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[Synapse density determination in brain structures based on phosphotungstic acid contrast].

Using the E-PTA procedure of Aghajanian and Bloom we determined the numerical density of synapses in the stratum lacunosun-modeculare of the CA1-region in the hippocampus of male albino rats. On this occasion the sources of error both the natural and the methodical were investigated. As natural causes of remarkable scattering and failing correspondence in the findings the individual variability of the synaptic density and the inhomogeneous distribution of synapses must be taken into consideration. Concerning the methodical sources of error the differences in tissue shrinkage become apparent. But faults resulting from applying morphometric methods are the most serious. The counting of synaptic profiles is based on defined morphological criteria. The portion of the synaptic profiles recorded in this way in relation to all those present in the section depends beside other things on the section thickness. Accordingly the correction factors are in correlation with section thickness. The application of the Floderus correction presupposes the determination of the minimum length of the counted profiles. As a result of these investigated the possibilities for reducing the error have been demonstrated.

Animals↗

[Apnea testing to establish death based on brain criteria].

INTRODUCTION: The apnea test provides one of the most important criteria for the diagnosis of death by brain criteria, nevertheless although the absence of spontaneous respiration is a crucial point in the diagnosis of the death, we must point out, that still, there are not standardized criterion to perform this test. DEVELOPMENT: The lack of uniformity at the moment of carrying out this test in our country is due to the use of time as an indirect estimate of the PCO2 levels instead of the actual measurement of the blood level of this gas. This paper reviews the recommendations about this procedure published in the medical literature. It also remarks the most interesting physiopathological aspects related to this test. CONCLUSIONS: At present, the literature does not provide evidence to favor one method over the other however, it seems generally accepted that a positive apnea test requires a level of PCO2 equal or greater than 60 mmHg. Optionally, it is possible to consider 20 mmHg above the starting arterial PCO2 level. It seems clear that this aspect is more important than the duration of the test. The fears about hypoxemic damage during the apnea test are not support by the information found in the literature. It seems that the respiratory like movements do not exclude the diagnosis of death by brain criteria.

Apnea↗

In vivo and in vitro control of acid-base regulation of brain cells during ischemic and selective acidic exposure.

The three-compartment model of brain acid-base regulation postulates that under circumstances of changing function or disease, hydrogen ion concentrations may differ considerably in the interstitial space (ISS), the neurons and the glial cells. During hyperglycemia plus profound ischemia, for example, direct measurements by microelectrodes followed by intracellular HRP staining show that intraglial pH can fall transiently as low as 3.9, although more often the nadir drops to the 4.5-5.5 range. Concurrently, ISS-pH and, by calculation, neuronal pH fails to and remains constant (but not necessarily the same) at pH 6.2. By contrast, during spreading depression, ISS and intraglial pH at first move rapidly and transiently in opposite directions, ISS [H+] rising, intraglial falling. These two then gradually stabilize, whereas neuronal pH remains substantially more steady and near normal, shifting only minimally from resting baseline levels over several minutes' time. Similar but less pronounced effects follow direct electrical stimulation. The net change represents complex biophysical transmembrane and buffering mechanisms that appear to guard neuronal homeostasis. Studies carried out on embryonic rat forebrain neurons and glia show that these cells have considerably different vulnerabilities to extracellular acidity depending on the anionic nature of the acid in the bathing medium. In cultures to which HCI was added to the medium, neurons and neuronal processes almost all survived ten minute exposures to pH 3.8, whereas glial cells succumbed after ten minute exposures at pH not lower than 4.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Transverse anastomoses of the veins at the base of the brain.

Venous anastomoses at the base of the brain are represented by the anterior and posterior communicating veins. The anterior communicating vein anastomoses with the anterior communicating vein anastomoses with the anterior cerebral veins. The posterior communicating veins join the basal veins through the interpenduncular veins. The functional value of these venous anastomoses is less important than that of the arterial polygon of Willis. This anastomotic function depends on anatomical constancy and on the calibre of these transverse veins. Under certain pathological conditions the variations of intracranial pressure result in contralateral venous drainage through these anterior and posterior anastomotic veins.

Brain↗

Reliability of language mapping with magnetic source imaging in epilepsy surgery candidates.

The external validity of a noninvasive language mapping protocol with magnetoencephalography (MEG) has been established through direct comparisons with invasive functional mapping techniques. This study examines the test-retest and interrater reliability of this protocol under realistic testing conditions in 21 epilepsy surgery candidates. Brain activation maps were obtained in the context of an auditory word recognition task and represented by temporally contiguous dipolar activity sources. Both the duration and strength of the associated magnetic flux were used as measures of the magnitude of regional brain activity. Hemispheric asymmetry indices based on these measures showed good interrater reliability and intraparticipant reproducibility. Similar findings were obtained with respect to the location of the geometric center of receptive language-specific cortex (Wernicke's) area in the dominant hemisphere. The results further support the adequacy of this MEG-based brain mapping protocol as a noninvasive tool for receptive language localization in epilepsy surgery candidates.

Adolescent↗

Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy.

We studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 micron in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Adolescent↗

Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation.

OBJECTIVE: To assess the new "Lund therapy" of posttraumatic brain edema, based on principles for brain-volume regulation and improved microcirculation. DESIGN: A prospective, nonrandomized outcome study over a 5-yr period on severely head-injured patients with increased intracranial pressure, comparing the results with a historical control group with the same selection criteria for patients who were treated according to conventional principles. SETTING: General intensive care unit of a university hospital. PATIENTS: Fifty-three consecutive head-injured patients with a Glasgow Coma Score of <8, and with increased intracranial pressure (>25 mm Hg), despite conventional treatment. INTERVENTIONS: Interstitial fluid resorption was obtained by lowering intracapillary hydrostatic pressure, by preserving normal colloid osmotic pressure, and by maintaining a normovolemic (normal albumin/serum and hemoglobin/serum), not overtransfused patient. Intracapillary pressure was reduced by the combination of precapillary vasoconstriction (low-dose thiopental, dihydroergotamine) and reduction of mean arterial pressure, the latter attained with a beta1-antagonist (metoprolol 0.2 to 0.3 mg/kg/24 hrs iv) and an alpha2-agonist (clonidine 0.4 to 0.8 microg/kg x 4 to 6 iv). Clonidine, in combination with normovolemia, also improves microcirculation by reducing catecholamines in plasma. Intracranial blood volume was reduced by arterial (low-dose thiopental sodium and dihydroergotamine) and large-vein (dihydroergotamine) vasoconstriction. The start dose of dihydroergotamine (maximum 0.9 microg/kg/hr) was successively reduced toward discontinuation within 4 to 5 days. MEASUREMENTS AND MAIN RESULTS: There were 8% of patients who died and the neurologic conditions of 13% remained severely damaged, compared with 47% and 11%, respectively, for the control group. CONCLUSIONS: The low mortality compared with previous outcome studies strongly indicates that this therapy improves outcome for severe head injuries. However, a randomized, controlled study is needed to reach general acceptance of this new therapy.

Acute Disease↗

[Brain death, bioethics and organ transplantation].

The concept of death has evolved medically, legally and culturally since the introduction of life support technologies in the middle of the 20th century. The traditional cardiopulmonary and the new neurologically based brain death criterions of death are examined. We conclude that brain death, defined as total and irreversible loss of function of the whole brain, fulfills better "the permanent cessation of functioning of the organism as a whole" definition of death. Brain death diagnosis, based on standard neurologic clinical examination performed accurately, is unequivocal. Transplantation medicine, mostly based on organ donation of brain dead people, has become a routine and universally accepted therapeutic intervention nowadays, which benefits many people. Ethics foundations of organ transplantation are reviewed. Even though brain death and organ donation are widely accepted in medical, legal, religious and public opinion today, the whole society and medical community need to be further educated about these matters, so that unavoidable changes of traditional concepts might be better understood. Permanent education should be the best way to dissipate social fears and distrust towards organ donation and brain death.

Bioethics↗

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study.

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP (n = 21) and c-HSP type (n = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.

Adult↗