The P2X7 receptor in activated microglia promotes depression- and anxiety-like behaviors in lithium -pilocarpine induced epileptic rats.

Depressive and anxious behaviors are the most common psychiatric symptoms of epilepsy, and may aggravate the epileptic condition and affect the patient's quality of life. Accumulating data obtained from both experimental animal models and patients have convincingly shown a critical role of P2X7 receptor (P2X7R) during depression and anxiety. Our study showed for the first time that the P2X7R is involved in promoting depression- and anxiety-like behaviors in lithium pilocarpine-induced epileptic rats. More importantly, direct anti-depressive and anti-anxiety effects were produced by the P2X7R antagonist Brilliant Blue G (BBG) is in this study, and the effect was similar to that of the classic anti-depressant and anti-anxiety drug fluoxetine. We also found that BBG did not affect the development of spontaneous recurrent seizures (SRS) and had a neuroprotective effect via inhibition of microglial activation after status epilepticus (SE). Thus, our data provide evidence that the P2X7R in activated microglia promotes depression- and anxiety-like behaviors in lithium-pilocarpine induced epileptic rats. Since previous studies have indicated that some anti-depression and anti-anxiety drugs may exacerbate seizures, our data support that the P2X7R is a promising therapeutic target for epilepsy associated with depression and anxiety.

The Safety and Efficiency of Tirofiban in Acute Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Limited comparative studies have reported the safety and efficacy of tirofiban in acute ischemic stroke (AIS) patients after mechanical thrombectomy (MT). Additionally, the available studies are inconsistent with each other, which makes application of tirofiban unclear in neuro-intervention. Here, we performed a comparative retrospective study to investigate whether tirofiban combined with MT improves short- and long-term prognosis in AIS patients and whether its use is associated with complications. METHOD: Retrospective data were collected for AIS patients admitted between January 2013 and January 2019 at three stroke centers. According to whether tirofiban was used during the operation, patients were divided into tirofiban group and control group. Multivariate and COX regression analyses were performed to determine the association of tirofiban treatment with safety and efficiency in subjects treated with MT. RESULT: A total of 174 patients were analyzed, of whom 89 (51.1%) were treated with tirofiban. There were no differences in the incidence of symptomatic intracerebral hemorrhage (10.2% vs. 10.6%, p=0.918), parenchymal hemorrhage type 2 (18.0% vs. 16.5%, p=0.793), and reocclusion at 24 h (3.4% vs. 10.6%, p=0.060) between the tirofiban group and control group. Multivariate regression showed that tirofiban was not associated with intracerebral hemorrhage, early neurological deterioration, neurological improvement at 7 days, functional independence at 3-month and 9-month follow-up, or death at 9-month follow-up (adjusted p > 0.05 for all). However, AIS patients treated with MT + tirofiban showed a trend towards acquiring faster functional independence, with a median time to acquire functional independence of 4.0 months compared with 6.5 months in the control group (risk ratio = 1.49, 95% confidence interval 0.98-2.27; long rank p=0.066). CONCLUSION: Tirofiban may help AIS patients given MT to gain functional independence faster, without increasing the risk of complications.

Losartan inhibits development of spontaneous recurrent seizures by preventing astrocyte activation and attenuating blood-brain barrier permeability following pilocarpine-induced status epilepticus.

Blood-brain barrier (BBB) damage and astrocyte activation are important cause of recurrent epilepsy. There is experimental evidence for increased angiotensin receptor type 1 (AT1) expression during BBB breakdown and brain injury, and that blocking the AT1 receptor (e.g., with losartan) can improve microcirculation, attenuate inflammation and oxidative stress, and exhibit neuroprotective effects. Thus, in the present study, we examined the effects of losartan on status epilepticus-induced astrocyte activation and BBB damage in the lithium-pilocarpine model of epilepsy in rats. We found that losartan treatment reduced astrocyte activation and BBB damage. However, under physiological condition, losartan have not effect on BBB permeability and astrocyte activation. Further, losartan exhibited a direct antiepileptic effect, which was mediated, at least in part by normalizing AQP4 expression after SE. As the changes of AQP4 expression were closely related to astrocyte activation and BBB permeability, the antiepileptic action of losartan likely relates to its effects on astrocyte activation and BBB permeability. Overall, these data suggest that losartan may be a useful antiepileptic agent in the clinic, either alone or in combination with other antiepileptic drugs.

Activation of PPARγ pathway enhances cellular anti-oxidant capacity to protect long-term cultured primary rat neural cells from apoptosis / 南方医科大学学报

OBJECTIVE@#To study the protective effect of enhanced peroxisome proliferator activated receptor γ (PPARγ) pathway against apoptosis of long-term cultured primary nerve cells.@*METHODS@#A natural aging model was established in primary rat nerve cells by long-term culture for 22 days. The cells were divided into control group, 0.1, 1.0, 5.0, and 10 μmol/L GW9662 intervention groups, and 0.1, 1.0, 5.0, and 10 μmol/L pioglitazone intervention groups. The cell viability was assessed using MTT assay and the cell morphological changes were observed after the treatments to determine the optimal concentrations of GW9662 and pioglitazone. Double immunofluorescence labeling and flow cytometry were used to observe the changes in the number of viable cells and cell apoptosis following the treatments; immunocytochemical staining was used to assess the changes in the anti-oxidation ability of the treated cells.@*RESULTS@#The optimal concentrations of GW9662 and pioglitazone determined based on the cell viability and morphological changes were both 1 μmol/L. Compared with the control group, GW9662 treatment significantly lowered while pioglitazone significantly increased the total cell number and nerve cell counts ( < 0.05), and nerve cells in the cell cultures maintained a constant ratio at about 80% in all the groups ( > 0.05). GW9662 significantly enhanced while pioglitazone significantly lowered the cell apoptosis rates compared with the control group ( < 0.05). GW9662 obviously lowered SOD activity and GSH content in G group ( < 0.05) and increased MDA content in the cells ( < 0.05), and pioglitazone resulted in reverse changes in SOD, GSH and MDA contents in the cells ( < 0.05).@*CONCLUSIONS@#Activation of PPARγ pathway protects long-term cultured primary nerve cells by enhancing cellular anti-oxidant capacity and reducing cell apoptosis, suggesting a potential strategy for anti-aging treatment of the nervous system through intervention of the PPARγ pathway.

Effect of the ioversol on early renal function in patients undergoing cerebral vascular intervention / 中国医师杂志

Objective To investigate the effect of different doses of ioversol on renal function,and to explore early renal injury biomarkers on contrast induced kidney injury and safe ioversol dosage.Methods A total of 158 cases (98 males and 60 females) undergoing cerebral vascular intervention (CVI) in our department was selected with age ranging from 23 to 81 years old (average age 59.70 ± 12.02).Based on ioversol dosage in surgery,patients were divided into three groups:low dose group (≤ 150 ml,n =49),middle dose group (151-200 ml,n =74),and high dose group (＞200 ml,n =35).U-κ,U-λ,urinary transferrin (UTRF),urine microalbumin (UMA),urinary immunoglobulin IgG (UIgG),urine beta2-microglobulin (Uβ2-MG),Uα1-MG,urinary N-acetyl-beta-D-glucosaminidase (UNAG),plasma cystatin C (CysC) and Scr were detected by scattering turbidimetry,immune turbidimetry and fully automatic biochemical analysis pre-surgery 24 h and post-surgery 72 h.Contrast-induced acute kidney injury (CI-AKI) was defined as laboratory increase of Scr value≥44.2 μmol/L or ≥25％ from baseline measurement at 48 hours after surgery.The relationship in ioversol dosage and various factors was assessed by Single and multiple factors binary logistic regression analysis.Results According to the criterion that Scr increase value were ≥44.2 μmol/L,of 158 cases,3 cases occurred CI-AKI,the AKI incidence was 1.90％.Based on the criterion that Scr increase value was ≥25％,33 cases occurred CI-AKI,the incidence was 20.89％.The concentration of U-κ,UTRF,Uα1-MG,UNAG and plasma CysC were significantly different in high dose group compared to low ioversol dose group (P ＜ 0.05),while the other biomarkers had no significant difference (P ＞ 0.05).Conclusions The contrast media-ioversol could lead to CI-AKI;when the dosage of ioversol was more than 200 ml one-time,the concentration of U-κ,UTRF,Uα1-MG,UNAG and plasma CysC increased significantly.U-κ,UTRF,Uα1-MG,UNAG and plasma CysC could predict the early renal injury in patients who undergoing CVI.The rise of U-κ,UTRF,Uα1-MG,UNAG and plasma CysC are related to the dosage of ioversol.Furthermore,possibility of kidney injury is significantly high when ioversol dosage is more than 200 ml one-time.

Changes in CD40 expression in the pallium and hippocampus in epileptic rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the expression of inflammatory molecule CD40 in the pallium and hippocampus of rats after status epilepticus (SE).
@*METHODS@#The expression of CD40 in the pallium, the different areas of hippocampus and the different cells from the lithium-pilocarpine epileptic rats at different time points were examined by immunohistochemistry and double-immunofluorescent labeling.
@*RESULTS@#After SE, CD40 expression was obviously inhibited, especially in hippocampus. CD40 was mainly expressed in the activated microglia. CD40 positive cells reached a peak at the 3rd day and returned to a slightly higher level at the 7th day after SE compared with the level before SE.
@*CONCLUSION@#Elevation of CD40 expression in the activated microglia can promote inflammatory injury of rat's hippocampus, suggesting that CD40 induced-signal pathway is involved in inflammatory injury in the hippocampus after SE.

Expression of vascular endothelial growth factor and microvessel density in different brain regions in aged rats / 中南大学学报(医学版)

Objective:To observe the distribution of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in different brain regions in aged rats and determine the role of VEGF and MVD in the aging process of the nervous system. Methods:We observed the expression of VEGF and MVD in different parts of rat brain in the 3- month group and 30-month group with immunohistochemical technique. Results:Compared with the 3-month group, the 30-month group showed fewer VEGF-positive cells and MVD in the brain (P<0.01), and the number varied signiifcantly in different brain regions(P<0.01). The motor cortex region contained more VEGF-positive cells and MVD than the hippocampus and cerebellum. Conclusion:VEGF-positive cells and MVD are decreased in every brain region of aged rats, and the motor cortex region contains more positive cells, suggesting exogenous VEGF may enhance the formation of microvessels and delay the aging of the nervous system.

The PPARγ agonist rosiglitazone prevents neuronal loss and attenuates development of spontaneous recurrent seizures through BDNF/TrkB signaling following pilocarpine-induced status epilepticus.

Hippocampal neuronal loss plays an important role in epileptogenesis, and it is considered a trigger of repeated spontaneous recurrent seizures (SRS). The BDNF/TrkB signaling pathway regulates neuronal plasticity in the CNS, and promotes epileptogenesis. Previous studies have shown that Peroxisome proliferator-activated receptor gamma (PPARγ) agonists exert neuroprotective effects by inhibiting oxidative stress and inflammation in epilepsy. In the present study, the PPARγ agonist rosiglitazone inhibited increases in BDNF and TrkB after status epilepticus (SE), and also prevented hippocampal neuronal loss. More importantly, our study showed that rosiglitazone suppressed SRS. However, the effects of rosiglitazone were significantly reversed by cotreatment with K252a, an antagonist of TrkB. Additionally, rosiglitazone did not affect the development and severity of SE. Thus, our data provide evidence that rosiglitazone exerts neuroprotective and antiepileptic effects involve BDNF/TrkB signaling. Our study also offers new perspectives for the treatment of epilepsy.

Effect of erythropoietin on activities of antioxidant enzymes in the brain tissue of aged rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of erythropoietin (EPO) on the activities of antioxidant enzymes, namely catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissues of aged rats.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into normal control, aging model, and recombinant human erythropoietin (rhEPO) treatment groups (n=10). Morris water maze was used to compare the behavioral indexes. The rats were then sacrificed to observe Nissl bodies in the hippocampal neurons with Nissl staining and test the activities of CAT and GSH-Px in the brain tissues.</p><p><b>RESULTS</b>Compared with the control group, the aging rats showed significantly deteriorated learning and memory abilities (P<0.05), which were improved obviously by rhEPO treatment (P<0.05). The number of Nissl bodies in the neurons was reduced in the aging rats compared with that in the control group, and rhEPO treatment increased the number of Nissle bodies but failed to restore the control level. The aging rats also showed significantly lowered activities of CAT and GSH-Px in the brain tissue (P<0.05), which were increased significantly after rhEPO treatment (P<0.05).</p><p><b>CONCLUSION</b>EPO can enhance the activities of the antioxidant enzymes in the brain tissues of aged rats to increase the antioxidant capacity and produces an anti-aging effect.</p>

The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus.

Epilepsy is commonly associated with cognitive impairment. Astrocyte activation and oxidative stress occur following seizures, and play a role in the pathological injury of epilepsy with cognitive impairment. The peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to exhibit neuroprotective and antioxidative effects in CNS diseases. Thus, we hypothesized that rosiglitazone, a PPARγ agonist, would prevent cognitive impairment by inhibiting astrocyte activation and regulating glutathione (GSH) homeostasis after status epilepticus (SE). Using a lithium pilocarpine-induced SE model, we found that rosiglitazone significantly prevented cognitive impairment induced by SE, and potently inhibited astrocyte activation with maintenance of GSH homeostasis in the hippocampus after SE. These protective effects were significantly reversed by co-treatment with the PPARγ antagonist T0070907. These data suggest that rosiglitazone can improve cognitive impairment, and inhibit astrocyte activation and oxidative damage following SE. Rosiglitazone may be a promising agent for treatment of epilepsy involving SE-induced cognitive impairment.

Changes of serum creatase and its clinical significance in patients with periodic paralysis / 临床神经病学杂志

Objective To study the changes of serum creatase and its clinical significance in patients with periodic paralysis.Methods The serum creatine phosphatase (CPK),lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured by means of speed rate method in 103 patients of periodic paralysis and 35 healthy persons as the control group. The relationship between increased serum creatase levels and the clinic findings was analyzed.Results Compared with the controls, all kinds of serum creatase levels in the patients elevated in different levels, and the differences were significant (all P

The dynamic change and its clinical significance of serum neuron-specific enolase in the patients with cerebral stroke / 临床神经病学杂志

Objective To study the value of the neuron-specific enolase(NSE) in the serum of patients with cerebral stroke in diagnosis, seriousness and evaluation of prognosis. Methods The levels of NSE in the serum of 77 patients with cerebral stroke(36 cases with hemorrhage, 41 cases with infarction) were measured by radio-immunoassay (RIA)method.Results The serum leves of NSE both in cerebral infarction and cerebral hemorrhage patients were obviously higher than those of the control group( P 0.05). In the first week there was a positive correlation between NSE serum level and neurological deficit scores,the volume of haemorrhage, the volume of infarction( P 0.05) . Conclusion The NSE level in serum may be served as a objective index of seriousness and early diagnosis in stroke, but no helpful in differential diagnosis and evaluation of prognosis.