Stereotactic coordinates for intracerebroventricular infusion after permanent focal cerebral ischemia in Wistar rats.

BACKGROUND: Intracerebroventricular (ICV) experimental route is highly promising due to immediate approach of a "therapy" to the cerebrospinal compartment. Ischemic edema causes structural dislocations and stereotaxia alterations after temporary Middle Cerebral Artery Occlusion (t-MCAO), while there is no similar study for intracerebroventricular (ICV) invasion after permanent MCAO (p-MCAO). METHODS: Male Wistar rats were subjected to right p-MCAO and clinically evaluated 6 and 18 hours post-occlusion, using the modified Neurological Stroke Scale (mNSS) and modified Bederson's Scale (mBS). Infarction volume, hemispheric edema, middle line dislocation and stereotaxia of the lateral ventricles were studied at the same time-points. RESULTS: P-MCAO induced mild but significant changes in the stereotaxia of the infarcted (ipsilateral) lateral ventricle on 18- (P<0.05), though not 6-hours (P>0.05) post-occlusion. These changes correlated with the mNSS and mBS scores (P<0.01) and allowed the expression of linear mathematical equations (stereotaxic coordinate = b0 + b1*mNSS; calculated by regression analysis) predicting the new ventricular position in each individual animal. The contralateral ventricular system was structurally unaffected on both time-points. Verification experiments indicated that the new coordinates were necessary on 18-hours post-occlusion for successful ICV invasion in all p-MCAO rats (Number Needed to Treat 2.28), compared to 56.25% success when using the classical coordinates for normal rats. CONCLUSION: P-MCAO causes relatively late but predictable stereotaxia shifts for ICV invasion, which are different compared to t-MCAO.

Predictable ventricular shift after focal cerebral ischaemia in rats: practical considerations for intraventricular therapeutic interventions.

Intracerebroventricular (ICV) route of administration is a useful experimental method to study the effects of chemicals or cellular grafts in the ventricular compartment of the brain after focal ischaemia. However, the induced oedema may cause structural dislocating phenomena and render a stereotaxic ICV invasion difficult and practically unavailable especially during the acute post-ischaemia phase. The aim of this study was to measure these structural ventricular dislocations and set new stereotaxic coordinates for successful and cost-effective ICV invasion 6-18 h after focal cerebral ischaemia. Wistar rats were subjected to 2 h middle cerebral artery occlussion (t-MCAO), were neurologically evaluated (modified Neurological Stroke Scale [mNSS], modified Bederson's Scale [mBS] and grid-walking test [GWT]) and brain slides were studied at 6 and 18 h post-occlusion for infarction volume, hemispheric oedema, middle line dislocation and stereotaxia of the lateral ventricles. Our data indicated that stereotaxic coordinates of the lateral ventricles in the infarcted and contralateral hemispheres significantly (P < 0.05) changed at both time-points and were linearly correlated with the mNSS, mBS and some GWT scores (P < 0.001). This correlation allowed for the calculation of simple (linear) mathematical equations (stereotaxic coordinate = b0 + b1*mNSS, where 'b0' and 'b1' are fixed number and factor, respectively, calculated by regression analysis) that determined individually new coordinates for each animal. Verification experiments revealed that the new coordinates render ICV invasion feasible in up to 80% of infarcted rats (number needed to treat 1.65), compared with only 19.4% using the classical coordinates for normal rats. Therefore, we propose a new, time- and cost-effective methodology for practically feasible ICV invasion in rats 6-18 h after t-MCAO.

Is there or is there not a place for anti-interferon antibodies in the decision making of multiple sclerosis treatment optimisation?

Several factors contribute to the fact that not all multiple sclerosis (MS) patients respond equally well to long-term interferon beta (IFNbeta) treatment, even if the initial response is adequate. Among these factors, anti-interferon neutralising antibodies (NAbs) may be included. There is increasing evidence that these antibodies have a clinical impact in MS treated patients, which is evident some months following the initiation of treatment with IFN?. Several efforts to reduce the concentration of NAbs, especially when they are in high titres and clinically active, have failed. However, the same efforts may be more effective if applied following early detection of the antibodies, thus leading to a continuation of the initially selected interferon treatment.

On the significance and reproducibility of the fragmentation of the Golgi apparatus of motor neurons in human spinal cords.

Recent immunocytochemical and morphometric studies with an organelle-specific antiserum against MG-160, an intrinsic membrane sialoglycoprotein of the Golgi apparatus, have shown in several patients with sporadic amyotrophic lateral sclerosis (ALS), and in a few patients with related conditions, a fragmentation of the Golgi apparatus of spinal cord motor neurons which resembles the dispersion of the organelle observed in cells treated with microtubule depolymerizing agents. In the present study we examined by morphometry the effect of tissue fixation and processing on the immunocytochemical morphology of the Golgi apparatus of motor neurons from spinal cords of five controls and in one patient with leptomeningeal lymphoma. Qualitative studies of the Golgi apparatus of spinal cord motor neurons were also carried out in two more individuals with lymphoma or leukemia with leptomeningeal involvement and in one patient with multiple myeloma associated with a chronic inflammatory demyelinating polyneuropathy. The results of this study show that it is possible to obtain optimal immunocytochemical preparations of the Golgi apparatus of spinal cord motor neurons in routinely fixed and processed tissues obtained at autopsy. This study also provides baseline values of the Golgi apparatus in normal individuals which may be useful in future studies of the organelle in human neuropathologic conditions affecting the lower motor neuron unit. Lastly, this study shows that the fragmentation of the neuronal Golgi apparatus is not limited to ALS and related disorders.

A contribution to the pathogenesis of respiratory disturbances associated with subarachnoid haemorrhage; an experimental approach using an animal model.

The present experimental work focuses on the mechanisms involved in respiratory distress observed in the course of subarachnoid haemorrhage. For this purpose, respiratory disturbances were induced in rabbits by injecting fresh autologous blood into the subarachnoid space. For six hours after this artificially induced SAH, blood PO2 and PCO2 as well as expiratory air CO2 were regularly determined, while during the same period cerebral blood flow and cerebrospinal fluid pressure measurements were recorded. The results of this study suggest that pressure effects acting the brain structures that support respiration are principally involved in the pathogenesis of respiratory disturbances following SAH. A decrease in CBF and hypoxia with hypercapnia play a contributing secondary role adding to a vicious cycle phenomenon.

Malignant pineocytoma with prominent papillary features.

A pineal gland tumor in a 57-year-old man proved to be lethal within six months despite radiotherapy. The tumor was demonstrated to be a pineocytoma at autopsy but it was unusual is that papillary structures constituted a prominent component of it. We report that papillary features may be a component of pineocytic neoplasms and that they may have prognostic significance. Papillary pineal parenchymal neoplasms should be distinguished from other benign and malignant papillary neoplasms which also occur in the pineal region.

Immunocytochemical study of the glial fibrillary acidic protein in human neoplasms of the central nervous system.

The distribution of the glial fibrillary acidic protein (GFAP) was investigated in sections of 131 paraffin-embedded brain neoplasms obtained at surgery or at autopsy. The unlabeled antibody immunoperoxidase (peroxidase-antiperoxidase, PAP) method was used. Equally good results were obtained from 17-year-old material and from recent material derived at surgery or autopsy and fixed with Bouin fluid or phosphate-buffered formalin. The perikaryons and processes of reactive astrocytes showed the most intense stain for GFAP. Positive reaction to antibody against GFAP of varying intensity was demonstrated in astrocytomas of various grades of malignancy (32 of 32), glioblastoma multiforme (10 of 10), subependymal giant cell astrocytoma (1 of 1), ependymoma (2 of 10), subependymoma (4 of 4), and astrocytes in mixed neoplasms (8 of 8). In two neoplasms diagnosed as malignant astrocytomas and in four neoplasms diagnosed as glioblastoma multiforme, GFAP stain was limited to a few neoplastic cells. Usually the stain was more intense over processes than in perikaryons, with the exception of gemistocytic astrocytomas and the giant cells in glioblastoma multiforme, which showed an equally intense stain over perikaryons and processes. The periphery of Rosenthal fibers was intensely positive for GFAP. In astrocytic neoplasms the number of GFAP-positive cells and the intensity of the stain were inversely proportional to the degree of malignancy. In the following neoplasms the reaction for GFAP was negative: oligodendroglioma (3), oligodendroblastoma (1), medulloblastoma (3), medulloepithelioma (1), neuroblastoma (1), pineocytoma (1), typical teratoma of the pineal (1), fibrosarcoma (1), pituitary adenoma (2), craniopharyngioma (1), chordoma (1), chemodectoma of globus jugulare (1), metastatic carcinoma (17), and lymphoma (8). In one of 18 meningiomas, endogenous peroxidase activity was seen in mast cells. All meningiomas studied were negative for GFAP. In one of six neurinomas a positive reaction for GFAP was detected over processes. The authors concluded that the immunostain for GFAP is useful in the diagnoses of astrocytic neoplasms and of mixed gliomas.