Search PubMed⌕ Search

Biomedical subjects

J M Roda

Publications and source records attributed to J M Roda.

At least 19 recordsLinked to original sources
PubMed2006

Thrombolysis and neuroprotection in cerebral ischemia.

Stroke is a major cause of death and disability worldwide. The resulting burden on society grows with the increase in the incidence of stroke. The term brain attack was introduced to describe the acute presentation of stroke and emphasize the need for urgent action to remedy the situation. Though a large number of therapeutic agents, like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or are being evaluated, there is still a large gap between the benefits of these agents and the properties of an ideal drug for stroke. So far, only thrombolysis with rtPA within a 3-hour time window has been shown to improve the outcome of patients with ischemic stroke. Understanding the mechanisms of injury and neuroprotection in these diseases is important to target news sites for treating ischemia. Better evaluation of the drugs and increased similarity between the results of animal experimentation and in the clinical setting requires critical assessment of the selection of animal models and the parameters to be evaluated. Our laboratory has employed a rat embolic stroke model to investigate the combination of rtPA with citicoline as compared to monotherapy alone and investigated whether neuroprotection should be provided before or after thrombolysis in order to achieve a greater reduction of ischemic brain damage.

Animals↗
PubMed2005

Third ventricle glioblastoma. Case report and review of literature.

UNLABELLED: A glioblastoma presenting as a solitary third ventricle mass is exceptional. CASE DESCRIPTION: We report the case of a 29-year-old woman who lost consciousness, was taken to hospital and referred a previous history of depression and diabetes insipidus. Magnetic resonance imaging study revealed a heterogeneous anterior third ventricle mass with ring enhancement after contrast administration. It was approached and subtotally resected by a transcortical-transventricular route and histological diagnosis proved it to be a glioblastoma. There are only two other similar well-described cases and another nine have been previously reported in surgical series of high grade gliomas and glioblastomas. The possible origin of this lesion is discussed.

Adult↗
PubMed2005

Hemangioblastoma of the lateral ventricle: case report and review of the literature.

We report a unique case of hemangioblastoma of the lateral ventricle in a 73 year-old man with cognitive deficits and fluent dysphasia. He harboured an intraventricular tumor, placed at the trigone of the left lateral ventricle. The tumor was successfully excised, by means of a temporal craniotomy. The patient became mute in the immediate postoperative with restoration of speech within a few days. The literature has been reviewed and only three other similar cases have been reported. Discovery of lesions in such unusual location should raise a high degree of suspicion for von Hippel-Lindau disease.

Aged↗
PubMed2004

Intraventricular craniopharyngiomas: topographical classification and surgical approach selection based on an extensive overview.

BACKGROUND: This retrospective study analyzes the clinical, neuroradiological, pathological and surgical characteristics of well-described intraventricular craniopharyngiomas with the aims of: (i) critically to review the criteria used to affirm the diagnosis of an intraventricular location (ii) defining more accurately this topographical diagnosis preoperatively, and (iii) to investigate factors influencing the surgical outcome. METHOD: Clinical, neuroradiological, pathological and surgical objective data of 104 well-described intraventricular craniopharyngiomas (IVC) reported in the literature, in addition to a new case, were analyzed. On the basis of the proofs provided for third ventricle intactness, a new topographical classification for IVC was developed, distinguishing between: (i) strict IVC, with a proved third ventricle floor integrity and (ii) non-strict IVC, without any reliable proof confirming the intactness of the third ventricle floor. Following this classification, clinical features, pathology and surgical outcome for strictly and non-strictly IVC were compared. FINDINGS: For 105 IVC compiled, 36 belonged to the strictly group and 69 to the non-strictly group. Two pathological features were associated with the non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and wider and tighter adherences to third ventricle margins (p=0.01). The non-strict topography was also associated with a worse postoperative outcome (p=0.046). There was a significant relationship between the surgical approach and the final outcome (p=0.05), being the translamina terminalis approach associated with the best outcome. CONCLUSIONS: Two different topographies might be considered among IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider and tighter adhesions to third ventricle boundaries and this subtype is associated with a worse outcome.

Adolescent↗
PubMed2003

Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia.

Cerebral ischemia triggers a multitude of pathophysiological and biochemical events that separately affect the evolution of focal ischemia and, therefore, stroke treatment should logically employ all known neuroprotective agents. We hypothesized that a treatment combining nimodipine and citicoline might have a potential neuroprotective effect. To assess this idea, Sprague-Dawley rats underwent transient bilateral common carotid artery ligation with simultaneous middle cerebral artery occlusion for 60 min. Four treatment groups were established. Animals received either: a) saline (control group); b) intracarotid nimodipine infusion during 30 min in the ischemia-reperfusion (nimodipine group); c) i.p. postischemic citicoline injections once daily for 7 days (citicoline group); or d) intracarotid nimodipine bolus during ischemia-reperfusion plus i.p. postichemic citicoline injections (combination group). They were killed after either 7 or 3 days after reperfusion. In the first case, the volume of the infarcted tissue was studied by a stereological procedure and in the second case, in situ end-labeling of nuclear DNA fragmentation (TUNEL) and Bcl-2 expression were employed to determine the level of apoptosis. The infarct volume was significantly reduced in both the nimodipine and the citicoline treatment groups after 7 days of reperfusion; combination of both drugs produced an additive effect. After 3 days of reperfusion, the number of Bcl-2-positive neurons was significantly increased while that of TUNEL-positive cells significantly decreased at the infarct border in the combined-treatment animals. Our findings demonstrate a neuroprotective effect from an acute single dose of nimodipine during ischemia-reperfusion and prolonged post-ischemic treatment with citicoline in a model of focal cerebral ischemia. These results suggest that a possible mechanism of neuroprotective action would be mediated by increased Bcl-2 expression and decreased apoptosis within the boundary zone of the infarct together with neutralization of the ischemia-reperfusion injury.

Animals↗
PubMed2002

[The role of the extra-intracranial anastomosis and interventionist endovascular therapy in the treatment of complex cerebral aneurysms].

Cerebral revascularization is an useful tool in the treatment of giant or complex cerebral aneurysms that can not be clipped directly by different causes. In turn, interventionist endovascular therapy, an emergent technique with very good results in the treatment of cerebral aneurysms during the last five years, is a new complementary tool to cerebral revascularization for the treatment of complex aneurysms. In the present manuscript we emphasize the beneficial effect of revascularization, followed in a short period of time by the endovascular technique in order to either occlude the parent vessel or to exclude the aneurysm from cerebral circulation. Advantages of this form of therapy, as well as the selection of patients and the present revascularization procedures, are commented.

Aged↗
PubMed2002

[Anatomic and hemodynamic study of anterior communicating artery complex].

Anterior communicating artery complex accounts for the most frequent site of cerebral aneurysms and it is characterized by its great anatomical variability. The development of aneurysms in this complex has been associated with the asymmetry of its afferent vessels. An anatomical and hemodynamic study of the anterior communicating artery was performed. Twenty brain samples obtained from adult necropsies were studied by means of microsurgical dissection. Additionally; 118 cerebral angiographies from patients with spontaneous subarachnoid hemorrhage were studied. A high number of perforanting vessels originated at the anterior communicating artery complex was a relevant finding. The number, distribution and size of these vessels is reported accurately. Analysis of the angiographies showed the association between the existence of an anterior communicating artery aneurysm and the presence of a blood flow predominance through one of the two proximal anterior cerebral arterias.

Cerebral Arteries↗
PubMed2002

Primary hypothalamic-third ventricle lymphoma. Case report and review of the literature.

Primary central nervous system lymphomas (PCNSL) are infrequent tumors and their presentation as a solitary hypothalamic-third ventricle mass can be considered exceptional. We report the case of a 57-year-old woman with progressive visual deterioration, diabetes insipidus and mental confusion. She had a diffuse and homogeneous tumoral lesion involving the third ventricle and the adjacent hypothalamic area with marked enhancement after contrast administration on both, competed tomography scan and magnetic resonance images. It was approached and partially resected by the translamina terminalis route. Histological diagnosis proved to be a diffuse non-Hodgkin lymphoma and the patient subsequently was treated with adjuvant radiotherapy and chemotherapy. Followup examination showed visual acuity recover but persistent confessional state. Eight similar well described cases reported in the literature are reviewed with a description of the major diffenciating features of this neurological entity. Treatment of PCNSL remains a challenge, and the topographical location within the hypothalamic-third ventricle area is even more complex.

Cerebral Ventricle Neoplasms↗
PubMed2001

Cerebral ischemia: from animal studies to clinical practice. Should the methods be reviewed?

The development of experimental models of focal cerebral ischemia has allowed for a better knowledge of its pathophysiology and for testing therapeutic strategies. However, most neuroprotective substances giving favorable results in these models have later not been shown to be clinically effective. This could be explained by several reasons. First, the homogeneity obtained in animal models in order to achieve results is not seen in clinical practice in humans, in whom a given pathological condition may show a high variability depending on several parameters. This makes it difficult to achieve groups of patients sufficiently large and homogeneous to obtain valid conclusions in the clinical trials. The lack of agreement between the experimental studies and the clinical practice can also be explained by other reasons, such as the methods of the experimental model itself; by the fact that the methods to assess results in these models are not comparable to those used in clinical practice; by pathophysiological differences between experimental animals and man, and even by the fact that the substances tested have different pharmacological properties in the different species. These disadvantages must not invalidate preclinical neuroprotection studies. Rather, the knowledge of the reasons for divergences with the clinical situation can help to optimize experimental models so that both become actually comparable, and the laboratory results can be confirmed by clinical studies.

Animals↗
PubMed2000

Nonhistological diagnosis of human cerebral tumors by 1H magnetic resonance spectroscopy and amino acid analysis.

We describe a multivariate analysis procedure to classify human cerebral tumors nonhistologically in vitro, combining the use of 1H magnetic resonance spectroscopy (MRS) with automatic amino acid analysis of biopsy extracts. Eighty-one biopsies were obtained surgically and classified histologically in eight classes: high-grade astrocytomas (class 1, n = 19), low-grade astrocytomas (class 2, n = 10), normal brain (class 3, n = 9), medulloblastomas (class 4, n = 4), meningiomas (class 5, n = 18), metastases (class 6, n = 8), neurinomas (class 7, n = 9), and oligodendrogliomas (class 8, n = 4). Perchloric acid extracts were prepared from every biopsy and analyzed by high resolution 1H MRS and automatic amino acid analysis by ionic exchange chromatography. Intensities of 27 resonances and ratios of resonances were measured in the 1H MRS spectra, and 17 amino acid concentrations were determined in the chromatograms. Linear discriminant analysis provided the most adequate combination of these variables for binary classifications of a biopsy between any two possible classes and in multiple choice comparisons, involving the eight possible classes considered. Correct diagnosis was obtained when the class selected by the computer matched the histological diagnosis. In binary comparisons, consideration of the amino acid profile increased the percentage of correct classifications, being always higher than 75% and reaching 100% in many cases. In multilateral comparisons, scores were: high-grade astrocytomas, 80%; low-grade astrocytomas, 74%; normal brain, 100%; medulloblastomas, 100%; meningiomas, 94.5%; metastases, 86%; neurinomas, 100%; and oligodendrogliomas, 75%. These results indicate that statistical multivariate procedures, combining 1H MRS and amino acid analysis of tissue extracts, provide a valuable classifier for the nonhistological diagnosis of biopsies from brain tumors in vitro.

Algorithms↗
PubMed1999

Hippocampal cell loss in transient global cerebral ischemia in rats: a critical assessment.

The induction of transient global cerebral ischemia by permanent vertebral occlusion and temporary carotid ligation (four-vessel occlusion) is widely accepted as a valid tool for the study of pathogenesis and treatment of ischemia. The neural damage inflicted by this intervention is often assessed by measuring pyramidal cell loss in the CA1 hippocampal field. Nevertheless studies using this model in rats often fail to control variables that are relevant to the outcome, and/or apply biased methods to quantitate histological damage. We have applied unbiased stereological methods to estimate absolute numbers of surviving neurons in CA1 in Wistar rats subjected to either 10 or 20 min global ischemia using the Sugio et al. variant of the original four-vessel occlusion model. Animal mortality was high at both times, with neuron losses averaging 39% and 31%, respectively. Post-operative mortality was reduced substantially by using decompressive craniectomies and, even more effectively, by pre-treating the rats with low doses of phenytoin. Both maneuvers led to a severely increased CA1 neuron loss, which reached 50%, after an ischemia of 10 min. This finding strongly supports that mortality biases the sample. Other noteworthy findings that emerged from this study were a linear relationship between per-ischemic blood pressure increments and animal survival, and a negative correlation between cell survival and preferentially left-sided damage.

Algorithms↗
PubMed1998

Thyroid hormones in human tumoral and normal nervous tissues.

We have studied T4 and T3 concentrations, DNA and protein concentrations and 5' and 5 deiodinases in samples of brain tumors obtained at surgery from 49 patients, and, in most cases, also from surrounding normal tissue. T4 concentrations in normal cortical tissue (6.19+/-0.45 ng/g) were lower than in white matter, but the difference disappeared when referred to the DNA content (2.26+/-0.27 ng/mg DNA). No other differences were found between cortical and white matter, or among cortical lobes. T4 in normal tissue was higher than previously reported, mostly from autopsy samples, whereas T3 (0.99+/-0.07 ng/g) was similar. 5'D-I activity was negligible as compared to 5'D-II (8.11+/-1.09 fmol/h/mg protein). When expressed in relation to the different DNA contents of normal vs. tumoral tissue, 5'D-II activities were the same for both. 5D activity was highly variable in the tumoral tissue, with negligible activities in meningiomas and pituitary adenomas. When referred to the DNA content, T4 and 5'D-II were the same, but T3 concentrations were lower in the tumor (0.24+/-0.03 ng/mg DNA) as compared to normal (0.35+/-0.04 ng/mg DNA) tissue samples. Whether or not this decrease of T3 affects the expression of T3-sensitive processes remains to be studied.

Adolescent↗
PubMed1998

Pattern recognition analysis of 1H NMR spectra from perchloric acid extracts of human brain tumor biopsies.

Pattern recognition techniques (factor analysis and neural networks) were used to investigate and classify human brain tumors based on the 1H NMR spectra of chemically extracted biopsies (n = 118). After removing information from lactate (because of variable ischemia times), unsupervised learning suggested that the spectra separated naturally into two groups: meningiomas and other tumors. Principal component analysis reduced the dimensionality of the data. A back-propagation neural network using the first 30 principal components gave 85% correct classification of meningiomas and nonmeningiomas. Simplification by vector rotation gave vectors that could be assigned to various metabolites, making it possible to use or to reject their information for neural network classification. Using scores calculated from the four rotated vectors due to creatine and glutamine gave the best classification into meningiomas and nonmeningiomas (89% correct). Classification of gliomas (n = 47) gave 62% correct within one grade. Only inositol showed a significant correlation with glioma grade.

Biomarkers, Tumor↗
PubMed1998

Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Even though the utilization of substrates alternative to glucose may play an important role in the survival of brain cells under ischemic conditions, evidence on changes in substrate selection by the adult brain in vivo during ischemic episodes remains very limited. This study investigates the utilization of glutamate, glutamine, and GABA as fuel by the neuronal and glial tricarboxylic acid cycles of both cerebral hemispheres after partially reversible focal cerebral ischemia (FCI). METHODS: Right hemisphere infarct was induced in adult Long-Evans rats by permanent occlusion of the right middle cerebral artery and transitory occlusion of both common carotid arteries. (1,2-13C2) acetate was infused for 60 minutes in the right carotid artery immediately after carotid recirculation had been re-established (1-hour group) or 23 hours later (24-hour group). Extracts from both cerebral hemispheres were prepared and analyzed separately by 13C nuclear magnetic resonance and computer-assisted metabolic modeling. RESULTS: FCI decreased the oxidative metabolism of glucose in the brain in a time-dependent manner. Reduced glucose oxidation was compensated for by increased oxidations of (13C) glutamate and (13C) GABA in the astrocytes of the ipsilateral hemispheres of both groups. Increased oxidative metabolism of (13C) glutamine in the neurons was favored by increased activity of the neuronal pyruvate recycling system in the 24-hour group. CONCLUSIONS: Data were obtained consistent with time-dependent changes in the utilization of glutamate and GABA or glutamine as metabolic substrates for the glial or neuronal compartments of rat brain after FCI.

Acetates↗
PubMed1998

[Autonomic and metabolic sequelae of global and focal cerebral ischemia in an experimental model].

INTRODUCTION: During the last decades the influence of cerebrovascular disease on heart and autonomic nervous system has been studied in numerous reports. Autonomic and metabolic changes have been described during brain ischemia. METHODS: We studied some parameters and its modifications during global (GBI) and focal brain ischemia (FBI). Ten Wistar rats were subjected to global ischemia and eleven to focal brain ischemia, during 20 and 90 minutes followed in both cases by reperfusion. Mean blood pressure, heart rate and glycaemia before, during and after brain ischemia were registered. pH, pO2 and pCO2 were maintained within normal range using endovenous tamponed solutions. RESULTS: During GBI the blood pressure rose and returned to normal in the reperfusion period. Heart rate decreased in both stroke models and hyperglycaemia was present from the beginning in two groups. CONCLUSIONS: GBI and FBI bring about autonomic changes as increased mean blood pressure (only in GBI) and decreased heart rate; probably these might be explained by an autonomic nervous system disorder or by intracranial hypertension. Hyperglycaemia could be related to cathecholamines secretion. These effects might influence in the pathophysiology of brain ischemia.

Animals↗
PubMed1998

[Treatment of embolic cerebral infarct via thrombolysis and cytoprotection with U-74389-G in rats].

INTRODUCTION: The best treatment for cerebral ischemic will probably comprise the association of inhibition of ischemia-reperfusion injury mediators and early reperfusion. OBJECTIVE: We tried to demonstrate if reperfusion by thrombolysis (rt-PA) and free radical scavenging (U-74389-G) reduces ischemic-reperfusion cerebral injury in a rat model of embolic brain infarction. MATERIAL AND METHODS: 39 female Long Evans rats were embolized in right hemisphere with an autologous clot. Three groups are considered; A: control (n = 15), B: rt-PA i.v., 20 mg/kg starting 90-120 minutes after embolization (n = 15), C: rt-PA, same dose, and U-74389-G i.v., 3 mg/kg before and after embolization (n = 9). Arterial blood pressure, gasometry, glycemia and temperature were controlled. Volume of cerebral lesion in surviving animals 24 hours was measured. Autopsy was performed to verify the cause of death in rats which died. RESULTS: Mortality: group A: 8/15; group B: 9/15; group C: 8/9. Early death was related to cerebral injury except for five rats which developed peritoneal bleeding. We found severe acidosis in rats from group C. Differences in mean volume of ischemic lesion in group A and B are nosignificant despite a tendency to a reduction after thrombolysis. CONCLUSIONS: In this model thrombolysis alone and in association with U-74389-G failed to reduce cerebral lesion and mortality.

Animals↗