RESUMEN
OBJECTIVE: To investigate the damage within the ventroposterior nucleus (VPN) of the thalamus after focal cortical infarction and its mechanism, and explore the effect of ebselen on the oxidative damage after cerebral cortex infarction in hypertensive rats. METHODS: Middle cerebral artery occlusion (MCAO) was induced in stroke-prone renovascular hypertensive rats (RHRSP), and the rats were divided into four groups by table of random number: sham operation group, model group, vehicle group and ebselen group, each group consisted of 8 rats. In animals subjected to sham surgery the middle cerebral artery was exposed only. Ebselen (5 ml/kg) or vehicle (a mixed solvent consisting of 0.5% carboxymethyl cellulose and 0.02% Tween 20, 5 ml/kg) was given by gastric gavage starting 24 hours after cerebral cortical infarction. Two weeks after the MCAO, the rats were sacrificed, and VPN from each group was sectioned and stained with hematoxylin-eosin (HE), and apurinic/apyrimidinic endonuclease (APE) and Escherichia coli MutY DNA glycosylase (MYH) were determined by immunohistochemistry. RESULTS: HE staining showed that ebselen ameliorated the VPN damage induced by ischemia. Immunohistochemical imaging analysis revealed a distinct nuclear staining of APE and nuclear and cytoplasm distribution of MYH in the entire region of the VPN. Compared with sham operation group, the number of APE and MYH positive cells decreased in model group and vehicle group (APE: 57.0±14.7, 49.4±12.5 vs. 101.0±13.6, MYH: 15.0±4.7, 10.4±2.5 vs. 56.0±13.2, all P<0.05). Compared with model group and vehicle group, the number of APE and MYH positive cells increased significantly in ebselen group (APE: 72.2±7.6 vs. 57.0±14.7, 49.4±12.5, MYH: 32.2±7.6 vs. 15.0±4.7, 10.4±2.5, all P<0.05); the difference of the number of APE and MYH positive cells between model group and vehicle group showed no statistical significance. CONCLUSION: After 2 weeks of MCAO, there is a marked decrease of APE and MYH in VPN; ebselen can obviously increase the level of APE and MYH, and ebselen may protect the VPN of the thalamus from damage after focal cortical infarction in rats.
Asunto(s)
Corteza Cerebral/metabolismo , Infarto Cerebral/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Tálamo/metabolismo , Animales , Corteza Cerebral/patología , Infarto Cerebral/patología , Hipertensión , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the approach of basic fibroblast growth factor(bFGF) entering inner ear, as well as its the protective mechanism to inner ear and nerve tissue in pathological situation. METHODS: 125I-bFGF was injected into guinea pigs body via the lateral ventricle and muscle under physical situation as well as pathological situation. Then the per minute gamma-radioactive in blood, liver, thyroid gland, brain, cochlear and perilymph fluid was counted, and the distribution and metabolism of bFGF in the inner ear and autoradiography of the cochlea were also observed. RESULTS: Gamma-radioactive cpm of blood and liver increased significantly, while it did not change in brain, cochlea and perilymph after 125I-bFGF intramuscular injections. Gamma-radioactive cpm in blood, liver, brain, perilymph and cochlea had increased and autoradiography granules was found in the cochlea in 30 min after 125I-bFGF injected into CSF. In brain, perilymph and cochlea, a maximal value of gamma-radioactive cpm was obtained between 2 h and 4 h, while that in 8 h decreased significantly. Autoradiography granules still were seen in 8 h. gamma-radioactive cpm in 12 h was still higher than that in control group, but autoradiography granules can't be seen. The result in 24 h was similar to that in control group. The time course of cpm in the blood, cochlea and perilymph always parallel changed. CONCLUSIONS: bFGF has some difficulties in getting across blood-labyrinth barrier (BLB) and blood-brain barrier (BBB) under physical and pathological situation, such as acute anoxia, aminoglycoside-induced deafness. bFGF can reach inner ear, perilymph fluid, brain tissue and blood rapidly when it is injected into CSF and excreted slowly in those tissues. Permeability of BBB and BLB to bFGF is similar and has orientation.