الملخص
The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid (RA) on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups: sham operation (sham) group, cerebral ischemia (CI) group and RA treatment (RA) group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266±0.019, 1.215±0.063 and 0.702±0.081, respectively (P<0.01). The number of Gap-43-positive nerve cells at 7th day after MCAO in sham, CI and RA group was 0, 59.08±1.76 and 76.20±3.12 per high power field, respectively (P<0.05). The number of synapses at 7th day after MCAO was 8.42±0.13, 1.74±0.37 and 5.39±0.26 per μm(2), respectively (P<0.05). It is concluded that LINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.
الملخص
The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid (RA) on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups: sham operation (sham) group, cerebral ischemia (CI) group and RA treatment (RA) group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266 ± 0.019, 1.215 ± 0.063 and 0.702 ± 0.081, respectively (P<0.01). The number of Gap-43-positive nerve cells at 7th day after MCAO in sham, CI and RA group was 0, 59.08 ± 1.76 and 76.20 ± 3.12 per high power field, respectively (P<0.05). The number of synapses at 7th day after MCAO was 8.42 ± 0.13, 1.74 ± 0.37 and 5.39 ± 0.26 per μm², respectively (P<0.05). It is concluded that LINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.
الموضوعات
Animals , Male , Rats , Blotting, Western , Brain Ischemia , Metabolism , GAP-43 Protein , Genetics , Metabolism , Gene Expression , Membrane Proteins , Genetics , Nerve Tissue Proteins , Genetics , Neurons , Metabolism , Rats, Sprague-Dawley , Tretinoin , Pharmacologyالملخص
Objective To study the neuroprotective effect and the mechanism of carbamylated erythropoietin (CEPO) on ischemic brain injury, and compare it with erythropoietin (EPO). Methods Focal cerebral ischemia/reperfusion models were induced by occlusion of the middle cerebral artery using the intraluminal filament technique. Four groups (control group, EPO 5 μg/kg treatment group, EPO 50μg/kg treatment group and CEPO 50 μg/kg treatment group) were chosen (n=6). The cerebral blood flow was monitored through a Laser-Doppler flow probe. The slices of brain tissue were stained with cresyl-violet and the cerebral volume of infarction and edema was measured by ImageJ software. The apoptotic cells were detected with TUNEL staining. The inducible NO synthase (iNOS) positive cells were observed by immunohistochemistry. Results Compared with the control group, the EPO 50 μg/kg treatment and CEPO 50 μg/kg treatment groups showed significantly decreased infarct and edema volume, and lower scores of national institutes of health stroke scale. The numbers ofiNOS positive cells in the ischemic cortex of the EPO 50 μg/kg treatment and CEPO 50 μg/kg treatment groups were statistically smaller than those of the control group (P＜0.05). The numbers of apoptotic cells in the ischemic cortex ofthe EPO 50 μg/kg treatment and CEPO 50 μg/kg treatment groups ([43.6±10.1] cells,[40.5±9.8] cells) were obviously smaller than those of the control group ([94.2±15.2] cells, P＜0.05).Conclusion Lower dose of EPO (5 μg/kg) has no brain protective effect. Treatment with CEPO 50μg/kg and EPO 50 μg/kg have equal roles in increasing the cerebral blood flow, decreasing the neurological deficit scores and volume of infarct and edema, and boosting the anti-apoptosis by means of inhibiting the expression of iNOS.