Investigations of neurotoxicity and neuroprotection within the nucleus basalis of the rat

The present study investigated the specific ways by which cytotoxicity due to glutamate receptor stimulation could be attenuated by the administration of agonists and antagonists of the ionotropic and metabotropic glutamate receptors within the nucleus basalis magnocellularis (NBM) of rats as measured by cortical choline acetyltransferase activity. The results of these studies suggest that (1) the cytotoxicity of ibotenate to NBM cholinergic cells is not dependent upon stimulation of metabotropic glutamate receptors, but results from activation of (NMDA) receptors, (2) the cytotoxicity of quisqualate to cholinergic cells within the NBM is not dependent upon stimulation of NMDA or metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by administration (i.p.) of the un-competitive NMDA antagonist memantine (30 mg/kg), resulting in plasma levels of 2.5 μg/ml, a concentration known to block efficiently NMDA receptors in vitro. Finally, performance of a food-motivated, delayed-alternation task on a T-maze was impaired by injections of NMDA into the NBM, but was prevented by co-administration of NMDA with memantine.     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Analysis of kidney volume growth during the fetal period in humans

Summary The growth of fetal kidney volume was studied in 290 specimens taken from 145 fresh human fetuses (85 males and 60 females) with gestational age ranging from 13 to 36 weeks postconception (WPC). Normative equations and curves of the growth of renal volume were obtained for male and female fetuses and for the whole sample in the second trimester (13–24 WPC) and in the third trimester (25–36 WPC) of gestation. There was no difference between the growth in volume of the right and left kidneys. Fetal kidney volume increases with a more intense rhythm in the early fetal period (13–24 WPC). During the second trimester, there was no difference between the values for renal volume of male and female fetuses. In the third trimester, male fetuses had renal volumes significantly greater than the female fetuses. The normative parameters of renal volume could have practical applications in detection and monitoring of renal anomalies in fetal and perinatal urology.Supported by grants 302, 369/86.4/BM-FV from the National Conucil of Scientific and Technological Development (CNPq, Brazil) and Grant E.29/170.787/89 from the Rio de Janeiro Foundation for Research Support (FAPERJ).     

Inhibition or enhancement of kindling evolution by antiepileptics

Summary The influence of antiepileptics on the evolution of rat amygdaloid kindling was studied.Under placebo conditions clonic convulsions and a spike-wave EEG pattern developed. Diazepam, clonazepam, clobazam and phenobarbital were most effective in suppressing the evolution of kindling; the effects of valproate sodium, ethosuximide and acetazolamide were somewhat less pronounced in this respect. Carbamazepine, oxcarbazepine and phenytoin, on the other hand, enhanced kindling development, i.e. the increase in duration of after-discharge was faster than in the placebo group. The results indicate that under the above experimental conditions drugs with no anti-absence component can be distinguished from those with an anti-absence component. The mechanism of action underlying the observed effects is not yet known; the hypothesis that under special conditions protective inhibitory neuronal activity can develop to absence type seizures is proposed.     

Noxious stimuli excite neurons in nucleus submedius of the normal and arthritic rat

Anatomical studies have revealed the existence of an ascending pathway originating in the spinal cord and medullary dorsal horn, relaying in nucleus submedius (Sm) in medial thalamus and terminating in ventrolateral orbital cortex. It has been suggested that this pathway may be involved in the transmission of nociceptive information. In the present study extracellular recordings were obtained from neurons in Sm of anesthetized arthritic and normal rats. Mechanical and thermal stimuli were delivered to various regions of the body to determine the types of somatic stimuli which could activate Sm neurons. Over 40% of the 146 neurons studied responded to somatic stimuli. In the normal rats only high intensity mechanical and thermal stimuli were effective in inducing responses. In the arthritic rats lower intensity mechanical stimuli, joint movements and high intensity thermal stimuli were effective. Such stimuli produce nociceptive reactions in the freely moving arthritic rat. Almost all the responses were excitatory and generally lasted the entire duration of the 15-s stimuli employed. In some cases after-discharges were present. The receptive fields of the neurons were in almost all cases large and bilateral. These findings support the hypothesis that Sm may be involved in mediating the affective-motivational aspects of pain.     

血管重塑对大鼠血管成形术后再狭窄的影响

目的：建立大鼠颈动脉再狭窄模型，原位灌注固定取材。评价PTA后血管重塑（VR）的动态变化规律，定量分析血管重塑在血管再狭窄过程中的变化及作用。方法：制作70只SD雄性大鼠颈总动脉再狭窄模型，分原位灌注实验组、对照组，于术后1h、3、7、14、28和42天原位灌注固定取材，行HE染色、Masson染色，观察标本血管狭窄情况。结果：①血管重塑指数（VRI）在PTA后即刻最大，3天组明显降低，7天组稍有增大，其后不断减小，剩余血管腔面积百分比同VRI的变化曲线基本一致。②FFA后，血管腔面积总体呈逐渐缩小趋势，内弹力板围绕面积（IELA）1h组较对照组明显增大，3天组较1h组明显缩小，14、28、42天组较对照组明显缩小。外弹力板围绕面积（EELA）逐渐缩小。EELA、IELA的变化与血管腔面积变化呈正相关。③VRI与血管腔面积的变化呈正相关，新生内膜面积与剩余狭窄率、血管腔面积无直线相关。结论：再狭窄过程中存在扩张性重塑和收缩性重塑现象，管腔的狭窄与否取决于血管重塑指数的变化，而不是新生内膜的变化，新生内膜的形成是血管重塑过程中的一部分。IELA和EELA可作为判断管腔狭窄及评价血管重塑的指标。     

Inhibition of glutamate release in rat hippocampus by kynurenic acid does not protect CA1 cells from forebrain ischemia

We assessed the effect of a broad spectrum glutamatergic receptor antagonist, kynurenic acid (500 mg/kg) on ischemia-induced hippocampal glutamate release and neuronal damage. Kynurenic acid significantly decreased glutamate release during ischemia but had no effect on the hippocampal lesion. Some protection was observed in the cortex and in the striatum. These data suggested that the extracellular accumulation of glutamate during forebrain ischemia does not play a major role in the hippocampus.     

ApoMT对CdMT肾毒性保护作用研究

本文研究了去除金属离子的金属硫蛋白（ApoMT）对镉金属硫蛋白（CdMT）肾毒性作用的影响。结果发现，与单独给予CdMT比较，ApoMT能降低尿蛋白量和尿碱性磷酸酶（AKP）活性，并能促进尿Cd的排泄。肾组织形态学结果显示肾近曲小管损伤程度明显减轻。提示ApoMT对CdMT肾小管损伤具有保护作用。