Reduction of nerve growth factor receptor immunoreactivity in ischaemic gerbil hippocampal CA1 neurons after treatment with L-threo-3,4-dihydroxyphenylserine (DOPS)

Abstract

Nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells can be increased after the treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). Since the increase of NGF is not blocked by the treatment with decarboxylase inhibitor, DOPS may have direct effect to increase the NGF content. NGF and its receptor (NGFR) are suggested to play an important role in the neuronal survival and regeneration under pathologic conditions. In this study, we studied a possible protective effect of DOPS against the hippocampal CA1 cell death after transient forebrain ischaemia in gerbils in relation to the change of NGFR immunoreactivity. We found that treatment with DOPS (300 mg kg^–1) in combination with a decarboxylase inhibitor (benserazide, 10 mg kg^–1) protected ischaemic hippocampal CA1 cell against delayed neuronal death (neuronal density = 125 ± 24 mm^–1) as compared to the treatment with vehicle (49 ± 11 mm^–1) (p < 0.01). The immunoreactivity for NGFR was scarcely present in the sham-control CA1 area but was induced from 1 h and markedly expressed at 7 days after recirculation in the vehicle group. However; it was slightly and transiently induced from 8 h to 2 days in the DOPS plus benserazide treated group. These data suggest that the protective role of DOPS on the ischaemic hippocampal CA1 cells may act through the NGF and its receptor system. [Neurol Res 1994; 16: 201–204]     

Anoxic depolarization determines ischemic brain injury

Abstract

To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we examined the correlation between AD and ischemia-induced neuronal injury. Twenty-eight rats underwent transient forebrain ischemia with lowering of blood pressure and bilateral carotid occlusion while direct current shiftslelectrocorticogram, and cortical blood flow (COBF) were epidurally recorded from the right parietal cortex. One week later the right parietal cortex was studied histopathologically. AD appeared 0.5-3.0 min after carotid occlusion in 21 of28 animals. Circulation was reinitiated 75 min afterAD onset in 77 rats (group A) and 10 min after onset in 70 rats (group B). AD did not develop during 20 min of ischemia in 7 rats (group C). All 72 rats (6 from group A and 6 from group B) in which CoBF decreased below 9.5% of control flow exhibited AD. Histopathologic examination disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 74 rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of5 rats from group A. Ischemic neuronal changes were absent or minimal in only 7/5 ofgroup A animals, a much lower fraction than in group B (4/4, p<0.05) or in group.C (5/5/, p<0.05). When CoBF remained above 20% of control flow during ischemia (2 rats) no AD or irreversible injury occurred. The present study suggests that AD is a more reliable determinant of irreversible brain injury than degree of CBF reduction, and also demonstrates that 75 min is the critical duration of AD for irreversible brain injury at brain temperatures around 37° C. [Neural Res 1998; 20: 343-348]     

Knowledge of TIA among general practitioners and emergency department physicians. A questionnaire survey in a French semi-rural area

Background and objective

Management of transient ischemic attacks (TIAs) is of vital importance in an attempt to prevent stroke. However, suboptimal management still raise concern among general practitioners (GPs) and emergency department (ED) physicians—the first medical contact of most TIA patients. This may relate to their poorly updated knowledge about TIA. The study was designed to assess knowledge of TIA among these non-neurologists.

Methods

The study was a post-mailed questionnaire survey among GPs and ED physicians. The questionnaire related to selective clinical aspects on TIA.

Results

There were a total of 85 respondents for analysis, mostly GPs (n = 64; 75.3%), out of 177 mailed physicians. Response rate was 52.7%. Many of these respondents were unaware of the newly proposed TIA definition (59%), unfamiliar with TIA mimics and predictors of post-TIA early stroke recurrence and therefore with the rationales underlying the need of emergency management of TIA. More than one third (39%) were unaware of the relevant national guidelines. Guidelines-aware respondents performed better in most part of the mailed questionnaire.

Conclusion

Our results show that poorly updated knowledge about TIA among non-neurologists represents a potential contributing factor to the persisting sub-optimal management of the disorder. Although further studies are needed to confirm this, improved continuous medical education of this group of health care professionals appears warranted.     

Risk of Wheezing Attacks in Infants With Transient Tachypnea Newborns

Background:

The most common reason of respiratory distress in the newborn is transient tachypnea of the newborn (TTN). There are some reports saying that TTN is associated with increased frequencies of wheezing attacks.

Objectives:

The aims of this study were to determine the risk factors associated with TTN and to determine the association between TTN and the development of wheezing syndromes in early life.

Materials and Methods:

In a historical cohort study, we recorded the characteristics of 70 infants born at the Shohadaye Kargar Hospital in Yazd between March 2005 and March 2009 and who were hospitalized because of TTN in the neonatal intensive-care unit. We called their parents at least four years after the infants were discharged from the hospital and asked about any wheezing attacks. Seventy other infants with no health problems during the newborn period were included in the study as the control group.

Results:

The rate of wheezing attacks in newborns with TTN was more than patients with no TTN diagnosis (P = 0.014). TTN was found to be an independent risk factor for later wheezing attacks (relative risk [RR] = 2.8).

Conclusions:

The most obvious finding of this study was that TTN was an independent risk factor for wheezing attacks. So long-term medical care is suggested for these patients who may be at risk, because TTN may not be as transient as has been previously thought.     

TRPV4通道蛋白在肿瘤发生发展中的研究进展

TRPV4通道是瞬时受体电位通道家族(TRP)的成员,属非选择性阳离子通道,可被热、机械力、佛波醇酯衍生物等多种理化刺激所激活,参与维持细胞的正常功能。近年来,TRPV4在细胞增殖、分化、凋亡及迁移中的作用研究颇多,其异常表达与肿瘤的发生发展密切相关。笔者就该通道在肿瘤中的研究进展进行综述。     

Immunohistochemical localization of TRPC6 in the rat substantia nigra

Transient receptor potential channels (TRPC) are plasma membrane, nonselective cationic channels and have been proposed as candidates involved in the regulation of cellular Ca2+ influx [D.E. Clapham, L.W. Runnels, C., Strubing, The TRP ion channel family, Nat. Rev. Neurosci. 2 (2001) 387-396; A. Martorana, C. Giampa, Z. DeMarch, M.T. Viscomi, S. Patassini, G. Sancesario, G. Bernardi, F.R. Fusco, Distribution of TRPC1 receptors in dendrites of rat substantia nigra: a confocal and electron microscopy study, Eur. J. Neurosci. 24 (2006) 732-738]. Studies on regional localization patterns of TRPCs are necessary to provide helpful guidelines for correlating current types with particular channels. In this study, we examined the distribution of one particular member of TRPC superfamily, namely, TRPC6, in the substantia nigra of normal rat brain. Single and double label immunohistochemistry were employed to perform both light and confocal microscopy observations. Our single label studies showed that, in the substantia nigra, TRPC6 labeled the perikarya with a diffuse and intense immunoreaction product distributed throughout cell cytoplasm whereas only a light immunostaining was observed in the cell nuclei. No labeling of axon or terminals was observed, although TRPC6 was evenly distributed in the neuropil. Our dual label studies showed a TRPC6 immunoreactivity pattern that was localized into the proximal dendrites and axon hillock of the large dopaminergic neurons identified by TH immunoreaction. Furthermore, our double label immunofluorescence study for TRPC6 and mGluR1 showed a complete co-localization of the two markers in the substantia nigra. Moreover, TRPC6 did not co-localize with synaptophysin. Thus, our study shows the postsynaptic localization of TRPC6 and its association with mGluR1 in the midbrain dopamine neurons.     

The effects of isoproterenol on abnormal electrical and contractile activity and diastolic calcium are attenuated in myocytes from aged Fischer 344 rats

We investigated whether the age-related decrease in sensitivity of the heart to catecholamines was accompanied by changes in Ca(2+) homeostasis and abnormal electrical and contractile activity caused by beta-adrenergic receptor (beta-AR) stimulation. Ventricular myocytes were isolated from young adult (3 months) and aged (24 months) male Fischer 344 rats. Unloaded cell shortening was measured in field-stimulated myocytes (2Hz, 37 degrees C); membrane currents and action potentials were measured with microelectrodes. Contractile responses to the non-selective beta-AR agonist, isoproterenol were significantly decreased in aged myocytes compared to younger myocytes and aged myocytes were less sensitive to isoproterenol. In contrast, Ca(2+) transients measured simultaneously with contractions were similar between groups. Isoproterenol increased sarcoplasmic reticulum Ca(2+) stores in both groups, but the increase was larger in aged cells. However, signs of Ca(2+) overload induced by isoproterenol were reduced with age. Diastolic Ca(2+) accumulation, contracture and the incidences of transient inward current, oscillatory afterpotentials (OAPs), aftertransients and aftercontractions induced by isoproterenol also were reduced with age. These results demonstrate that aged myocytes exhibit fewer signs of Ca(2+) overload in response to isoproterenol than young adult myocytes. These age-related changes in intracellular Ca(2+) may protect the aging heart against induction of arrhythmias initiated by OAPs.(1).     

Can lower risk patients presenting with transient ischaemic attack be safely managed as outpatients?

This study aimed to examine outcome in low risk transient ischaemic attack (TIA) patients presenting to emergency departments (ED) in a regional Australian setting discharged on antiplatelet therapy with expedited neurology review. All patients presenting to Gosford or Wyong Hospital ED with TIA, for whom faxed referrals to the neurology department were received between October 2008 and July 2010, were included in this prospective cohort study. Classification of low risk was based on an age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD²) score <4 and the absence of high risk features, including known carotid disease, crescendo TIA, or atrial fibrillation. Patients with ABCD² scores ⩾4 or with high risk features were discussed with the neurologist on call (a decision regarding discharge or admission was then made at the neurologist’s discretion). Patients were investigated with a brain CT scan and/or CT angiography, routine pathology, and an electrocardiogram. All discharged patients were commenced on antiplatelet therapy and asked to follow up with their local medical officer within 7 days. The patients were contacted by the neurology department to arrange follow-up. Our primary outcome was the number of subsequent strokes occurring within 90 days. Of 200 discharged patients for whom referrals were received, three patients had a stroke within 90 days. None of these would have been prevented through hospitalisation. In conclusion, medical assessment, expedited investigation with immediate commencement of secondary prevention and outpatient neurology review may be a reasonable alternative to admission for low risk patients presenting to the ED with TIA.     

Factors associated with early recurrence at the first evaluation of patients with transient ischemic attack

We aimed to identify factors easily collected at admission in patients with transient ischemic attack (TIA) that were associated with early recurrence, so as to guide clinicians’ decision-making about hospitalization in routine practice. From September 2011 to January 2013, all TIA patients who were referred to the University Hospital of Dijon, France, were identified. Vascular risk factors and clinical information were collected. The etiology of the TIA was defined according to the results of complementary examinations performed at admission as follows: large artery atherosclerosis (LAA-TIA) TIA, TIA due to atrial fibrillation (AF-TIA), other causes, and undetermined TIA. Logistic regression analyses were performed to identify factors associated with any recurrence at 48 hours (stroke or TIA). Among the 312 TIA patients, the etiology was LAA-TIA in 33 patients (10.6%), AF-TIA in 57 (18.3%), other causes in 23 (7.3%), and undetermined in 199 (63.8%). Early recurrence rates were 12.1% in patients with LAA-TIA, 5.3% in patients with AF-TIA, 4.3% in patients with another cause of TIA, and 1.0% in patients with undetermined TIA. In multivariable analysis, the LAA etiology was independently associated with early recurrence (odds ratio [OR]: 12.03; 95% confidence interval [CI]: 1.84–78.48, p = 0.009). A non-significant trend was also observed for AF-TIA (OR: 3.82; 95% CI: 0.40–36.62, p = 0.25) and other causes (OR: 3.73; 95% CI: 0.30–46.26, p = 0.31). A simple initial assessment of TIA patients in the emergency room would be helpful in targeting those with a high risk of early recurrence and who therefore need to be hospitalized.     

前循环TIA患者血清总胆红素水平与ABCD2评分

目的探讨动脉粥样硬化(AS)性前循环短暂性脑缺血发作(TIA)患者血清总胆红素(T.Bil)水平与其ABCD2评分的相关性。方法收集前循环TIA患者133例进行ABCD2评分,根据评分分为低危亚组、中危亚组和高危亚组,收集其血清T.Bil水平资料,比较三组间血清T.Bil平均水平,分析血清T.Bil水平与ABCD2评分的相关程度及其临床意义。结果 TIA患者血清T.Bil水平较对照组显著降低,差异有统计学意义(P<0.05)。Kruskal-Wallis H检验显示,三组间血清T.Bil平均水平差异有统计学意义(P=0.004),高危亚组[(7.59±2.05)μmol/L]低于中危亚组[(9.45±3.08)μmol/L],中危亚组低于低危亚组[(11.53±2.26)μmol/L](均P<0.05)。经Spearman秩相关系数检验,血清T.Bil水平与ABCD2评分呈负相关(r=-0.269,P=0.002)。结论 TIA患者血清T.Bil水平随ABCD2评分的增高而降低,并与ABCD2评分呈负相关。