OBJECTIVE:To determine whether retinal thinning in neuronal intranuclear inclusion disease (NIID) is associated with multilevel abnormalities across the visual system and with clinical severity. METHODS:Forty patients with NIID and 40 healthy controls underwent optical coherence tomography to measure peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thickness. Among patients with NIID, 37 underwent structural MRI for quantification of visual-region volumes and 30 underwent resting-state functional MRI for graph-theoretical assessment of visual-network topology. Cognitive function and activities of daily living were evaluated in the NIID cohort. Partial correlation and exploratory mediation analyses were used to examine associations among retinal, neuroimaging, and clinical measures. RESULTS:Patients with NIID showed diffuse thinning of the RNFL and GCC relative to controls, with mean GCC showing the best discrimination between groups. Thinner retinal measures were associated with poorer cognition, worse daily function, and lower mean cortical thickness. Structural MRI identified volume abnormalities in selected visual-system regions, particularly the lateral geniculate nucleus, early visual cortex, and dorsal/parietal regions, and retinal thickness correlated positively with the volumes of several visual regions. Poorer daily function was associated with a lower clustering coefficient of the visual network. Left V3d, the dorsal part of area V3 in the occipital visual cortex, partially mediated the association between retinal thinning and functional impairment. CONCLUSIONS:These findings support coordinated retina-brain involvement in NIID across retinal, structural, and network levels, and identify OCT-derived RNFL and GCC thickness as accessible, noninvasive candidate biomarkers of disease severity.

Cerebrospinal fluid (CSF) biomarkers are used to identify or detect the condition of multiple neurodegenerative diseases, even psychiatric disorders. However, discordant results between observational studies failed to meet the expectations of identifying neurodegenerative diseases and psychiatric disorders. We conducted this systematic review and network meta-analyses to investigate the CSF biomarkers in neurodegenerative diseases and psychiatric disorders, which contribute to the diagnosis of these diseases. Studies before September 2023 were searched based on databases. We included observational studies that compared the CSF levels of these biomarkers (Aβ1–​42, tau, p-tau181, and α-synuclein) between healthy controls, neurodegenerative diseases, and psychiatric disorders. We conducted traditional pairwise analysis and network meta-analysis to evaluate the evidence concerning these CSF biomarkers between these neurodegenerative diseases and psychiatric disorders. This network meta-analysis included 117 studies with 25,210 patients to investigate the CSF biomarkers in multiple neurodegenerative diseases and psychiatric disorders (primarily depression, bipolar disorder, and schizophrenia). For CSF Aβ1–​42 levels, there were no statistically significant differences between these groups in network analysis. Regarding CSF t-tau and p-tau181 levels, statistical significance was observed in comparing Alzheimer’s disease (AD) and other diseases, e.g., amyotrophic lateral sclerosis (ALS). Regarding CSF α-synuclein levels, statistical significance was observed in several comparisons, e.g., AD vs. ALS. Conclusively, we identified that CSF Aβ1–​42, t-tau, and p-tau181 might be promising markers distinguishing AD from other neurodegenerative diseases and cognitive impairment. It is conflicting that CSF α-synuclein acts as a marker for diagnosing neurodegenerative diseases and predicts the presence of psychiatric disorders.

ObjectiveTo summarize the clinical characteristics, antibody spectrum and neuroelectrophysiological features of autoimmune nodopathy(AN), and to explore the phenotypic differences among different antibody-positive subgroups.MethodsThe clinical and electrophysiological data of patients definitely diagnosed with AN in Beijing Tiantan Hospital, Capital Medical University, from October 2018 to January 2026 were retrospectively analyzed.ResultsA total of 33 patients with AN were included. Antibody examination results showed that, anti-neurofascin(NF)155 antibody was the most prevalent, detected in 17 patients(51.50%), followed by anti-contactin-1(CNTN1) antibody in 8 patients(24.24%). Anti-NF186 antibody(4 cases, 12.12%), anti-contactin-associated protein 1(Caspr1) antibody(2 cases, 6.06%) and dual-target antibody positivity(2 cases, 6.06%) were relatively uncommon. The main clinical manifestations of AN patients included symmetric distal paresthesia of the extremities(32 cases, 96.97%), limb weakness(31 cases, 93.93%) and sensory ataxia(25 cases, 75.76%). Different antibody-positive subgroups presented distinct phenotypic features: patients with positive anti-NF155 antibody had a relatively younger age of onset, chronic onset and a high incidence of tremor, which was dominated by immunoglobulin(Ig)G4 subclass antibodies; patients with positive anti-CNTN1 antibody had a relatively advanced age of onset, mostly presented with acute or subacute onset, and were prone to complicated nephrotic syndrome; patients with positive anti-NF186 antibody had relatively mild nerve conduction damage; patients with anti-Caspr1 antibody manifested acute or subacute onset, with relatively elevated cerebrospinal fluid protein level and 24-h intrathecal IgG synthesis rate. The prominent neuroelectrophysiological manifestations of AN included decreased motor and sensory nerve conduction velocities, prolonged distal latency, frequent non-compressive conduction block and abnormal temporal dispersion. Definite sensory nerve action potentials could not be elicited in more than half of the patients.ConclusionsPatients with AN show high heterogeneity in clinical and neuroelectrophysiological characteristics, and different antibody-positive subgroups correspond to specific clinical and neuroelectrophysiological phenotypes.

Objective Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort. Methods Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders. Results A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late‐onset (≥50 years) and 85 (42.1%) as early‐onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late‐onset in our cohort. Thirty‐nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring‐parent pairs was different, and mother‐son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring ( p < 0.001). Interpretation This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender‐linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025

PNPLA8 is a gene that causes an autosomal recessive mitochondrial disease characterised by microcephaly and intractable epilepsy in infants and cerebellar ataxia and limb weakness in adults. Herein, we report the clinical, muscle pathology, and brain imaging features of an adult patient with new variants of PNPLA8. A 27-year-old Chinese woman presented with abnormal gait at age 11, remained amenorrhoeic with an infantile uterus at age 17, and presented with head and limb tremors at age 21. The results of brain magnetic resonance imaging suggested mild cerebellar atrophy. Whole-exome sequencing was performed, and mitochondrial and spinal cerebellar ataxia genes were screened. In addition, a biceps muscle biopsy was performed. Furthermore, a comprehensive literature search was conducted, and all patients with detailed clinical and genetic data up to October 2024 were included in the analysis. The patient's genetic screening revealed compound heterozygous variants c.1777T > G (p.Tyr593Asp) and c.1515-1516delTT (p.Tyr506Serfs*27) of PNPLA8 inherited from her parents. Her muscle biopsy showed mild myopathic changes on light microscopy and mitochondrial inclusions on electron microscopy. A total of 25 patients from 21 families were reviewed. Age of onset is a very important factor in terms of patient clinical phenotype and prognosis of PNPLA8-related disorders. It has been observed that adult females with PNPLA8 variants may present with primary ovarian dysfunction. The presence of mitochondrial inclusion bodies may serve as a pathological hallmark, extending the existing spectrum of the clinical phenotypes and pathogenic variants of PNPLA8.

Background and Objectives Neuronal intranuclear inclusion body disease (NIID) is a neurodegenerative disease with highly heterogeneous clinical manifestations. The present study aimed to characterize clinical features and propose a classification system based on a large cohort of NIID in China. Methods The Chinese NIID registry was launched from 2017, and participants' demographics and clinical features were recorded. Brain MRI, skin pathologies, and the number of GGC repeat expansions in the 5′ untranslated region of the NOTCH2NLC gene were evaluated in all patients. Results In total, 223 patients (64.6% female) were recruited; the mean (SD) onset age was 56.7 (10.3) years. The most common manifestations were cognitive impairment (78.5%) and autonomic dysfunction (70.9%), followed by episodic symptoms (51.1%), movement disorders (50.7%), and muscle weakness (25.6%). Imaging markers included hyperintensity signals along the corticomedullary junction on diffusion-weighted imaging (96.6%), white matter lesions (98.1%), paravermis (55.0%), and focal cortical lesions (10.1%). The median size of the expanded GGC repeats in these patients was 115 (range, 70–525), with 2 patients carrying >300 GGC repeats. A larger number of GGC repeats was associated with younger age at onset (r = −0.329, p < 0.0001). According to the proposed clinical classification based on the most prominent manifestations, the patients were designated into 5 distinct types: cognitive impairment-dominant type (34.1%, n = 76), episodic neurogenic event-dominant type (32.3%, n = 72), movement disorder-dominant type (17.5%, n = 39), autonomic dysfunction-dominant type (8.5%, n = 19), and neuromuscular disease-dominant type (7.6%, n = 17). Notably, 32.3% of the episodic neurogenic event-dominant type of NIID has characteristic focal cortical lesions on brain MRI presenting localized cortical edema or atrophy. The mean onset age of the neuromuscular disease-dominant type was 47.2 (17.6) years, younger than the other types (p < 0.001). There was no significant difference in the sizes of GGC repeats among the patients in the 5 types (p = 0.547, Kruskal-Wallis test). Discussion This observational study of NIID establishes an overall picture of the disease regarding clinical, imaging, and genetic characteristics. The proposed clinical classification of NIID based on the most prominent manifestation divides patients into 5 types.

Background To investigate the risk factors for delayed neurocognitive recovery in elderly patients undergoing thoracic surgery. Methods A total of 215 elderly patients who underwent thoracic surgery between May 2022 and October 2022 were recruited in this prospective observational study. Cognitive function was tested by MoCA tests that were performed by the same trained physician before surgery, on postoperative day 4 (POD4), and on postoperative day 30 (POD30). Univariate and multivariate logistic regression models were used to analyze the risk factors for DNR. Results A total of 154 patients (55.8% men) with an average age of 67.99 ± 3.88 years were finally included. Patients had an average preoperative MoCA score of 24.68 ± 2.75. On the 30th day after surgery, 26 (16.88%) patients had delayed postoperative cognitive recovery, and 128 (83.12%) had postoperative cognitive function recovery. Diabetes mellitus (OR = 6.508 [2.049–20.664], P = 0.001), perioperative inadvertent hypothermia (< 35℃) (OR = 5.688 [1.693–19.109], P = 0.005), history of cerebrovascular events (OR = 10.211 [2.842–36.688], P < 0.001), and VICA (sevoflurane combined with propofol anesthesia) (OR = 5.306 [1.272–22.138], P = 0.022) resulted as independent risk factors of delayed neurocognitive recovery. On the POD4, DNR was found in 61 cases (39.6%), and age ≥ 70 years (OR = 2.311 [1.096–4.876], P = 0.028) and preoperative NLR ≥ 2.5 (OR = 0.428 [0.188–0.975], P = 0.043) were identified as independent risk factors. Conclusions The risk factors for delayed neurocognitive recovery in elderly patients undergoing thoracic surgery include diabetes, perioperative inadvertent hypothermia (< 35℃), VICA (sevoflurane combined with propofol anesthesia), and history of cerebrovascular events.

Objective To investigate whether paravertebral block reduces postoperative delirium (POD)/delayed neurocognitive recovery (DNR) in adults after major surgery with general anesthesia.Methods For this systematic review and meta-analysis, we searched online databases PubMed, EMBASE, CENTRAL, and Web of Science till March 19th, 2023 to examine studies which use paravertebral block (PVB) for perioperative neurocognitive disorder. Primary and secondary outcomes were identified for the incidence of perioperative neurocognitive disorder. We did not restrict the follow-up duration of the included studies. Statistical analysis was performed to calculate mean difference (MD), Odd ratios (OR) and CI between RCTs. The quality of the evidence was assessed with the Cochrane risk of bias tool. The registration number of the study in PROSPERO is CRD42023409502. PROSPERO is an international database of prospectively registered systematic reviews. Registration provides transparency in the review process and it helps counter publication bias.Results Total 1,225 patients from 9 RCTs were analyzed. The incidence of POD [Odds Ratio (OR) = 0.48, 95% CI 0.32, 0.72; p = 0.0004; I2 = 0%] and DNR [OR = 0.32, 95% CI 0.13, 0.80; p = 0.01; I2 = 0%] were significantly reduced in PVB group. The analysis showed no significant differences in postoperative MMSE scores [MD = 0.50, 95% CI -2.14, 3.15; p = 0.71; I2 = 98%]. Paravertebral block analgesia reduces pain scores and/or opioid use after surgery. Additionally, blood pressure was significantly lower in the PVB group, intraoperatively [MD = -15.50, 95% CI -20.71, -10.28; p < 0.001; I2 = 12%] and postoperatively [MD = -5.34, 95% CI -10.65, -0.03 p = 0.05; I2 = 36%]. Finally, PVB group had significantly shorter hospital stays [MD = -0.86, 95% CI -1.13, -0.59; p < 0.001; I2 = 0%].Conclusion Paravertebral block analgesia may prevent perioperative POD/DNR in patients undergoing major surgery. Further research with large sample sizes is required to confirm its effectiveness.

Background: The full clinical spectrum of neuronal intranuclear inclusion disease (NIID) and its relationship with genotype have not been documented. We aimed to identify the clinical, neuroimaging, and genetic features of adult-onset NIID. Methods: An adult-onset NIID registry was launched in multiple centres throughout China. Clinical data, routine brain magnetic resonance imaging, and skin pathologies were evaluated. Arterial spin labelling magnetic resonance imaging and electrophysiological studies were conducted. Repeat-primed and amplicon length polymerase chain reaction were used to screen (GGC)n repeat expansions in the 5’ untranslated region of the NOTCH2NLC gene. Findings: In total, 134 adult-onset patients with NIID (66% female) from 72 clinical centres were included; 23 cases were familial. The mean age of onset was 56·9±9·4 years. The median disease duration was 4 (IQR 2–9) years. Adult-onset NIID was divided into three subtypes based on primary manifestations: dementia-dominant type (n=65), parkinsonism-dominant type (n=19), and episodic neurogenic event-dominant type (n=45). Among the patients, 90·5% presented with mild demyelinating polyneuropathy. All patients presented with high intensities along the corticomedullary junction on diffusion-weighted imaging, and 53·7% of them presented with abnormal hyperintensity in the paravermal area on T2/fluid-attenuated inversion recovery images. Cerebral blood flow in the whole brain was lower and that in globus pallidus was higher in patients with NIID than in healthy controls. (GGC) n repeat number in the 5’-untranslated region of the NOTCH2NLC gene ranged from 82 to 173 repeats. A significant inverse correlation between (GGC) n repeat number and age of onset was observed (r=–0·203, p=0·018). Interpretation: This study provides a novel classification of adult-onset NIID for clinical application. Decreased cerebral perfusion may underpin the pathogenesis of NIID and highlight the potential of perfusion modulation therapy. (GGC) n repeat number was inversely correlated with the age of onset, and the pathogenetic effect may have a cumulative effect. Funding: None Declaration of Interest: We declare no competing interests. Ethical Approval: This study was approved by the Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medical University, and adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all individuals or their authorised surrogates at enrolment.

Introduction Large artery intracranial occlusive disease including middle cerebral artery (MCA) is a major contributor to the incidence of stroke in China. The data on the prognosis of symptomatic atherosclerotic MCA occlusions (MCAO) are limited. We aimed to investigate the related factors of unfavorable outcomes in patients with stroke associated with MCAO. Material and methods A total of 119 patients with MCAO symptom were enrolled in this retrospective longitudinal cohort study. All patients met inclusion criteria of cerebral angiography by CT angiography or magnetic resonance angiography. Stroke severity was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Results We showed an average follow-up time of 46.8 months, within which 20 (19.6%) cases died and 14 (13.7%) cases had stroke recurrence. Using mRS as an evaluation index, the patients were divided into an unfavourable outcome group (mRS > 2, 48 cases) and a favourable outcome group (mRS ≤ 2, 54 cases). Logistic regression analysis suggests that age and NIHSS score were independent risk factors for a poor outcome value. Coexisting other cerebral vascular occlusion was an independent risk factor for stroke recurrence. Age was an independent risk factor for death. Conclusions The prognosis of patients with MCAO was generally optimistic, with higher survival rate and longer survival time. As compared, elder age and higher NIHSS score both tend to be associated with worse prognosis of survival. MCAO patients with other extracranial or intracranial vascular occlusion have higher risk of recurrent stroke. Death rate increases with age among the MCAO patients.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. This study summarizes the clinical, electrophysiological, genetic, and imaging features of six unrelated Chinese Han patients with HNPP. Age of onset was within the second decade in five patients, and 46 years of age in one patient. Weakness or numbness in a unilateral lower extremity was the most common symptom in 5 patients, and bilateral sensorineural hearing loss was also detected in one patient. Electrophysiological presentations suggested demyelinating sensory-motor polyneuropathy in the group. Magnetic resonance imaging (MRI) of the cervical and lumbar spine revealed varying degrees of degeneration in five patients, and mild kyphosis of cervical vertebral bodies in 2 teen-aged patients. In addition, cranial MRI of one patient showed scattered demyelination in the frontal lobes. Targeted next generation-sequencing (NGS) revealed a PMP22 deletion in five patients and a heterozygous c.199G>A mutation in exon 4 of PMP22 in one patient. The I92V variant of lipopolysaccharide-induced tumor necrosis factor (LITAF) gene was found in one patient. There was no relationship between the Ile92Val variant of LITAF and age of onset in this group, albeit the sample size was very small. (C) 2017 Elsevier Ltd. All rights reserved.

OBJECTIVE:To investigate the HIV drug resistance among HIV/AIDS patients who had received highly active antiretroviral treatment (HAATR) in Liangshan prefecture and related factors. METHODS:This investigation was conducted from August to October 2010. Data on epidemiology, treatment, CD4(+) T cell, viral load and drug resistance tests were collected. RESULTS:233 (73.50%) had a viral load of < 1000 copy/ml, with the median CD4(+) T cell count as 329 cell/µl. 26 samples appeared to be drug resistant, with the rate as 8.20%. Among 84 patients with antiviral therapy failure, the overall drug resistance rate was 30.95% (26/84). While 24 (28.57%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Among nucleoside reverse transcriptase inhibitors (NRTI), 7 (8.33%) were resistant. 1 (1.19%) had protease inhibitor (PI) resistance mutations identified. Factors that significantly associated with drug resistance would include: being injecting drug users (AOR = 3.37, 95%CI: 1.06 - 10.66, P = 0.0390), having had chronic diarrhea > 1 month (AOR = 8.38, 95%CI: 1.87 - 37.69, P = 0.0055), having had CD4(+) T cell < 200 (AOR = 3.48, 95%CI: 1.29 - 9.39, P = 0.0139), being residents from Butuo area (AOR = 17.68, 95%CI: 4.97 - 62.86, P < 0.0001). When comparing with other areas, data from Butuo showed that people who carried Yi ethnicity (AOR = 17.35, 95%CI: 2.01 - 149.73, P = 0.0095) and were literate (having had primary or higher levels of education) (AOR = 0.18, 95%CI: 0.08 - 0.42, P < 0.0001), being married or having cohabited relations (AOR = 8.17, 95%CI: 2.35 - 28.39, P = 0.001) were found to be less adherent (AOR = 0.05, 95%CI: 0.02 - 0.13, P < 0.0001) to the treatment. CONCLUSION:Successful antiviral outcomes were seen among those AIDS patients under treatment, in Liangshan prefecture. Resistance rates were significantly different in regions. For IDUs, enforcement on subjects including prevention on drug resistance, adherence to HAART and treatment for drug addiction should be strengthened and programs being integrated.

Objective To evaluate the reproducibility of an in-house HIV-1 drug resistance(HIVDR) genotyping test.Methods The reproducibility of an in-house HIVDR genotyping test was evaluated with 204 plasma samples,which had been tested from 2008 to 2010.The samples were randomly selected and retested with the same method.A fragment of HIV pol gene was extracted from plasma samples,amplified and sequenced.Drug resistance-related mutations were identified and interpreted through Stanford HIVdb program,and were compared with the results of previous testing.Results The rates of concordance in the overall resistance and resistance to specific antiretroviral drugs were 98.5%(201/204)and 92.2 %(188/204) between the results of the first and second testing,respectively.One hundred and sixty-seven(81.9%)specimens had same levels of resistance to specific antiretroviral drugs between the two sets of results.However,the discordant drug resistance-related mutations were found in 84 samples,among which 159 discordant codons were discovered.Most(149) of the codons were partially discordant.The inconsistent codons were most frequently found at position 71(13/204,6.4%) of the protease and 103(12/204,5.9%) of the reverse transcriptase(RT), respectively.Ten completely discordant codons were found at position 71 of the protease.Nucleoside reverse transcriptase inhibitor(NRTI) resistance-related sites were found at position 67,69,70,215 and 219 and non-nucleoside reverse transcriptase inhibitor(NNRTI) resistance-related sites were found at position 90,181 and 221 of RT regions,respectively.Conclusions The results revealed high concordance rates in both the incidence and the degree of drug resistance.The reproducibility of the in-house drug genotyping test procedure can be optimized by further standardization and personnel training.

The change of the expression of Cyclins in neurons of rats after focal cerebral ischemia was investigated. Ischemia was induced by temporary middle cerebral artery occlusion (MCAO). The experimental rats induced by MCAO were sacrificed on 7th and 14th day after reperfusion. The brain was taken out at 7th and 14th day after injury, and the expression of Cyclin D-1, E, A and B-1 in neurons of cerebral cortex or hippocampal CA1 region was detected by immunofluorescence and confocal microscope. The results showed that after MCAO, in the ipsilateral CA1 subfield of hippocampus the expression of Cyclin D-1, E, A and B-1 in neurons was significantly gradually up-regulated at 7th and 14th day after reperfusion (P<0.05) as compared with that in control group. In the ipsilateral cerebral cortex the expression of Cyclin D-1 and B-1 in neurons was notably gradually down-regulated at 7th and 14th day, and that of Cyclin E and A was significantly up-regulated at 14th day after reperfusion as compared with that in control group (all P<0.05). It was concluded that there was a differential sensitivity among neurons from different brain regions to ischemic injury. But all of them re-enter into cell cycle after MCAO.

[Objective ] To study the difference of CDK between astrocytes and neurons in adult rats. [Method] The expressions of CDK1 ,CDK2,CDK4 of astrocytes and neurons on cerebral cortex or hippocampal CA1 region of adult ruts were detected by immunofluorcscence and confocal microscope. [ Result ] All CDKs were expressed on nuclear or/and cytoplasm of postmitotic neurons,mainly on nuclear,of cerebral cortex or CA1 subfield of hippocampus; Whereas only a few astrocytes expressed CDKs in adult hippocampus and cerebral cortex and most of these astrocytes were located on hippocampal CA1 region. [ Conclusion ] Both astrocytes and neurons were expressed all CDKs in adult rats hippocampus and cerebral cortex. Compared with that of the astrocytes, the expressions of CDKs on mature neurons were remarkable.

Objective To study the difference of CDKIs between astrocytes and neurons in adult rats.Methods The expressions of p15Ink4b and p21ciplof astrocytes and neurons in adult rat cerebral cortex or hippocampus were detected by immunofluorescence and confocal microscope.Results p15Ink4b and p21cipl were expressed on nuclear or/and cytoplasm of postmitotic neurons, mainly on nuclear, of cerebral cortex or hippocampus; Whereas only a few astrocytes expressed CDKIs in adult rat hippocampus and cerebral cortex and most of these astrocytes were located on hippocampal region.Conclusions Both astrocytes and neurons in adult rat cerebral cortex and hippocampus express p15Ink4b and p21cipl which more CDKIs in neuron were expressed p15Ink4b and p21cipl in adult rats hippocampus and cerebral cortex. Compared with that of the astrocytes. the expressions of CDKIs on mature neurons were remarkable.

The spinal cord is well known to undergo inflammatory reactions in response to traumatic injury. Activation and proliferation of microglial cells, with associated proinflammatory cytokines expression, plays an important role in the secondary damage following spinal cord injury. it is likely that microglial cells are at the center of injury cascade and are targets for treatments of CNS traumatic diseases. Recently, we have demonstrated that the cell cycle inhibitor olomoucine attenuates astroglial proliferation and glial scar formation, decreases lesion cavity and mitigates functional deficits after spinal cord injury (SCI) in rats [Tian, D.S., Yu, Z.Y., Xie, M.J., Bu, B.T., Witte, O.W., Wang, W., 2006. Suppression of astroglial scar formation and enhanced axonal regeneration associated with functional recovery in a spinal cord injury rat model by the cell cycle inhibitor olomoucine. J. Neurosci. Res. 84, 1053-1063]. Whether neuroprotective effects of cell cycle inhibition are involved in attenuation of microglial induced inflammation awaits to be elucidated. In the present study, we sought to determine the influence of olomoucine on microglial proliferation with associated inflammatory response after spinal cord injury. Tissue edema formation, microglial response and neuronal cell death were quantified in rats subjected to spinal cord hemisection. Microglial proliferation and neuronal apoptosis were observed by immunofluorescence. Level of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) expression in the injured cord was determined by Western blot analysis. Our results showed that the cell cycle inhibitor olomoucine, administered at 1 11 post injury, significantly suppressed microglial proliferation and produced a remarkable reduction of tissue edema formation. In the olomoucine-treated group, a significant reduction of activated and/or proliferated microglial induced IL-1 beta expression was observed 24 h after SCL Moreover, olomoucine evidently attenuated the number of apoptotic neurons after SCI. Our findings suggest that modulation of microglial proliferation with associated proinflammatory cytokine expression may be a mechanism of cell cycle inhibition-mediated neuroprotections in the CNS trauma. (c) 2006 Elsevier B.V. All rights reserved.

Objective:The influence of olomoucine on microglial proliferation with associated inflammatory response after spinal cord injury has been determined.Methods:Microglial proliferation and neuronal apoptosis were observed by immunofluorescence.Level of the proinflammatory cytokine interleukin-1β（IL-1β）expression in the injured cord was determined by Western blot analysis.Results:the cell cycle inhibitor olomoucine,administered at 1 h post injury,significantly suppressed microglial proliferation and produced a remarkable reduction of tissue edema formation.In the olomoucine-treated group,a significant reduction of activated and/or proliferated microglial induced IL-1β expression was observed 24 h after SCI.Moreover,olomoucine evidently attenuated the number of apoptotic neurons after SCI.Conclusion:Our findings suggest that modulation of microglial proliferation with associated proinflammatory cytokine expression may be a mechanism of cell cycle inhibition-mediated neuroprotections in the CNS trauma.

Objective To observe the effects and toxicities of autologous peripheral blood stem cell transplantation (APBSCT) on progressive multiple sclerosis (PMS).Methods Sixteen patients suffering from PMS were treated with APBSCT. Autologous peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte-colony-stimulating factor(CY/G-SCF). CY/TBI (cyclophosphamide and total body irradiation) or BEAM (BCNU, etoposide, arabinosylcytosine, melphalan) was used as conditioning regimen. The probabilities of progression-free survival and the event-free survival were used to assess the effects and adverse experiences were recorded to detect the toxicities of APBSCT. Results The median follow-up time was 24 months. The probabilities of progression-free survival and the event-free survival wer 80%and 50%, respectively. The principal adverse events included nausea, vomiting, infections, trichomadesis, transient and mild abnormal liver enzymes and neurotoxicities. Two patients died due to severe infection and jaundice, respectively. Conclusions APBSCT appears feasible in PMS. However, more patients and longer follow-up would be required.