RESUMO
BACKGROUND: 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) can decrease brain temperature, which is the potential mechanism of its neuroprotection. OBJECTIVE; To investigate the effect of 8-OH-DPAT on hypoxia inducible factor 1 a in the brain tissue of rats with diffuse axonal injury, and to explore the underlying mechanism of 8-OH-DPAT exerting neuroprotection in rats of diffuse axonal injury. METHODS; The study was approved by the Laboratory Animal Ethical Committee of General Hospital of Northern Theater Command. Wistar rats were randomly assigned into four groups: Model group (n=35), constant temperature group (n=35), 8-OH-DPAT group (n-35) and normal group (n=7). Excepting the normal group, rat models of diffuse axonal injury were established according to Marmarou method. Rat models in the constant temperature and 8-OH-DPAT were intraperitoneally injected with 8-OH-DPAT, but those in the model and normal groups were intraperitoneally injected with physiological saline. The body temperature of rats in the constant temperature group was maintained at (37.0±0.5)°C using the blanket. The body temperature of rats was measured every 1 hour. Then, brain injury and hypoxia inducible factor 1a expression level were observed at 6, 12, 24, 72, and 168 hours after diffuse axonal injury in rats. RESULTS AND CONCLUSION: (1) Compared with the constant temperature and model groups, brain temperature was significantly lower in the 8-OH-DPAT group at 1 hour following modeling (P < 0.05), became lowest at 2 hours (P < 0.05), and then gradually increased. (2) Hematoxylin-eosin staining results revealed that brain injury was more serious in the model group, followed by constant temperature group, and lightest in the 8-OH-DPAT group. (3) Results of immunohistochemistry and ELISA showed that the expression level of hypoxia inducible factor 1a in the serum and brain tissue was lowest in the normal group. In the 8-OH-DPAT group, the expression level of hypoxia inducible factor 1a was increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. Compared with the model group, the expression level of hypoxia inducible factor 1a in serum and brain tissue in the constant temperature and 8-OH-DPAT groups was significantly decreased (P < 0.05 or P < 0.01), especially the 8-OH-DPAT group (P < 0.01). (4) These results imply that 8-OH-DPAT decreases hypoxia inducible factor 1a expression in brain tissue of diffuse axonal injury rats by reducing brain temperature, alleviates the degree of nerve injury, and exerts a neuroprotective effect.
RESUMO
Objective To investigate cellular and behavioural effects of 5-HT1A receptor agonist 8- OH-DPAT in a rat model of levodopa-induced motor complications.Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle(MFB).Two sets of experiments were performed.First,rats were intrapefitoneally treated with levodopa 50 mg/kg plus benserazide 12.5 mg/kg twice a day for 22 days.On day 23,rats intraperitoneally received either 8-OH- DPAT(1 mg/kg)or 8-OH-DPAT plus WAY-100635(0.1 mg/kg)or dissolvent with each levodopa dose as controls.In the second set,rats were intraperitoneally treated either with levodopa(50 mg/kg)plus 8-OH- DPAT(1 mg/kg)or levodopa 50 mg/kg plus dissolvent,administered twice daily for 22 consecutive days. Rotational duration and frequency of off period were estimated.After sacrificed,subcellualr distribution of GluR1 and GluR1Ser845 phosphorylation was observed by Western blot.Results 8-OH-DPAT,reversing the shortened rotational duration induced by levodopa,prolonged the rotational duration by 27.8%?6.1% and reduced the frequency of failures to levodopa by 7.2%?1.7%.Co-administration of WAY-100635,a 5-HT1A receptor antagonist,with 8-OH-DPAT eliminated the effect of 8-OH-DPAT on motor complications, indicating that the observed 8-OH-DPAT responses were probably mediated via the 5-HT1A autoreceptor. Moreover,8-OH-DPAT could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser845 by 22.1%?3.5%,which was closely associated with levodopa-induced motor complications. Conclusions These results suggest that pharmaceuticals stimulating 5-HT1A receptors could be useful in the treatment and prevention of the motor complications in parkinsonian patients.