1.Effect of perampanel on CC chemokine receptor 5 expression and hippocampal neuron injury in epileptic rats
Danrong LEI ; Jiajuan WANG ; Haibing DAI ; Yanyan WANG ; Pu LI ; Xianping JIANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(7):946-951
Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P<0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P<0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P<0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P<0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)%vs(6.36±0.31)%,P<0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.
2.Effect of perampanel on CC chemokine receptor 5 expression and hippocampal neuron injury in epileptic rats
Danrong LEI ; Jiajuan WANG ; Haibing DAI ; Yanyan WANG ; Pu LI ; Xianping JIANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(7):946-951
Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P<0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P<0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P<0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P<0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)%vs(6.36±0.31)%,P<0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.
3.The study of intracranial aneurysms screened by CTA among the population with family history of stroke
Quan LI ; Xiangjun ZENG ; Jinlong LI ; Juan TENG ; Jiajuan LI ; Huazhang SONG ; Yanhua ZHANG
Journal of Practical Radiology 2017;33(6):539-542
Objective To explore the status of intracranial aneurysms screened by CTA among the population with family history of stroke.Methods 200 patients including 108 men and 92 women in our hospital were involved,who had a family history of stroke.Head CTA examination,physical examination and laboratory tests were performed.Results 200 male and female had no statistical significance in demographic characteristics,past medical history and physical testing (P>0.05);in lifestyle,smoking and drinking prevalence among male were higher than female (P<0.05),and drug-usage rate of female were higher than male (P<0.05).27 cases (13.5 ¥)had intracranial aneurysms,including 13 male cases (12.03 %) and 14 females cases(15.22 %),and there was one occurred aneurysm rupture and subarachnoid hemorrhage,the prevalence rate of aneurysm rupture was 87%.The 27 intracranial aneurysms cases had 29 CPC aneurysms,with 2 cases had two aneurysms.The number of aneurysm diameter <3 mm were 7 (24.14%),3 7 mm diameter were 12 (41.38%),and >7 mm were 10 (34.48%).Classified by the morphology,there were 7 (24.14%) fusiform aneurysm,22 (75.86%) cystic,3 (10.34%) small drops of blood sample.Conclusion CTA is a noninvasive and effective method for intracranial aneurysm,can provide additional valuable diagnostic information particularly for emergency of aneurysm screening.

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