Causative factor to cerebral inflammation in a transgenic mouse model of Alzheimer's disease / 中国综合临床

Objective To observe the changes of cerebral inflammation-related markers in brain of a transgenic mouse model of Alzheimer's disease (AD) ,and to determine the causative factor to the development of cerebral inflammation in AD. Methods 3- and 12-month-old β-amyloid protein precursor ( APP)/presenilin (PSI) transgenic mice and age-matched wild-type mice (WT) were used in the study. The changes of amyloid plaques, inflammatory factors ( interleukin 1β ( IL-1β ); interleukin 6( IL-6 ); tumor necrosis factor α (TNFα) ;prostaglandin E2 (PGE2)) in the brains among these mice were measured by immunohistochemistry and ELISA. Results Immunohistochemical analysis revealed that no amyloid plaques and activated astrocytes as well as microglia were observed in the 3-month-old APP/PS1 mice. There were no significant differences in the levels of inflammatory factors (IL-1β, IL-6 ,TNFα,and PGE2) between the 3-month-old APP/PS1 and WT mice ( Ps ＞ 0. 05 ). However, abundant amyloid plaques accompanied by a remarkable increase of activated astrocytes and microglia were found in the brain of the 12-month-old APP/PS1 mice. The levels of inflammatory factors (IL-1β,IL-6,TNFα, and PGE2 ) were significantly increased in the 12-month-old APP/PS1 mice ([56. 02 ±9. 04] ng/g, [8. 66 ±0.83] ng/g, [97.48 ±26.58] ng/g, [72. 18 ±21.01] ng/g) than in the WT mice ([29. 18 ± 6. 03] ng/g, [7. 73 ± 0. 74] ng/g, [61.98 ±11.11] ng/g, [37. 23 ± 10. 96] ng/g) and the 3-month-old APP/PS1 mice ( [30. 05 ± 3.53] ng/g, [7.43 ± 1.17] ng/g, [59.34 ± 10. 07] ng/g, [42. 56 ±5.93] ng/g) (P＜0.05,or P＜0.01,respectively). Conclusion This study demonstrates that the APP/PS1mice did not show cerebral inflammation before the appearance of amyloid plaques, and exhibited remarkable inflammation after amyloid plaque deposition. These findings suggest that the induction of cerebral inflammation is tightly associated with amyloid plaque formation, and deposition of amyloid-beta protein (Aβ) may be the direct causative factor to the development of cerebral inflammation in AD.

Relationship between early memory impairment and oxidative stress in transgenic mouse model of Alzheimer's disease / 中国综合临床

Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P ＜0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P ＜0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P ＜0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P ＜ 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P ＜ 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P ＜ 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P ＜ 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP/PS1 mice, suggesting that protein carbonylation caused by oxidative stress might play an important role in the development of memory impairment in the early stage of Alzheimer's disease.

Clinical and neuroimaging features of reversible posterior leukoencephalopathy syndrome / 中国神经精神疾病杂志

Objective To investigate the clinical and neuroimaging characteristics of patients with reversible posterior leukoencephalopathy syndrome (RPLS). Methods The etiology, clinical manifestations, neuroimaging features, treatment, and prognosis were retrospectively analyzed in 8 patients (5 males and 3 females) with RPLS. Results The causes of RPLS included systemic lupus erythematosus (2 cases) eclampsia (one case), primary hypertension (one case), fungal encephalitis (one case), multiple myeloma (one case), renal transplantation (one case), immunosuppressant (three cases), chemotherapy (one case) and antifungal agent (one case). The clinical manifestations of these patients included headaches, seizures, visual abnormalities, and consciousness or mental disorders. Magnetic resonance imaging (MRI) of the head mainly showed symmetrical abnormalities in the posterior regions of the brain, as evidenced by low or equal signal on T_1WI, and high signal on T_2WI and FLAIR images. After treatment with antihypertensive agents, dehydration therapy, and heteropathy for 2～3 weeks, the neurological deficits of the patients were almost resolved and the initial lesions disappeared completely or almost completely in all patients at the follow-up MRI. Conclusions RPLS is a clinical entity characterized by reversible white matter damage in posterior brain. Prompt diagnosis and treatment may result in reversible resolution of its clinical symptoms and neuroradiological lesions.

Clinical analysis of two patients with rhythmic movement disorder / 中华神经科杂志

Objective To investigate the clinical features and the possible pathogenesis of rhythmic movement disorder (RMD) by analyzing 2 patients with RMD and reviewing the literature. Methods By using overnight polysomnogram (PSG) and sleeping video monitoring, the movement patterns, sleep architecture, and sleep quality of 2 patients who met the RMD diagnostic criteria were examined. Results Two male patients were 15-years old. The onset age of patient 1 was 3-years old, and patient 2 was 10-years old. All abnormal movements occurred in sleep, which presented with repetitive, stereotyping and rhythmical movements. Multiple patterns of abnormal sleeping movement were observed in 2 patients: head hypsokinesis, thoracic and waist hyperextension, and pendular movement of bilateral upper extremities. In the sitting position, the patient exhibited kneeling position, and fore-and-aft or lateral rhythmical swing of the upper body accompanied with head-banging. In the prone position, the patient behaved head backward hyperextension, and horizontal and fluctuating pendular movement of the body, which was just like the auto-erotic situation. In the lateral sleep position, the patient supported their head by using the right hand accompanied with fore-and-aft pendular movement of the head and the upper body. These symptoms mentioned above emerged immediately when the patient fell asleep, and continuously existed in all sleep period including non-rapid eye movement and rapid eye movement. All of the symptoms disappeared once the patient woke. The abnormal movement frequency was 0.1-2.0 Hz. In addition, the sleep architecture and quality were severely influenced by RMD in patient 2. Clonazepam might markedly ameliorate the symptoms and sleep quality. Conclusions Multiple abnormal movement patterns may exist in the RMD patients, and these abnormal movements could last during the whole sleep period. PSG and sleeping video monitoring should be undertaken for the suspected RMD patients, which are very useful for the definite diagnosis of RMD.

Restless legs syndrome:23-cases report / 中华神经科杂志

Objective To investigate the clinical features of restless legs syndrome(RLS),its possible pathogenesis.and the effects of benserazide on the patients with RLS.Methods Twenty-three patients who met the primary diagnostic criteria of RLS were retrospectively analyzed.Results Twenty-three middle-aged or elderly patients aged 56 years in average had an average onset age of 52 years.Insomnia and daytime sleepiness were mostly common complains for these patients.Based on the diagnostic criteria of International RLS study group(IRLSSG),the average IRLSSG score was 25,and 16 cases(69%)of the patients were severe(21-30).Polysomnographic examination showed that 18 cases(78%)had periodic limb movement.in which the PLM index of 11 cases(61%)patients Was moderate(25-49).PLM-arousal index of all patients was increased.that of 16 cases(67%)patients being moderate.After treatment by levodopa/benserazide 100/25 mg at bedtime each night for 4 weeks,most of patients'subjective symptoms improved markedly.and the IRLSSG score Was obviously decreased.with an average score of 13,and 5 patients became completely normal.Among patients with periodic legs movement.the PLM index became normal in 5 patients and became mild in others.In addition.the PLM-arousal index in all patients Was markedly decreased.with that of 11 patients becoming normal.The sleep latency of 19 patients became normal.On the other hand,6 patients(26%)had transient headache,nausea,and lethargy.Conclusions Patients with discomfortable feeling of lower extremity which is mitigated after movement.and legs movement during sleep should be check up as early as possible.Benserazide may be considered as an effeetive medication for patients with RLS.