Substantia nigra damage induced by ischemia in hyperglycemic rats

Summary Preischemic hyperglycemia induced by feeding or glucose infusion worsens the brain damage and the clinical outcome following ischemia of a given duration and density, and characteristically causes postischemic seizure activity. Light microscopy has previously showed that, in the rat, transient hyperglycemic ischemia induced by bilateral carotid occlusion in combination with arterial hypotension causes a uni- or bilateral lesion in the pars reticulata of the substantia nigra. Since this region has a central role in preventing seizure discharges the present study was carried out to determine the ultrastructural characteristics of this lesion. In rats with 10 min of transient hyperglycemic ischemia followed by recirculation for 1 to 18 h, the pars reticulata of the substantia nigra showed signs of status spongiosus, as well as extensive nerve cell alterations. These changes were observed after all recovery periods studied. The spongiotic appearance was mainly caused by swelling of dendrites and, to a lesser degree, by astrocytic swelling. The dendrites were expanded at all recovery times but the severity increased during the later periods of recirculation. These swollen dendrites contained severely expanded mitochondrias and endoplasmic reticulum. The cytoskeletal elements showed disordered lining of microtubules. Two major types of nerve cell alterations were present: a pale and a dark variety. The pale type was the most frequent cell alteration. It occurred in all experimental groups and at all time points. Redistribution of the nuclear chromatin and of cytoplasmic organelles as well as swelling of the same type as in the dendrites were the essential changes. The dark neurons were much fewer in number and occupied a peripheral position in the pars reticulata. Astrocytic foot processes appeared to be dilated around the dark neurons. Swelling of astrocyte processes was most pronounced in the 1 h recovery animals. Both types of neurons showed severe mitochondrial alterations of the type observed in dendrites. Occasionally, mitochondrial alterations were found in astrocytic processes as well. Blood vessel alterations were lacking. Previous studies have shown that in this model of ischemia the substantia nigra has a relatively well-preserved blood perfusion. In view of this the extensive histopathological lesions are surprising. We speculate that the lesions primarily involve excitotoxic damage to dendrites, with pronounced lactic acidosis playing a contributory role in causing axonal and glial pathology as well.Supported by grants from the Swedish Medical Research Council (project 12X-03020 and project 14X-263) and from the U.S. Public Health Service via the N.I.H. (grant No. 5 RO1 NS07838)     

Hematogenous metastases of the human brain – Characteristics of peritumoral brain changes: A review

The brain is an important site of hematogenous metastases from malignanttumors in other organs. The effects on the brain is a combination of tissuedestruction induced by invading tumor cells and reactive alterationsoccurring around the metastases. This review focuses on neuropathologicalchanges around hematogenous metastases of the human brain. The peritumoralbrain parenchyma shows structural and functional changes of theintracerebral microvessels and edema. The endothelial cells of peritumoralmicrovessels express glucose transporter protein (GLUT 1) in the same way asthe normal brain. Reduction in immunostaining to GLUT 1 may occur in themicrovessels located within the metastases. This would indicateabnormalities of the blood-brain barrier in tumor vessels but normal barrierfunction in the peritumoral region. Reactive astrocytes and activatedmicroglial cells are both involved in the process of peritumoral gliosis.Activated glial cells produce numerous biological active compounds includingendothelin-1 which after release from such cells can influence the structureand function of the peritumoral brain tissue. Lesions of oligodendrocytesand edema may be implicated in myelin degeneration. Finally, metastases willinduce axonal and neuronal injuries as indicated by a recent study onexpression of -amyloid precursor protein (APP) in reactive axonalswellings.     

Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons

We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).     

The Ileal Ureter Neobladder is Associated with a High Success and a Low Complication Rate

Purpose

Several different methods to construct a bladder substitute after cystectomy have been described. We evaluated our experience with the Studer ileal ureter neobladder during the last 5 years.

Materials and Methods

We reviewed retrospectively the results in 32 patients who underwent construction of a slightly modified ileal neobladder from that originally described. Mean followup was 25 months (range 6 to 68).

Results

Patients experienced few complications and only 1 required reoperation. Daytime and nighttime continence rates were 94 and 74 percent, respectively. One patient sustained a ureteral stricture resulting in hydronephrosis (1 of 64 renal units).

Conclusions

The results reveal the ileal neobladder to be an easily constructed pouch with a low complication rate, and a high success rate in regard to continence and the establishment of adequate capacity at low pressure. Within the study period upper tract preservation was excellent. However, a 10 to 15-year followup is indicated to confirm our initial results.     

Absorbable stapling techniques in continent urinary diversion

Summary The principle of bowel detubularization to decrease peristaltic pressure and increase reservoir capacity is applied in contemporary continent urinary diversions. The process of detubularization and refashioning of the spatulated bowel segment approximates 1 of operating time and is the most time-consuming aspect of pouch construction. The employment of devices applying absorbable staples (absorbable staplers) has substantially reduced the time required to fashion bowel reservoirs. This article reviews the adaptation of the absorbable stapler to continent urinary diversion using small- and large-bowel segments.     

Metoprolol does not reduce platelet aggregability during sympatho-adrenal stimulation

Summary The possibility that -adrenoceptor blockers, especially ₁-selective agents might inhibit platelet function is of considerable interest, as this might be of pathophysiological importance in cardiovascular diseases. Platelet function, however, is difficult to assess and in vivo related data are scarce.The effect of one week of treatment with metoprolol 200 mg/day on platelet aggregability during mental stress (colour word conflict test; CWT) and low and high dose adrenaline infusions has been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy male volunteers. Platelet function in vivo was assessed using ex vivo filtragometry, and the urinary excretions of -thromboglobulin (HMW -TG) and 11-dehydro-TxB₂ (a thromboxane metabolite). Conventional in vitro aggregometry and the urinary levels of 2,3-dinor-6-keto-PGF₁ (a prostacyclin metabolite) were also studied.During the interventions there was increased platelet aggregability in vivo, as filtragometry readings were shortened by 41±11% during high dose adrenaline infusion, urinary HMW -TG levels increased and urinary 11-dehydro-TxB₂ tended to increase. In contrast, platelet sensitivity to ADP in vitro was reduced. The urinary 2,3-dinor-6-keto-PGF₁ levels were increased during the interventions.Despite the cardiovascular and biochemical signs of -adrenoceptor blockade at rest and during the interventions, metoprolol failed to influence platelet function in vivo, as measured by ex vivo filtragometry, or urinary HMW -TG or 11-dehydro-TxB₂ levels. It tended rather to enhance the stress response measured by ex vivo filtragometry. Platelet aggregability in vitro and urinary 2,3-dinor-6-keto-PGF₁ levels were not altered by metoprolol.Thus, metoprolol was not found to reduce platelet aggregability in healthy male volunteers either at rest or during sympatho-adrenal activation. The effect of treatment may still differ in patients; studies in patients with ischaemic heart disease are under way.     

Integration in trigeminal premotor interneurones in the cat

Seventy-one (n = 71) premotor interneurones have been localized by extracellular recordings within the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract (NVspo-gamma) in nineteen chloralose anaesthetized cats. The neurons were antidromically activated by microstimulation (minimum = 3 microA) applied to the digastric motoneurone subnucleus of the trigeminal motor nucleus. Fifty-one (n = 51) of the interneurones were discharged from the ipsi- and nineteen (n = 19) from the contralateral digastric subnucleus. One neurone out of four tested was antidromically activated from both stimulation sites suggesting a bifurcated axon. The identified premotor neurones had a unique convergence profile of oral and perioral primary afferents. Latency calculations indicated that at least 55% of these interneurones were monosynaptically activated by low stimulus strength applied to the inferior alveolar (minimum = 1.0 T) and/or the lingual nerve (minimum = 1.0 T). The thresholds for evoking the neuronal discharges coincided statistically with those required to evoke a jaw opening reflex response by stimulation of the same nerves. It is suggested that the specific group of NVspo-gamma interneurones under different contexts mediates the disynaptic reflex and participates in the centrally and reflexly evoked "patterning" adjustments of the digastric jaw opening motoneurones during ongoing jaw movements. A companion paper reports the convergence of descending cortical, tectal and ascending cervical inputs, as well as of oro-facial and neck primary afferent inputs onto an unselected population of interneurones in the NVspo-gamma (Westberg and Olsson 1991).     

A COMPARISON BETWEEN AGAR GEL ELECTROPHORESIS and CSF SERUM QUOTIENTS of IgG and ALBUMIN IN NEUROLOGICAL DISEASES

CSF and serum was obtained from 216 patients with neurological or psychoneurotic symptoms and the concentrations of albumin and IgG were immunologically determined. The IgG/albumin index, calculated as the quotient of the CSF/serum ratios of IgG and albumin was compared with electrophoresis on agar gel. In "normal" cases, the IgG/albumin index was between 0.26-0.66. Pathological electrophoresis, i.e. with two or more IgG bands in the gamma globulin region was found in 85 per cent of the MS patients; in 29 per cent of the patients with a possible demyelinating disease; in 41 per cent of patients with CNS infection; and in 4 per cent of patients with other neurological disorders; whereas an increased IgG/albumin index ( greater than 0.66) was found in 88 per cent of the MS patients; in 43 per cent of the patients with a possible demyelinating disease; in 50 per cent of the patients with CNS infection; in 11 per cent of patients with immunological disorders; and in 18 per cent of patients with other neurological diseases. The increase of the IgG/albumin index was sometimes moderate (0.67-0.90), except in patients with MS, syphilis and other CNS infections, where a pathological electrophoresis combined with an IgG/albumin index above 1.0 was found to be a valuable support for the clinical diagnosis.     

Local blood flow regulation in transplanted rat pancreatic islets: influence of adenosine, angiotensin II, and nitric oxide inhibition

BACKGROUND: Transplanted islets lack endothelial cells immediately after implantation and therefore depend on an adequate revascularization for their survival and function. However, the functional properties of the newly formed islet graft microvessels are largely unknown. This study aimed to investigate the blood flow regulation of transplanted pancreatic islets. METHODS: Pancreatic islets were syngeneically transplanted beneath the renal capsule of control and streptozotocin-diabetic rats. Blood flow measurements were performed 4 weeks later using laser-Doppler flowmetry. Adenosine (0.6 mg x kg(-1) x min(-1), angiotensin II (AT II; 0.17 microg x kg(-1) x min(-1)) and the nitric oxide synthase inhibitor NG-nitro-L-arginine (25 mg/ kg) were given to each animal. RESULTS: An increased basal blood flow and basal vascular conductance in the islet grafts, but not in the renal cortex, were seen in diabetic rats compared with control rats. Adenosine increased, and AT II decreased, the vascular conductance of the islet grafts in both nondiabetic and diabetic animals. A more pronounced circulatory response to AT II was observed in kidneys of diabetic animals, whereas there was no difference in the islet graft blood flow response between nondiabetic and diabetic animals. NG-Nitro-L-arginine decreased islet graft blood flow and vascular conductance in both nondiabetic and diabetic recipients, but the effect was more pronounced in the non-diabetic animals. CONCLUSIONS: Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals. However, diabetic animals were less dependent on nitric oxide to maintain a basal blood flow in the islet graft.