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PubMed2024

Repeated evolution on oceanic islands: comparative genomics reveals species-specific processes in birds.

Understanding the interplay between genetic drift, natural selection, gene flow, and demographic history in driving phenotypic and genomic differentiation of insular populations can help us gain insight into the speciation process. Comparing patterns across different insular taxa subjected to similar selective pressures upon colonizing oceanic islands provides the opportunity to study repeated evolution and identify shared patterns in their genomic landscapes of differentiation. We selected four species of passerine birds (Common Chaffinch Fringilla coelebs/canariensis, Red-billed Chough Pyrrhocorax pyrrhocorax, House Finch  Haemorhous mexicanus and Dark-eyed/island Junco Junco hyemalis/insularis) that have both mainland and insular populations. Changes in body size between island and mainland populations were consistent with the island rule. For each species, we sequenced whole genomes from mainland and insular individuals to infer their demographic history, characterize their genomic differentiation, and identify the factors shaping them. We estimated the relative (Fst) and absolute (dxy) differentiation, nucleotide diversity (π), Tajima's D, gene density and recombination rate. We also searched for selective sweeps and chromosomal inversions along the genome. All species shared a marked reduction in effective population size (Ne) upon island colonization. We found diverse patterns of differentiated genomic regions relative to the genome average in all four species, suggesting the role of selection in island-mainland differentiation, yet the lack of congruence in the location of these regions indicates that each species evolved differently in insular environments. Our results suggest that the genomic mechanisms involved in the divergence upon island colonization-such as chromosomal inversions, and historical factors like recurrent selection-differ in each species, despite the highly conserved structure of avian genomes and the similar selective factors involved. These differences are likely influenced by factors such as genetic drift, the polygenic nature of fitness traits and the action of case-specific selective pressures.

Animals↗
PubMed2006

Nonequilibrium molecular dynamics simulation study on the orientation transition in the amphiphilic lamellar phase under shear flow.

By the extensive large-scale nonequilibrium molecular dynamics simulation on an effective generic model-A2B2 tetramer for amphiphiles, we investigate the shear-induced parallel to perpendicular orientation transition in the lamellar phase as a function of segregation degree and shear rate. Under low rate shear flow the evolution of parallel lamellar configurations at different segregation strengths shows a similar kinetic pathway independent of the segregation degree. While under high rate shear flow in which the lifetime of undulation instability exceeds the characteristic time of the applied shear flow, the kinetic pathway of the shear-induced parallel-to-perpendicular orientation transition in lamellar systems is the segregation degree dependent. Comparing the temporal mesoscopic domain morphology, the microscopic chain conformation, and macroscopic observable-viscosity changes with the experimentally proposed mechanisms, we find that the undulation instability, partial breakup of monodomain, grain rotation, and recombination combined with defect migration and annihilation are the kinetic pathway for the parallel-to-perpendicular orientation transition in the lamellar phase in or near the intermediate segregation limit, and that the undulation instability, domain dissolution, and reformation along the preferred direction combined with defect migration and annihilation are the kinetic pathway for the parallel-to-perpendicular orientation transition in the lamellar phase close to the order-to-disorder phase transition point. A detailed underlying microscopic picture of the alignment process illustrates that the orientation transition is driven by the alignment of molecules with shear flow. The orientation diagram that characterizes the steady-state orientations as a function of shear rate and attractive potential depth is built, in which the attractive potential depth takes the role of an inverse temperature, somewhat like the Flory-Huggins interaction parameter. The microscopic mechanism of the critical orientation transition condition is discussed.

Journal Article↗
PubMed2006

Site-specific genetic divergence in parallel hybrid zones suggests nonallopatric evolution of reproductive barriers.

The evolution of reproductive isolation in the presence of gene flow is supported by theoretical models but rarely by data. Empirical support might be gained from studies of parallel hybrid zones between interbreeding taxa. We analysed gene flow over two hybrid zones separating ecotypes of Littorina saxatilis to test the expectation that neutral genetic markers will show site-specific differences if barriers have evolved in situ. Distinct ecotypes found in contrasting shore habitats are separated by divergent selection and poor dispersal, but hybrid zones appear between them. Swedish islands formed by postglacial uplift 5000 years ago provide opportunities to assess genetic structure in a recently evolved system. Each island houses a discrete population containing subpopulations of different ecotypes. Hybrid zones between ecotypes may be a product of ecological divergence occurring on each island or a consequence of secondary overlap of ecotypes of allopatric origin that have spread among the islands. We used six microsatellite loci to assess gene flow and genetic profiles of hybrid zones on two islands. We found reduced gene flow over both hybrid zones, indicating the presence of local reproductive barriers between ecotypes. Nevertheless, subpopulations of different ecotypes from the same island were genetically more similar to each other than were subpopulations of the same ecotype from different islands. Moreover, neutral genetic traits separating the two ecotypes across hybrid zones were site-specific. This supports a scenario of in situ origin of ecotypes by ecological divergence and nonallopatric evolution of reproductive barriers.

Animals↗
PubMed2004

The genetic architecture of parallel armor plate reduction in threespine sticklebacks.

How many genetic changes control the evolution of new traits in natural populations? Are the same genetic changes seen in cases of parallel evolution? Despite long-standing interest in these questions, they have been difficult to address, particularly in vertebrates. We have analyzed the genetic basis of natural variation in three different aspects of the skeletal armor of threespine sticklebacks (Gasterosteus aculeatus): the pattern, number, and size of the bony lateral plates. A few chromosomal regions can account for variation in all three aspects of the lateral plates, with one major locus contributing to most of the variation in lateral plate pattern and number. Genetic mapping and allelic complementation experiments show that the same major locus is responsible for the parallel evolution of armor plate reduction in two widely separated populations. These results suggest that a small number of genetic changes can produce major skeletal alterations in natural populations and that the same major locus is used repeatedly when similar traits evolve in different locations.

Alleles↗
PubMed2003

Parallel changes in gene expression after 20,000 generations of evolution in Escherichiacoli.

Twelve populations of Escherichia coli, derived from a common ancestor, evolved in a glucose-limited medium for 20,000 generations. Here we use DNA expression arrays to examine whether gene-expression profiles in two populations evolved in parallel, which would indicate adaptation, and to gain insight into the mechanisms underlying their adaptation. We compared the expression profile of the ancestor to that of clones sampled from both populations after 20,000 generations. The expression of 59 genes had changed significantly in both populations. Remarkably, all 59 were changed in the same direction relative to the ancestor. Many of these genes were members of the cAMP-cAMP receptor protein (CRP) and guanosine tetraphosphate (ppGpp) regulons. Sequencing of several genes controlling the effectors of these regulons found a nonsynonymous mutation in spoT in one population. Moving this mutation into the ancestral background showed that it increased fitness and produced many of the expression changes manifest after 20,000 generations. The same mutation had no effect on fitness when introduced into the other evolved population, indicating that a mutation of similar effect was present already. Our study demonstrates the utility of expression arrays for addressing evolutionary issues including the quantitative measurement of parallel evolution in independent lineages and the identification of beneficial mutations.

Biological Evolution↗
PubMed1950

Studies on entry and egress of poliomyelitis infection. II. Entry and spread after exposure of the trigeminal nerve.

Direct exposure to poliomyelitis virus of the central end of a cut branch of the V cranial nerve was followed by centripetal spread of infection to the semilunar (Gasserian) ganglion, involvement of which was detected both histologically and by subinoculation as early as the 3rd day. In some instances infection did not progress further; in others it spread into the CNS with initial involvement of the trigeminal centers in the pons and medulla as early as the 4th day and by the 5th day was further advanced but still limited to the brainstem. Once infection was established it progressed both rostrally and caudally, at times with great rapidity, through the brainstem and reached the cord on the 6th or a later day. Incidental exposure in traumatized muscle of peripheral fibers of the VII motor nerve led in some instances to spread along that pathway directly into the CNS. Application of the experimental results to human poliomyelitis is of interest chiefly in four respects. (1) The ascent of infection from a peripheral ganglion of the head area to the CNS with initial encephalitis of the brainstem and subsequent descent to the spinal cord is believed to parallel the evolution of the human disease as suggested by the character and order of development of the early symptoms and signs. (2) The failure in some instances of infection to spread from an infected peripheral ganglion to the CNS may parallel inapparent ("subclinical") poliomyelitis in man. (3) Invasion of virus through traumatized muscle directly to the CNS also has possible analogues in human experience which will be discussed in a later paper. (4) The presence of well marked and sometimes extensive lesions in the brainstem one or more days before symptoms emerge is also believed to parallel the human case.

Encephalitis↗
PubMed2000

The evolution of sex differences in language, sexuality, and visual-spatial skills.

The evolutionary neurological and physical foundations for human sex differences in language, sexuality, and visual spatial skills are detailed and primate and human studies are reviewed. Trends in the division of labor were established early in evolution and became amplified with the emergence of the "big brained" Homo erectus. A bigger brain necessitated a size increase in the birth canal and female pelvis. These and other physical changes, e.g., the swelling of the breasts and buttocks, may have paralleled the evolution of full-time sexual receptivity, the establishment of the home base, and exaggerated sex differences in the division of labor (hunting vs. gathering), which in turn promoted innate sex differences in visual spatial vs. language skills. For example, female primates produce more social and emotional vocalizations and engage in more tool use and gathering activities, whereas males tend to hunt and kill. Similar labor divisions are evident over the course of human evolution. "Woman's work" such as child rearing, gathering, and domestic tool construction and manipulation contributed to the functional evolution of Broca's speech area and the angular gyrus--which injects temporal sequences and complex concepts into the stream of language and thought. These activities gave rise, therefore, to a female superiority in grammatical (temporal sequential) vocabulary-rich language. Hunting as a way of life does not require speech but requires excellent visual-spatial skills and, thus, contributed to a male visual-spatial superiority and sex difference in the brain. Over the course of evolution males acquired modern human speech through genetic inheritance and because they had mothers who taught them language.

Affect↗
PubMed2006

Monitoring the acute phase response in non-immediate allergic drug reactions.

PURPOSE OF REVIEW: The aim of this article is to evaluate the advantages of monitoring the immunological response of non-immediate allergic drug reactions in parallel with the affected tissues, skin and peripheral blood, in order to improve our understanding of the immunological response. RECENT FINDINGS: Several studies have shown that in the skin and peripheral blood, the agents that take part in the development of the immunological reaction express a number of markers that parallel the evolution of the disease process. These markers include cytokines, chemokines, and cytotoxic factors, as well as many other markers involved in such mechanisms as drug metabolism and signal transduction. SUMMARY: Monitoring the acute phase response to a drug in the skin with parallel studies in the blood provides clues that increase our understanding of the underlying pathological mechanisms in adverse reactions to drugs with an immunological basis. This approach, together with molecular biology techniques such as microarrays and genomic studies may be useful in future, in better characterizing the clinical subtype and prognosis of nonimmediate allergic drug reactions and generating targeted treatment regimens.

Acute-Phase Reaction↗
PubMed1994

Bioenergetics: the evolution of molecular mechanisms and the development of bioenergetic concepts.

Possible routes for the evolution of cell energetics are considered. It is assumed that u.v. light was the primary energy source for the precursors of the primordial living cell and that primitive energetics might have been based on the use of the adenine moiety of ADP as the u.v. chromophore. It is proposed that the excitation of the adenine residue facilitated phosphorylation of its amino group with subsequent transfer of a phosphoryl group to the terminal phosphate of ADP to form ATP. ATP-driven carbohydrate synthesis is considered as a mechanism for storing u.v.-derived energy, which was then used in the dark. Glycolysis presumably produced compounds like ethanol and CO2, which easily penetrate the membrane and therefore were lost by the cell. Later lactate-producing glycolysis appeared, the end product being non-penetrant and, hence, retained inside the cell to be utilized to regenerate carbohydrates when light energy became available. Production of lactate was accompanied by accumulation of equimolar H+. To avoid acidification of the cell interior, an F0-type H+ channel was employed. Later it was supplemented with F1. This allowed the ATP energy to be used for 'uphill' H+ pumping to the medium, which was acidified due to glycolytic activity of the cells. In the subsequent course of evolution, u.v. light was replaced by visible light, which has lower energy but is less dangerous for the cell. It is assumed that bacteriorhodopsin, a simple and very stable light-driven H+ pump which still exists in halophilic and thermophilic Archaea, was the primary system utilizing visible light. The delta mu-H+ formed was used to reverse the H(+)-ATPase, which began to function as H(+)-ATP-synthase. Later, bacteriorhodopsin photosynthesis was substituted by a more efficient chlorophyll photosynthesis, producing not only ATP, but also carbohydrates. O2, a side product of this process, was consumed by the H(+)-motive respiratory chain to form delta mu-H+ in the dark. At the next stage of evolution, a parallel energy-transducing mechanism appeared which employed Na+ instead of H+ as the coupling ion (the Na+ cycle).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine↗
PubMed2005

Conserved synteny between the Ciona genome and human paralogons identifies large duplication events in the molecular evolution of the insulin-relaxin gene family.

The aims of the study were to outline the sequence of events that gave rise to the vertebrate insulin-relaxin gene family and the chromosomal regions in which they reside. We analyzed the gene content surrounding the human insulin/relaxin genes with respect to what family they belonged to and if the duplication history of investigated families parallels the evolution of the insulin-relaxin family members. Markov Clustering and phylogenetic analysis were used to determine family identity. More than 15% of the genes belonged to families that have paralogs in the regions, defining two sets of quadruplicate paralogy regions. Thereby, the localization of insulin/relaxin genes in humans is in accordance with those regions on human chromosomes 1, 11, 12, 19q (insulin/insulin-like growth factors) and 1, 6p/15q, 9/5, 19p (insulin-like factors/relaxins) were formed during two genome duplications. We compared the human genome with that of Ciona intestinalis, a species that split from the vertebrate lineage before the two suggested genome duplications. Two insulin-like orthologs were discovered in addition to the already described Ci-insulin gene. Conserved synteny between the Ciona regions hosting the insulin-like genes and the two sets of human paralogons implies their common origin. Linkage of the two human paralogons, as seen in human chromosome 1, as well as the two regions hosting the Ciona insulin-like genes suggests that a segmental duplication gave rise to the region prior to the genome doublings. Thus, preserved gene content provides support that genome duplication(s) in addition to segmental and single-gene duplications shaped the genomes of extant vertebrates.

Amino Acid Sequence↗
PubMed1986

Evolution of cell and chromosome structure in eukaryote.

The analysis of the data so far available indicates that eukaryotic chromosome with splicing characteristics appeared quite early in evolution possibly parallel and not sequential to the prokaryotic system. The endosymbiotic origin of the eukaryotic cell involved a primitive undifferentiated unicellular eukaryote and a photosynthetic or non-photosynthetic microbe. Certain regulatory genes of extra-cellular organelles were transferred later through molecular hybridization to the nucleus. The evolution of multicellularity and sexual reproduction led to the origin of innumerable eukaryotic forms in the late precambrian period. This new concept of the author can account for the evolution of complex eukaryotic chromosome and harmonious functioning of extra-cellular organelles with the nucleus. The concept also explains the sudden spurt of innumerable eukaryotic fossils at the early palaeozoic era.

Animals↗
PubMed1979

[Symptomatic arterial hypertension in lupus nephropathy].

Sixty six patients with lupus nephropathy with hypertonic syndrome are examined. In patients with latent (inactive) lupus glomerulonephritis hypertonic syndrome developed 3--8 months after the initiation of the corticosteroid treatment, advancing with fluctuations, in some of the patients the arterial pressure being normalized after the discontinuation of that treatment. In patients with chronic active lupus glomerulonephritis without nephrotic syndrome, the hypertension develops before the initiation of the corticosteroid treatment, fluctuating at the beginning, and gradually assumes a stable character 3--5 months after the beginning of such treatment, sometimes with a malignant course and rapid development of renal insufficiency. The hypertonic syndrome advances most severely and malignantly in chronic lupus glomerulonephritis with nephrotic syndrome and is resistant to the active antihypertensive treatment. In 18, out of 25, such patients, the hypertonic syndrome is manifested in parallel with nephropathy before the inclusion of the cortocosteroid treatment. The grave and malignant course of the hypertonic syndrome is associated with the peculiarities of the clinical form and histomorphological type of that lupus nephropathy. In the patients with nephrosclerosis, the hypertonic syndrome is with a gradually progressing evolution, in parallel with the progress of the renal insufficiency.

Adolescent↗
PubMed1983

[Characteristics of testosterone binding to plasma proteins during the sexual cycle in a seasonally-reproductive animal, the male viviparous lizard].

Plasma testosterone binding activity was determined by an equilibrium dialysis method in the male of Lacerta vivipara during the annual cycle of activity (from March to September). Capacity showed significant variations during the sexual cycle although affinity remained constant. The variations of capacity were then compared with plasma testosterone levels measured by radioimmunoassay and plasma proteins content measured by the Lowry method. The three parameters showed parallel seasonal evolution except in May-June when binding activity increased although plasma testosterone and protein levels fell. The physiological meaning of this conspicuous phenomenon is discussed=an active mechanism of strengthening of the atrophy of accessory sexual organs is hypothesized. Furthermore, the increase of the binding activity which occurs in autumn and is parallel to the levels of testosterone must prevent these accessory organs from a full resumption of activity before the retreat since the lizard is a hibernating animal. These results emphasize the key role played by specific plasma binding proteins in the modulation of steroid hormone action.

Animals↗
PubMedDate not supplied

Translation initiation: structures, mechanisms and evolution.

Translation, the process of mRNA-encoded protein synthesis, requires a complex apparatus, composed of the ribosome, tRNAs and additional protein factors, including aminoacyl tRNA synthetases. The ribosome provides the platform for proper assembly of mRNA, tRNAs and protein factors and carries the peptidyl-transferase activity. It consists of small and large subunits. The ribosomes are ribonucleoprotein particles with a ribosomal RNA core, to which multiple ribosomal proteins are bound. The sequence and structure of ribosomal RNAs, tRNAs, some of the ribosomal proteins and some of the additional protein factors are conserved in all kingdoms, underlying the common origin of the translation apparatus. Translation can be subdivided into several steps: initiation, elongation, termination and recycling. Of these, initiation is the most complex and the most divergent among the different kingdoms of life. A great amount of new structural, biochemical and genetic information on translation initiation has been accumulated in recent years, which led to the realization that initiation also shows a great degree of conservation throughout evolution. In this review, we summarize the available structural and functional data on translation initiation in the context of evolution, drawing parallels between eubacteria, archaea, and eukaryotes. We will start with an overview of the ribosome structure and of translation in general, placing emphasis on factors and processes with relevance to initiation. The major steps in initiation and the factors involved will be described, followed by discussion of the structure and function of the individual initiation factors throughout evolution. We will conclude with a summary of the available information on the kinetic and thermodynamic aspects of translation initiation.

Biophysical Phenomena↗
PubMed2004

Phylogenetics of artificial manuscripts.

Biological evolution has parallels with the development of natural languages, man-made artifacts, and manuscript texts. As a result, phylogenetic methods developed for evolutionary biology are increasingly being used in linguistics, anthropology, archaeology, and textual criticism. Despite this popularity, there have been few critical tests of their suitability. Here, we apply phylogenetic methods to artificial manuscripts with a known true phylogeny, produced by modern 'scribes'. Although the survival of ancestral forms and multiple descendants from a single ancestor are probably much more common in manuscript evolution than biological evolution, we were able to reconstruct most of the true phylogeny. This is important because phylogenetic methods are influencing the production of critical editions of major written works. We also show that the variation in rates of change at different locations in the text follows a gamma distribution, as is often the case in DNA sequences.

Language↗
PubMed2001

Thoughts on the development, structure and evolution of the mammalian and avian telencephalic pallium.

Various lines of evidence suggest that the development and evolution of the mammalian isocortex cannot be easily explained without an understanding of correlative changes in surrounding areas of the telencephalic pallium and subpallium. These are close neighbours in a common morphogenetic field and are postulated as sources of some cortical neuron types (and even of whole cortical areas). There is equal need to explain relevant developmental evolutionary changes in the dorsal thalamus, the major source of afferent inputs to the telencephalon (to both the pallium and subpallium). The mammalian isocortex evolved within an initially small dorsal part of the pallium of vertebrates, surrounded by other pallial parts, including some with a non-cortical, nuclear structure. Nuclear pallial elements are markedly voluminous in reptiles and birds, where they build the dorsal ventricular ridge, or hypopallium, which has been recently divided molecularly and structurally into a lateral pallium and a ventral pallium. Afferent pallial connections are often simplified as consisting of thalamic fibres that project either to focal cell aggregates in the ventral pallium (predominant in reptiles and birds) or to corticoid areas in the dorsal pallium (predominant in mammals). Karten's hypothesis, put forward in 1969, on the formation of some isocortical areas postulates an embryonic translocation into the nascent isocortex of the ventropallial thalamorecipient foci and respective downstream ventropallial target populations, as specific layer IV, layers II- III, or layers V-VI neuron populations. This view is considered critically in the light of various recent data, contrasting with the alternative possibility of a parallel, separate evolution of the different pallial parts. The new scenario reveals as well a separately evolving tiered structure of the dorsal thalamus, some of whose parts receive input from midbrain sensory centres (collothalamic nuclei), whereas other parts receive oligosynaptic 'lemniscal' connections bypassing the midbrain (lemnothalamic nuclei). An ampler look into known hodological patterns from this viewpoint suggests that ancient collothalamic pathways, which target ventropallial foci, are largely conserved in mammals, while some emergent cortical connections can be established by means of new collaterals in some of these pathways. The lemnothalamic pathways, which typically target ancestrally the dorsopallial isocortex, show parallel increments of relative size and structural diversification of both the thalamic cell populations and the cortical recipient areas. The evolving lemnothalamic pathways may interact developmentally with collothalamic corticopetal collaterals in the modality-specific invasion of the emergent new areas of isocortex.

Animals↗
PubMed1985

[Angiolymphoid hyperplasia with eosinophilia. Extensive form associated with thrombopenic purpura].

The authors report a case, on a 59-year-old female patient, of angiolymphoid hyperplasia with eosinophilia (AHE) associated to a thrombopenic purpura (TP) of which the evolution is parallel. The clinical aspect is made of sub-cutaneous nodules of various sizes (1 or 2 cm on an average) and of more superficial, erythematous, sometimes telangiectatic, pseudo-angiomatous nodules. There are (about) 25 nodules, located on the face, the neck, the arms and the thorax, sometimes pruriginous: the rest of the examination is negative excepting axillary and inguinal small size lymph nodes and of a dermographism. The anatomopathological examination in optical microscopy, shows a dermo-epidermal lymphocytic infiltrate with which mingle numerous eosinophilic leucocytes. The dermal vessels are very altered, with a swelling endothelium and a proliferation of endothelial and perithelial cells filling up in large part the vascular section. The biological investigation show essentially: a slight and altering hypereosinophilia (between 500 and 800/mm3); a low amount of blood-platelets (between 95,000 and 130,000/mm3); an increase of the seroconversion enzyme of angiotensin (75 UI; N less than 52 UI); are normal or negative: ESR, protein electrophoresis, immunological tests. The diagnosis of AHE is held back and the clinical evolution is done in several stages: under general corticotherapy (prednisone 1 mg/kg/j): progressive decrease of the nodules, but stopping of the therapy by the patient after 4 months; testing of treatment by thalidomide (100 mg/day) interrupted after 2 weeks because of the aggravation of the thrombopenia (25,000/mm3); occurrence of a thrombopenic purpura (TP) (amount of platelets 10,000/mm3) without a serious haemorrhagic syndrome, evolving in a parallel way to the outbreak of AHE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMedDate not supplied

Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging.

The appearance and evolution of brain infarcts over 3 days following proximal occlusion of the left middle cerebral artery (MCA) in SHR rats were measured non-invasively by magnetic resonance imaging (MRI). Infarcts were clearly visible in coronal, T2 weighted brain sections, 24, 48 and 72 h after MCA occlusion in the left hemisphere, as areas of increased NMR signals. The infarcts were quantified by pixel counting in each section, the sum of 4 sections representing an accurate estimate of the total infarct size. The location and extent of infarction, determined by MRI, were found to be highly reproducible and correlated well with post-mortem histological and biochemical data. A neurological score, made every 24 h, paralleled the evolution of the infarct size, which culminated after 48 h. Pre- or post-treatment of MCA occluded rats with the dihydropyridine calcium antagonist PN 200-110 resulted in a substantial reduction of infarct size, determined by MRI 24, 48 and 72 h after infarction, compared to vehicle treated controls. These findings were corroborated by corresponding improvements of the neurological scores as well as histological and biochemical data. Post-treatment with nimodipine showed qualitatively similar effects. These results support the notion that calcium antagonists, through vascular and/or metabolic mechanisms, are effective in treating acute stroke. Since they were obtained in a chronic, relevant model of stroke with a method directly applicable also to humans, they should encourage further clinical studies with calcium antagonists.

Animals↗