Quick Dementia Rating System (QDRS) to discriminate patients with PD who have mild cognitive impairment from those without cognitive impairment and those with dementia. METHOD: A total of 105 patients with PD were classified as without cognitive impairment (N = 32), with mild cognitive impairment (N = 23), and PDD (N = 50), according to their score on clinical dementia rating. Multivariate regression analysis was performed considering age, education, and disease severity as covariates and mild cognitive impairment or dementia as outcome variables. Receiver operating characteristic curve analysis was carried out to derive the optimal cut-off points. RESULTS: The cut-off point >2.5 (sensitivity = 86.96%, area under curve (AUC) = 0.88) was obtained for discriminating patients with mild cognitive impairment from those without cognitive impairment based on the total score of QDRS. The cut-off point >5 (sensitivity = 84%, AUC = 0.84) was derived for discriminating mild cognitive impairment from dementia based on the total score of QDRS. CONCLUSIONS: The results of this study showed a good discriminative validity of the QDRS for discriminating mild cognitive impairment from no cognitive impairment and dementia in patients with PD.IMPLICATIONS FOR REHABILITATIONThe Quick Dementia Rating System has a good discriminative validity for diagnosing mild cognitive impairment from normal cognitive function in Parkinson's disease.The Quick Dementia Rating System has a good discriminative validity for diagnosing mild cognitive impairment from dementia in Parkinson's disease.The Quick Dementia Rating System could be suggested as a routine rapid cognitive screening tool for patients with Parkinson's disease.

Reliability, validity, and diagnostic accuracy of Parkinson's Disease-Cognitive Rating Scale in Iranian patients with idiopathic Parkinson's disease.

PURPOSE: To investigate the reliability and validity of Parkinson's Disease-Cognitive Rating Scale (PD-CRS) in Iranian patients with idiopathic PD. METHODS: One hundred and eighty patients with PD and 60 age-, gender-, and educational level-matched healthy individuals participated in this study. Inter-rater and test-retest reliability of the Persian version of PD-CRS was investigated in 80 patients with PD. To evaluate the construct validity of the PD-CRS, its correlation with the Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog), Mini-Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, Unified Parkinson's Disease Rating Scale-Section I, and Quick Dementia Rating System was assessed. To assess the diagnostic accuracy of the PD-CRS, patients with PD were classified as groups with normal cognitive function, mild cognitive impairment (MCI), and dementia using the Clinical Dementia Rating. RESULTS: Test-retest and inter-rater reliability (ICC > 0.90), as well as internal consistency (α = 0.94) of the Persian version of PD-CRS, were excellent. A high positive correlation was found between the PD-CRS and SCOPA-Cog. A cut-off point of ≤79 (sensitivity 98.15% and specificity 98.04%) and ≤62 (sensitivity 100%, and specificity 100%) on the PD-CRS total score was obtained for detecting MCI and dementia in PD patients, respectively. CONCLUSIONS: The results of this study showed that the Persian version of PD-CRS is a reliable and valid measure with high sensitivity and specificity to identify MCI and dementia in patients with PD.Implications for rehabilitationThe PD-CRS has an excellent test-retest and inter-rater reliability and validity in Iranian patients with PD.The PD-CRS has high sensitivity and specificity for discriminating between different levels of cognitive impairment (i.e. no cognitive impairment, mild cognitive impairment, and dementia) in Iranian patients with PD.

Overload of anxiety on postural control impairments in chronic stroke survivors: The role of external focus and cognitive task on the automaticity of postural control.

BACKGROUND: Despite the high prevalence of anxiety among chronic stroke survivors and evidence of its negative effects on postural control in healthy subjects, it is unclear whether anxiety also affects postural control in these patients. Recent evidence of improved postural control of healthy subjects by distracting the attention using an external focus (EF) or cognitive task, raises the question of whether similar benefits would be observed in stroke survivors. Thus, the current study aimed to investigate the effects of anxiety and distracting the attention on postural control of chronic stroke survivors in terms of both postural sway measures and neuromuscular regulation. METHODS: Postural sway measures and ankle muscle activity of chronic stroke survivors with the high and low level of anxiety (HA-stroke (n = 17), and LA-stroke (n = 17), respectively) and age-, sex-, height-, and weight-matched healthy subjects (n = 17) were assessed while standing on rigid and foam surfaces under following conditions: baseline, internal focus (IF), EF, simple and hard cognitive tasks (SC and HC, respectively). RESULTS: Stroke survivors, particularly HA-stroke participants, showed greater postural sway measures (i.e. postural instability) and enhanced co-contraction of ankle muscles (i.e. stiffening of the neuromuscular system) compared with healthy subjects. As opposed to baseline and IF conditions, postural instability and neuromuscular stiffening significantly reduced in EF condition and decreased more in cognitive task conditions, particularly HC condition. CONCLUSIONS: The results suggest that anxiety enhances stroke-induced postural instability promoting improper neuromuscular control of posture with stiffening strategy, which can be alleviated by EF and cognitive tasks.

Anxiety and cognitive load affect upper limb motor control in Parkinson's disease during medication phases.

Anxiety is among the most debilitating nonmotor symptoms of Parkinson's disease (PD). This study aimed to determine how PD patients with low and high levels of anxiety (LA-PD and HA-PD, respectively) compare with age- and sex-matched controls at the level of motor control of reach-to-grasp movements during single- and dual-task conditions with varying complexity. Reach-to-grasp movement kinematics were assessed in 20 LA-PD, 20 HA-PD, and 20 sex- and age-matched healthy controls under single- as well as easy and difficult dual-task conditions. Assessment of PD patients was performed during both the on- and off-drug phases. The results obtained during dual-task conditions reveal deficits in both reach and grasp components for all three groups (e.g., decreased peak velocity and delayed maximum hand opening). However, these deficits were significantly greater in the PD groups, especially in the HA-PD group. Although dopaminergic medication improved reach kinematics, it had no effect on grasp kinematics. The results of our study indicated that high levels of anxiety may enhance the inefficiency of upper limb motor control in PD patients, especially during high demanding cognitive conditions, and should, therefore, be considered in the assessment and planning of interventions for upper limb function in these patients.

Bucladesine Attenuates Spatial Learning and Hippocampal Mitochondrial Impairments Induced by 3, 4-Methylenedioxymethamphetamine (MDMA).

Neurotoxic effects of systemic administration of 3, 4- methylenedioxymethamphetamine (MDMA) has been attributed to MDMA and its metabolites. However, the role of the parent compound in MDMA-induced mitochondrial and memory impairment has not yet been investigated. Moreover, it is not yet studied that analogs of 3', 5'-cyclic adenosine monophosphate (cAMP) could decrease these neurotoxic effects of MDMA. We wished to investigate the effects of the central administration of MDMA on spatial memory and mitochondrial function as well as the effects of bucladesine, a membrane-permeable analog of cAMP, on these effects of MDMA. We assessed the effects of pre-training bilateral intrahippocampal infusion of MDMA (0.01, 0.1, 0.5, and 1 µg/side), bucladesine (10 and 100 µM) or combination of them on spatial memory, and different parameters of hippocampal mitochondrial function including the level of reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outer membrane damage, the amount of cytochrome c release as well as hippocampal ADP/ATP ratio. The results showed that MDMA caused spatial memory impairments as well as mitochondrial dysfunction as evidenced by the marked increase in hippocampal ADP/ATP ratio, ROS level, the collapse of MMP, mitochondrial swelling, and mitochondrial outer membrane damage leading to cytochrome c release from the mitochondria. The current study also found that bucladesine markedly reduced the destructive effects of MDMA. These results provide evidence of the role of the parent compound (MDMA) in MDMA-induced memory impairments through mitochondrial dysfunction. This study highlights the role of cAMP/PKA signaling in MDMA-induced memory and mitochondrial defects.

Time-course investigation of postural sway variability: Does anxiety exacerbate the sensory reweighting impairment in chronic stroke survivors?

Although anxiety is one of the most prevalent psychological disorders in stroke survivors, its effect on sensory reweighting has not yet been fully studied. The aim of this work was to investigate how anticipation of collision avoidance events affects sensory reweighting in chronic stroke survivors with low and high levels of anxiety (LA-stroke and HA-stroke, respectively), as compared with healthy controls (HC), under the condition of perturbed proprioception. Eighteen LA-stroke and 18 HA-stroke survivors, as well as 18 gender- and age-matched HC, participated in this study. Postural sway variability (i.e. Root Mean Square (RMS) of the COP velocity) was measured for a duration of 180 s under two conditions: quiet standing and standing while predicting random virtual spheres to be avoided. Proprioceptive perturbation was simulated using bilateral Achilles tendon vibration at mid duration (60 s) for both conditions. The results showed that the HC were able to timely use visual anticipation to reduce the postural sway variability induced by tendon vibration. However, marked delay in using such anticipation was observed in stroke participants, especially in the HA-stroke group, as indicated by a significant decrease in the RMS of the COP velocity late in the vibration phase. This is the first study to consider the effect of anxiety while comparing sensory reweighting between stroke and healthy participants. The results indicated that chronic stroke survivors, particularly those with HA, could not efficiently use sensory reweighting to maintain balance in sensory conflicting conditions, which may subject them to loosing balance and/or falling. These findings are critical for future assessment and planning of rehabilitation interventions and balance in chronic stroke survivors.

The effects of anxiety and external attentional focus on postural control in patients with Parkinson's disease.

BACKGROUND: Although anxiety is a common non-motor outcome of Parkinson's disease (PD) affecting 40% of patients, little attention has been paid so far to its effects on balance impairment and postural control. Improvement of postural control through focusing on the environment (i.e. external focus) has been reported, but the role of anxiety, as a confounding variable, remains unclear. OBJECTIVES: This study aimed to investigate the influence of anxiety and attentional focus instruction on the standing postural control of PD patients. METHODS: Thirty-four patients with PD (17 with high anxiety (HA-PD) and 17 with low anxiety (LA-PD)), as well as 17 gender- and age-matched healthy control subjects (HC) participated in the study. Postural control was evaluated using a combination of two levels of postural difficulty (standing on a rigid force plate surface with open eyes (RO) and standing on a foam surface with open eyes (FO)), as well as three attentional focus instructions (internal, external and no focus). RESULTS: Only the HA-PD group demonstrated significant postural control impairment as compared to the control, as indicated by significantly greater postural sway measures. Moreover, external focus significantly reduced postural sway in all participants especially during the FO condition. CONCLUSION: The results of the current study provide evidence that anxiety influences balance control and postural stability in patients with PD, particularly those with high levels of anxiety. The results also confirmed that external focus is a potential strategy that significantly improves the postural control of these patients. Further investigation of clinical applicability is warranted towards developing effective therapeutic and rehabilitative treatment plans.

Mitochondrial impairments contribute to spatial learning and memory dysfunction induced by chronic tramadol administration in rat: Protective effect of physical exercise.

Despite the worldwide use of tramadol, few studies have been conducted about its effects on memory and mitochondrial function, and controversial results have been reported. Recently, there has been an increasing interest in physical exercise as a protective approach to neuronal and cognitive impairments. Therefore, the aim of this study was to investigate the effects of physical exercise on spatial learning and memory and brain mitochondrial function in tramadol-treated rats. After completion of 2-week (short-term) and 4-week (long-term) treadmill exercise regimens, male Wistar rats received tramadol (20, 40, 80mg/kg/day) intraperitoneally for 30days. Then spatial learning and memory was assessed by Morris water maze test (MWM). Moreover, brain mitochondrial function was evaluated by determination of mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release from mitochondria. Chronic administration of tramadol impaired spatial learning and memory as well as brain mitochondrial function as indicated by increased ROS level, MMP collapse, increased mitochondrial swelling and cytochrome c release from mitochondria. Conversely, treadmill exercise significantly attenuated the impairments of spatial learning and memory and brain mitochondrial dysfunction induced by tramadol. The results revealed that chronic tramadol treatment caused memory impairments through induction of brain mitochondrial dysfunction. Furthermore, pre-exposure to physical exercise markedly mitigated these impairments through its positive effects on brain mitochondrial function.

The effect of arsenite on spatial learning: Involvement of autophagy and apoptosis.

Spatial learning plays a major role in one's information recording. Arsenic is one of ubiquitous environmental toxins with known neurological effects. However, studies investigating the effects of arsenic on spatial learning and related mechanisms are limited. This study was planned toexaminethe effects of bilateral intra-hippocampal infusion of different concentrations of sodium arsenite (5, 10 and 100nM, 5µl/side) on spatial learning in Wistar rats. Moreover, we evaluated levels of LC3-II, Atg7 and Atg12 as reliable biomarkers of autophagy and caspase-3 and Bax/Bcl-2 ratio as indicators of apoptosis in the hippocampus. Interestingly, low concentrations of sodium arsenite (5 and 10nM) significantly increased spatial acquisition but pre-training administration of sodium arsenite100nM did not significantly alter spatial learning. LC3-II levels were significantly increased in groups treated with sodium arsenite 5 and 10nM and decreased in the group receiving arsenite 100nM compared to the control group. Atg7 and Atg12 levels were obviously higher in all groups treated with sodium arsenite compared to control. However, caspase-3 cleavage and Bax/Bcl-2 ratio were notably greater in 100nM, and lesser in 5nM arsenite group in comparison with control animals. The results of this study showed that the low concentrations of sodium arsenite could facilitate spatial learning. This facilitation could be attributed to neuronal autophagy induced by low concentrations of sodium arsenite. These findings may help to clarify the regulatory pathways for apoptosis and autophagy balance due to sodium arsenite.

Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function.

Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100µg/kg/side) and H-89(10µM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders.

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function.

BDNF modifies hippocampal KCC2 and NKCC1 expression in a temporal lobe epilepsy model.

Excitatory GABA actions, induced by altered expression of chloride transporters (KCC2/NKCC1), can contribute to seizure generation in temporal lobe epilepsy. In the present study, we evaluated whether BDNF administration can affect KCC2/NKCC1 expression, ictogenesis and behavioral alterations in this paradigm. Status epilepticus was induced in male rats with pilocarpine, followed by a treatment of either a single high dose or multiple injections of BDNF during the latent phase of temporal lobe epilepsy. Chloride transporters expression, spontaneous recurrent seizures, and hyperexcitability post-seizural behaviors were evaluated after treatment. NKCC1 protein expression was markedly upregulated, whereas that of KCC2 was significantly downregulated in epileptic hippocampi compared to intact controls. Application of BDNF (both single high dose and multiple injections) increased KCC2 expression in epileptic hippocampi, while NKCC1 expression was downregulated exclusively by the single high dose injection of BDNF. Development of spontaneous recurrent seizures was delayed but not prevented by the treatment, and hyperexcitability behaviors were ameliorated for a short period of time. To prevent GABA-A mediated depolarization and design appropriate treatment strategies for temporal lobe epilepsy, chloride transporters can be considered as a target. Future studies are warranted to investigate any possible therapeutic effects of BDNF via altering chloride transporters expression.