颅脑损伤后一氧化氮、一氧化氮合酶和内皮素变化

颅脑损伤后继发性脑损害已越来越受到重视,造成继发性损害的因素很多,其中内皮素(endothelin,ET)和一氧化氮(nitric oxide,NO)在继发性损害中所起的作用成为近年研究的热点,并存在很多争论.通过对63例颅脑损伤患者ET、NO和一氧化氮合酶(nitric oxide synthase,NOS)的测定,观察伤后ET、NO及NOS的变化情况,探讨该变化对外伤患者伤情判断的意义.     

Increased prevalence of Chlamydophila DNA in post-mortem brain frontal cortex from patients with schizophrenia

Infection can initiate symptoms of mental illness. It has been shown previously that Chlamydophila DNA is present six times more often in the blood of patients with schizophrenia than in the blood of control individuals. Monocytes, the main targets of Chlamydiaceae infection, are microglia precursors. We identified Chlamydiaceae infection using blinded brain DNA samples derived from the frontal cortex. Using PCR and sequence analysis, we found Chlamydophila DNA to be four times greater in patients with schizophrenia than in controls (schizophrenia: N=34, microbial DNA frequency 23.5%; controls: N=35, microbial DNA frequency 5.7%; P=0.045, OR=5.08). Persistent Chlamydophila-infected microglia or neuronal cells may impair neuronal circuits and thus be a mechanism for causing psychiatric illness in these patients.     

Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia.

Dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetyl-transferase (CAT) were measured in post-mortem brain samples from more than 50 patients dying with a hospital diagnosis of schizophrenia and an equal number of controls. GAD was measured in 14 different brain regions, and was significantly lower in both control and schizophrenia patients who died following a protracted illness. If GAD values from patients who died suddenly were compared, no significant differences were observed between the control and schizophrenia groups. There was also no differences between the CAT values measured in 13 different brain regions in the two groups. Noradrenaline values were not different in the two groups in most limbic areas or in the caudate nucleus, but were elevated in the schizophrenic group in nucleus accumbens and in anterior perforated substance. These differences were not, however, statistically significant. On the other hand dopamine concentrations in nucleus accumbens and in anterior perforated substance were significantly elevated (by 34 and 95 per cent, respectively) in the schizophrenia group as compared with controls, although dopamine values were not different in caudate nucleus, putamen, septal nuclei or amygdala. The finding of elevated concentrations of dopamine in certain areas of the limbic forebrain in schizophrenia is discussed in relation to current hypotheses of the involvement of dopamine in this illness, and the difficulties of determining whether the observed changes are related to chronic treatment with antischizophrenic drugs.     

Microarray analysis of postmortem temporal cortex from patients with schizophrenia

To examine molecular mechanisms associated with schizophrenia this study measured expression of approximately 12,000 genes in the middle temporal gyrus from 12 subjects with schizophrenia and 14 matched normal controls. Among the most consistent changes in genes with robust expression were significant decreases in the expression of myelination-related genes MAG, PLLP (TM4SF11), PLP1, ERBB3 in subjects with schizophrenia. There was also altered expression of genes regulating neurodevelopment (TRAF4, Neurod1, histone deacetylase 3), a circadian pacemaker (PER1), and several other genes involved in regulation of chromatin function and signaling mechanisms. These findings support the hypothesis that schizophrenia is associated with abnormalities in oligodendroglia and provide initial evidence suggesting a role for epigenetic mechanisms and altered circadian rhythms in this disorder.     

Increased neuronal nitric oxide synthase expression in brain following portacaval anastomosis

It has previously been suggested that increases of l-arginine uptake into brain following portacaval shunting may result in increased activities of constitutive neuronal nitric oxide synthase (nNOS). In order to further address this issue, nNOS protein and gene expression were studied by Western blot analysis using a monoclonal nNOS antibody and RT-PCR respectively in the brains of rats following portacaval shunting or sham operation. Portacaval shunting resulted in a 2-fold increase (P<0.01) in nNOS protein and a concomitant 2.4-fold increase (P<0.01) in nNOS mRNA. Increased nNOS activity in brain and the resulting increase in nitric oxide production could contribute to the increased cerebral blood flow and to the pathogenesis of hepatic encephalopathy in chronic liver disease.     

Staining intensity of brain iron in patients with schizophrenia: a postmortem study.

Evidence derived from both pharmacological and postmortem studies suggests that a disturbance of brain iron metabolism is involved in the pathophysiology of schizophrenia; i.e., the distribution of iron parallels that of dopamine, and variations in its brain concentration selectively modulate the binding affinity of the dopaminergic (D2) receptor. In the present study the authors examined the staining intensity of brain iron in postmortem specimens of 9 schizophrenic (SC) patients and 17 age-matched controls. Coronal sections were stained with the Perls's technique, photographed, and then studied using a computerized image analysis system. Optical density measurements were taken from the caudate nucleus, putamen, globus pallidus, and substantia nigra. This study revealed significant differences between groups only for the staining intensity of iron in the caudate nucleus (P less than 0.005). A review of the literature suggests that this finding may be the result of neuroleptic therapy and not a primary pathological feature of schizophrenia.     

Increased plasma nitric oxide level associated with suicide attempt in depressive patients

BACKGROUND: Nitric oxide (NO) is known to influence cerebral monoaminergic activity, including the activity of serotonin. We evaluated plasma NO metabolite (NO(x)) levels in depressive patients with and without a recent history of suicide attempt. METHOD: Plasma NO(x) levels were measured in 39 depressive patients who had recently attempted suicide, 44 non-suicidal depressed patients, and 70 normal controls. The severity of depression was measured with the Hamilton's Depression Rating Scale. The lethality of the suicide attempt was scored using Weisman and Worden's risk-rescue rating scale and Lethality Suicide Attempt Rating Scale. RESULTS: Plasma NO(x) levels were significantly higher in suicidal depressive patients than non-suicidal depressive patients or normal control subjects (Z=-2.472, p=0.013). However, higher plasma NO(x) levels in suicidal depressive patients were significantly related to a lower lethality of suicide attempts and lower severity of depression. CONCLUSIONS: Our study suggests that increased plasma NO(x) level is associated with suicide attempts in depressive patients. Moreover, higher plasma NO(x) level is related with suicide attempts in mild depressed patients. However, further studies are required to understand the role of NO system in depression and suicidal behavior.     

Protein expression profiling of postmortem brain in schizophrenia

Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) enables the sensitive, high-throughput protein profiling of complex biological mixtures. In combination with bioinformatics, this technology has the potential to identify combinations of spectral peaks that can differentiate individuals with a particular disease from normal controls. SELDI-TOF-MS was used to screen postmortem tissue derived from the dorsolateral prefrontal cortex of individuals with schizophrenia (n = 34) and matched controls (n = 35), obtained from the Stanley Foundation Neuropathology Consortium. Tissue samples were homogenized in urea buffer, applied to four different chip arrays which possess different chromatographic surfaces, and analyzed using the Ciphergen ProteinChip Biomarkers System (Model PBS II). Protein expression profiles of the schizophrenia and control groups were compared and analyzed using the Ciphergen Express (CE) and Biomarker Patterns Software (BPS) package. We detected several protein peaks whose intensities differed between the schizophrenia and control groups to a highly significant degree. A combination of these peaks was capable of distinguishing between schizophrenia and controls with a sensitivity and specificity of about 70%. The classification model that distinguished schizophrenia from controls was complex, suggesting that the biochemical abnormalities underlying schizophrenia are heterogeneous. Our results suggest that SELDI-TOF-MS has the potential for distinguishing individuals with schizophrenia from normal controls and may eventually lead to a better understanding of the classification, diagnosis and pathogenesis of this disorder.     

Increased in-hospital mortality from COVID-19 in patients with schizophrenia

BackgroundThere is limited information describing the presenting characteristics and outcomes of patients with schizophrenia (SCZ) requiring hospitalization for coronavirus disease 2019 (COVID-19).AimsWe aimed to compare the clinical characteristics and outcomes of COVID-19 SCZ patients with those of non-SCZ patients.MethodThis was a case-control study of COVID-19 patients admitted to 4 AP–HM/AMU acute care hospitals in Marseille, southern France. COVID-19 infection was confirmed by a positive result on polymerase chain reaction testing of a nasopharyngeal sample and/or on chest computed scan among patients requiring hospital admission. The primary outcome was in-hospital mortality. The secondary outcome was intensive care unit (ICU) admission.ResultsA total of 1092 patients were included. The overall in-hospital mortality rate was 9.0%. The SCZ patients had an increased mortality compared to the non-SCZ patients (26.7% vs. 8.7%, P = 0.039), which was confirmed by the multivariable analysis after adjustment for age, sex, smoking status, obesity and comorbidity (adjusted odds ratio 4.36 [95% CI: 1.09–17.44]; P = 0.038). In contrast, the SCZ patients were not more frequently admitted to the ICU than the non-SCZ patients. Importantly, the SCZ patients were mostly institutionalized (63.6%, 100% of those who died), and they were more likely to have cancers and respiratory comorbidities.ConclusionsThis study suggests that SCZ is not overrepresented among COVID-19 hospitalized patients, but SCZ is associated with excess COVID-19 mortality, confirming the existence of health disparities described in other somatic diseases.     

Increased brain membrane fluidity in schizophrenia

Recent findings showing significant correlations between phospholipase A2 (PLA2) activity and structural changes in schizophrenic brains contribute to the membrane hypothesis of schizophrenia, which was hampered because a clean functional link between elevated PLA2 activity and brain structure was missing (Neuroimage, 2010; 52: 1314-1327). We measured membrane fluidity parameters and found that brain membranes isolated from the prefrontal cortex of schizophrenic patients showed significantly increased flexibility of fatty acid chains. Our findings support a possible link between elevated PLA2 activity in cortical areas of schizophrenic patients and subsequent alterations of the biophysical parameters of neuronal membranes leading to structural changes in these areas.     

Increased nitric oxide products in CSF in primary progressive MS may reflect brain atrophy

Because nitric oxide (NO) is a putative mediator of oligodendrocyte damage in the primary progressive form of MS (PPMS), the authors analyzed the levels of NO oxidation products in CSF and plasma from 25 patients with PPMS and 15 controls. The levels of nitrite + nitrate (NOx) in CSF were fourfold higher in patients with PPMS than in controls (p < 0.001), whereas the concentrations in plasma were similar. These data suggests involvement of NO in nervous tissue damage in PPMS.     

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO _x ) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO _x /Cr ratio and number of NO _x peaks was significantly greater in the migraine group compared with controls ( P  = 0.01 and P  = 0.007, respectively). In the second approach, high NO _x values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO _x persisted being pulsatile, and migraineurs had more peaks compared with controls ( P  = 0.01). In seven patients, NO _x peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16–7.77; no overlap of 95% CI). In four patients, NO _x peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO _x excretion between control and migraine populations, the variable temporal association of NO _x peaks and headaches suggests a complex role of NO in this condition.     

Increased nitric oxide synthase in the vasculature of the epaulette shark brain following hypoxia.

Epaulette sharks inhabiting reef platforms are exposed to hypoxic and hyperoxic cycles. The adaptive mechanisms used to prevent neurological damage during these cycles have not been examined. Nitric oxide has a neuroprotective role in some hypoxia-tolerant species. We examined epaulette brains following a severe experimental hypoxic regimen (0.39 mgO2/l for 2 h) and compared nitric oxide synthase (NOS) expression with that in normoxic controls using NADPH-diaphorase staining. Intense NOS activity occurred in microvasculature following exposure to a severely hypoxic environment in contrast to the low levels seen in controls. We established for the first time that the epaulette shark was hypoxia-tolerant because there was no delayed phase of neuronal apoptosis. Enhanced NOS production in response to hypoxia may cause vasodilation, which would maintain the appropriate metabolic environment for continued neuronal survival during exposure to hypoxia.     

Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease.

Nitric oxide (NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of.NO in the development of progressive disease we measured the NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit : creat. urine) and neopterin (neopt : creat.urine) to creatinine ratios compared to NC subjects. (Median[25th - 75th%] nit : creat.urine: NC=1183[962 - 1365] vs DD=1245[875 - 2403], AIDS=1686[1231 - 2531], and RA=1950[1214 - 2726] mumol/mol, P<0.001 and median[25th - 75th%] neopt : creat.urine: NC=99[76 - 151] vs DD=163[119 - 266], AIDS=972[653 - 1456], and RA=389[257 - 623] mu mol/mol, P<0.001). Patients with early DD and RR MS had significantly elevated nit : creat.urine compared to patients with progressive MS (nit : creat. urine: 1612[1020 - 2733] vs 1159[790 - 1641] mu mol/mol, P=0.006). The nit : creat.urine and neopt : creat.urine did not correlate with clinical relapse or MRI activity. Excretion of.NO metabolites is increased in patients with early or relapsing-remitting disease.NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.     

慢性精神分裂症男性患者血浆一氧化氮及其合成酶活性的临床研究

目的 探讨慢性精神分裂症男性患者血浆一氧化氮(NO)浓度及其合成酶活性与患者认知功能和临床症状之间关系.方法 于2020年1—10月在连云港地区精神专科医院(连云港市第四人民医院、赣榆区康复医院、东海县精神病医院、灌云县精神病医院)选取96例慢性精神分裂症男性患者作为患者组,同期在连云港市招募年龄18～60岁的88例健...     

Increased neurons containing neuronal nitric oxide synthase in the brain of a hypoxic-ischemic neonatal rat model

We evaluated the temporal profile of the number of neurons containing neuronal nitric oxide synthase (nNOS neurons) in the brain of a neonatal hypoxic-ischemic rat model. Hypoxic-ischemic insults were produced in the brains of 7-day-old rat pups using a combination of unilateral carotid artery ligation and hypoxic (8% oxygen) exposure. Sections of brain from rats killed at 0–24 h after the onset of hypoxia were stained immunohistochemically using a polyclonal anti-nNOS antibody. Histological changes of neuronal injury were evaluated in the adjacent Nissl stained sections. The number of nNOS neurons in the hemisphere ipsilateral to the carotid ligation was significantly increased (P < 0.05) at 3 h, when the neuronal injury consisted of clusters of degenerating hyperchromic neurons. Neuronal degeneration and an increased number of nNOS neurons were seen only in the ipsilateral hemisphere and the increase was most prominent in the dorsolateral area of the striatum. The increase in the number of nNOS neurons continued at 6 h, when the area of neuronal injury continued to expand. At 24 h, the neuronal injury was diffuse, and the number of nNOS neurons on the ipsilateral side significantly decreased. The increase of the number of nNOS neurons in the early phase of neonatal neuronal injury suggests its possible involvement in the hypoxicischemic injury. The delineation of its role in neuronal injury may lead to an improvement in managing neonatal hypoxic-ischemic brain injury.