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.

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.