Fibroblast growth factor 2 improves cognitive function in neonatal rats with hypoxic ischaemic brain injury.

OBJECTIVE: To determine the effect of fibroblast growth factor 2 on cognitive function in neonatal rats with hypoxic-ischaemic brain injury. METHODS: The randomised controlled study was conducted from January to June 2011 at Mersin University, School of Medicine, Experimental Animals Research Laboratory and Physiology Behaviour Laboratory, Mersin, Turkey. It included 7-d-old male rats that were randomised into four groups: fibroblast growth factor 2-20, fibroblast growth factor 2-40, control and sham. All the rats, except those in the sham group, were kept in a hypoxia chamber containing 8% oxygen for 2 hours following ligation of the right carotid artery. After hypoxic-ischaemic brain injury was induced, 20 ng g-1 or 40 ng g-1 of fibroblast growth factor 2 was administered via the intraperitoneal route. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling method was used to evaluate neuronal apoptosis. The Morris water maze (MWM) test was administered to the rats at age 14 weeks. RESULTS: Of the 78 rats on the study, 18 (23%) were in the sham group, while the other three groups had 20 (25.6%) rats each. The number of apoptotic neurons in the right hemisphere in the experimental groups was significantly lower than in the control group (p=0.004 and p<0.001). The number of apoptotic neurons in the right hemisphere in the fibroblast growth factor 2-40 group was significantly lower than in the fibroblast growth factor 2-20 group (p<0.001). Moreover, fibroblast growth factor 2improved Morris water maze test cognitive performance in a dose-dependent manner. CONCLUSIONS: Fibroblast growth factor 2 treatment reduced neuronal apoptosis and improved cognitive functioning in neonatal rats with experimentally-induced hypoxic-ischaemic brain injury.

The effects of fibroblast growth factor-2 and pluripotent astrocytic stem cells on cognitive function in a rat model of neonatal hypoxic-ischemic brain injury.

OBJECTIVE: This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI). METHODS: The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats' cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months. RESULTS: PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1-4 of MWM testing (p < 0.001). On day 2-4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3-4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms. CONCLUSIONS: Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance.

Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats.

PURPOSE: Hypoxic-ischemic brain injury that occurs in the perinatal period is one of the leading causes of mental retardation, visual and auditory impairment, motor defects, epilepsy, cerebral palsy, and death in neonates. The severity of apoptosis that develops after ischemic hypoxia and reperfusion is an indication of brain injury. Thus, it may be possible to prevent or reduce injury with treatments that can be given before the reperfusion period following hypoxia and ischemia. Levetiracetam is a new-generation antiepileptic drug that has begun to be used in the treatment of epilepsy. METHODS: The present study investigated the effects of levetiracetam on neuronal apoptosis with histopathological and biochemical tests in the early period and behavioral experiments in the late period. RESULTS: This study showed histopathologically that levetiracetam reduces the number of apoptotic neurons and has a neuroprotective effect in a neonatal rat model of hypoxic-ischemic brain injury in the early period. On the other hand, we demonstrated that levetiracetam dose dependently improves behavioral performance in the late period. CONCLUSIONS: Based on these results, we believe that one mechanism of levetiracetam's neuroprotective effects is due to increases in glutathione peroxidase and superoxide dismutase enzyme levels. To the best of our knowledge, this study is the first to show the neuroprotective effects of levetiracetam in a neonatal rat model of hypoxic-ischemic brain injury using histopathological, biochemical, and late-period behavioral experiments within the same experimental group.

Resting energy expenditure in normal-weight and overweight/obese subjects was similar despite elevated sympathovagal balance.

OBJECTIVE: Alterations in the autonomic nervous system (ANS) may cause impairment in the metabolic processes that can lead to weight gain. The purpose of this study was to determine the difference between the resting energy expenditure (REE) and the resting ANS activity in overweight/obese and normal-weight healthy subjects. METHOD: Group 1 consisted of 18 subjects with BMI > 25 kg/m², and 20 subjects with BMI ranging from 20 to 25 kg/m² formed group 2. Measurements of low-frequency (LF) and high-frequency (HF) power components expressed in normalized units (LFnu, HFnu) and LF/HF ratio were assessed for analysis of heart rate variability, and simultaneously REE measurement was performed. RESULTS: The mean LFnu (27.2% increased) and the LF/HF were higher and the mean HFnu was lower (29.9% decreased) in group 1 than in group 2 (p < 0.01). Although a statistical difference was observed in REE between groups, REE per kilogram corrected for fat-free mass (REE(FFMcorr)) was 21.47 ± 2.92 kcal/day/kg in group 1, and 21.56 ± 1.90 kcal/day/kg in group 2, and this difference was not statistically significant (p > 0.05). CONCLUSION: We concluded that REE(FFMcorr) in overweight/obese and normal-weight subjects were similar despite elevated sympathovagal balance in overweight/obese individuals, and REE(FFMcorr) should be used to avoid misestimating the REE in obese and normal-weight subjects.

Anterior cruciate ligament reconstruction improves the metabolic energy cost of level walking at customary speeds.

PURPOSE: The metabolic energy cost of walking is altered by pathological changes in gait. It is thought that anterior cruciate ligament (ACL) deficiency alters the energy requirement for level walking through its effect on gait pattern. In this study, it is hypothesised that the metabolic energy cost of walking would improve after ACL reconstruction. METHODS: Eight patients who were undergoing ACL reconstruction for an isolated rupture were included in this prospective study. Clinical examinations, Lysholm scores and metabolic tests were performed preoperatively and at 3, 6 and 12 months after ACL reconstruction using autologous quadruple hamstring tendons. For the metabolic evaluation, net oxygen cost was calculated while walking on a treadmill at 50-, 70- and 90-m/min velocities. A two-way factorial ANOVA was performed in order to evaluate the primary effects and interactions of the time point and velocity variables on net oxygen cost. RESULTS: All patients had positive Lachman and anterior drawer tests preoperatively that became negative postoperatively and remained negative until the last follow-up point. The mean preoperative Lysholm score was 66, whereas the mean postoperative follow-up scores were 85, 91 and 94, respectively. The interaction between follow-up time point and velocity was not significant. Regardless of the selected velocity, the net oxygen cost was lower than that at preoperative levels at each postoperative time point (p < 0.05). CONCLUSION: The results of the present study indicate that the energy cost of level walking in chronic ACL-deficient patients improves after ACL reconstruction. Cause-effect-based studies with correlation evaluations that compare kinetic, kinematic and electromyographic data and metabolic cost calculations should facilitate more accurate analyses. LEVEL OF EVIDENCE: Therapeutic study, Level 4.

Determination of preferred walking speed on treadmill may lead to high oxygen cost on treadmill walking.

The energy consumption of walking relates to the intensity of physical effort and can be affected by the alterations in walking speed. Therefore, walking speed can be accepted as a crucial, determinant of energy consumption measurement for a walking test. We aimed to investigate the differences in preferred walking speed (PWS) determined both on overground and on a treadmill and, to measure walking energy expenditure and spatio-temporal parameters of gait on a treadmill at both, speeds. Participants (n=26) walked on a treadmill at two pre-determined speeds for 7 min while, indirect calorimetry measurements were being performed. Spatio-temporal parameters were collected, by video-taping during each walking session on a treadmill. The average overground preferred walking speed (O-PWS) was 85.96+/-12.82 m/min and the average treadmill preferred walking speed (T-PWS), was 71.15+/-13.85 m/min. Although T-PWS was lower, oxygen cost was statistically higher when, treadmill walking at T-PWS (0.158+/-0.02 ml/kg/m) than when the treadmill walking at O-PWS, (0.1480+/-0.02 ml/kg/m). Cadence (127+/-9.13 steps/min), stride (134.02+/-14.09 cm) and step length (67.02+/-6.90 cm) on the treadmill walking at O-PWS were significantly higher than cadence (119+/-10 steps/min), stride (117.96+/-14.38 cm) and step length (59.13+/-7.02 cm) on the treadmill walking at TPWS. In conclusion, walking on treadmill using O-PWS is more efficient than walking on treadmill using TPWS, in walking tests. Since using T-PWS for treadmill walking tests overestimates the oxygen cost of walking, O-PWS should be used for oxygen consumption measurement during treadmill walking tests.

DRD4 and DAT1 polymorphisms modulate human gamma band responses.

Gamma oscillations (30-80 Hz) have been demonstrated to be important for perceptual and cognitive processes. Animal and in vitro studies have revealed possible underlying generation mechanisms of the gamma rhythm. However, little is known about the neurochemical modulation of these oscillations during human cognition. Schizophrenia and Attention Deficit Hyperactivity Disorder, which lead to failure of attentional modulation and working memory, introduce significant changes in gamma responses and have significant associations with genetic polymorphisms of dopamine receptor D4 (DRD4), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT). Therefore, the presence of direct relations between these polymorphisms and gamma oscillations was investigated in human subjects using an auditory target detection paradigm. The 7-repeat isoform of the DRD4 polymorphism that produces a subsensitive variant of the D4 receptor enhanced the auditory evoked and induced gamma responses to both standard and target stimuli. The 10/10 genotype of the DAT1 polymorphism, which reduces DAT expression and hence yields an increase in extracellular dopamine, specifically enhanced evoked gamma responses to target stimuli. The COMT polymorphism did not significantly change gamma responses. It seems plausible to assume that the modulation pattern of the evoked gamma response by DRD4 polymorphism relates to reduced inhibition via the D4 receptor, whereas the DAT1 effect is related to the target detection mechanism probably mediated by the D1 receptor.

Involvement of rho kinase in the ouabain-induced contractions of the rat renal arteries.

Agonist and depolarization-induced vascular smooth muscle contractions include the activation of rho/rho kinase pathway. However, there are no reports addressing the question whether this pathway is involved in ouabain-induced vascular smooth muscle contractions. Therefore, in this study, the possible participation of the rho/rho kinase pathway in ouabain-induced contractions was evaluated in rat renal arteries. Effects of rho kinase inhibitors (fasudil and Y-27632) on ouabain-induced contractions, and phosphorylation of myosin binding subunits (MYPT/MBS85) of myosin phosphatase were determined using isolated tissue and Western blot experiments, respectively. Fasudil and Y-27632 inhibited ouabain-induced contractions in a concentration-dependent manner. The phosphorylation of MYPT was not altered by ouabain. However, ouabain significantly increased MBS85 phosphorylation of myosin phosphatase. The phosphorylation of both subunits of myosin phosphatase was inhibited by Y-27632. These results indicate that activation of rho kinase and the subsequent phosphorylation of MBS85 are involved in ouabain-induced contraction of rat renal arteries. This mechanism may be important in essential hypertension with elevated endogenous ouabain levels.

Alpha rhythm of the EEG modulates visual detection performance in humans.

The effects of the changes in the frequency spectrum of the electroencephalogram (EEG) on the perception of near-threshold visual stimuli and on the event-related potentials (ERPs) produced by these stimuli were investigated on 12 healthy volunteers. The stimulus intensity, at which each subject could detect 50% of the presented stimuli, was defined as the sensory threshold for that subject. Single ERP trials were separated into two groups: trials with detected and undetected stimuli. The ERPs and the average power spectra of the 1 s prestimulus periods were computed for both conditions. P300 amplitudes of the ERPs, and total power and relative band powers of the delta (0.5-4 Hz), theta (4-7.5 Hz), alpha (7.5-13 Hz), beta (13-30 Hz), and gamma (30-70 Hz) frequency bands of the prestimulus power spectra were measured. Between the two conditions, a specific difference was observed in the relative power of the alpha band, which was significantly lower before detected stimuli (p < 0.01) in line with significantly higher amplitudes of the ERPs (p < 0.001). These results show that short-lasting changes in brain's excitability state are reflected the relative alpha power of the EEG, which may explain significant variability in perceptual processes and ERP generation especially at boundary conditions such as sensory threshold.