bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal Migration and Regional Development: The Khon Kaen Development Centre of Northeast Thailand
Authors: Sternstein Larry
Published: April 2011

When Khon Kaen town was designated the development centre for Northeast Thailand in 1962 it was a small provincial capital, undistinguished save for being the most centrally located on-rail town in the region. (See Figure 1.) Khon Kaen has since been transformed. Several tens of government agencies concerned with development in the Northeast now have regional or sub-regional offices in or near Khon Kaen. A regional technical school and the University of the Northeast have been established. A network of paved roads, a spacious, modern bus terminal and a newly constructed airfield, in addition to a renovated railway, have made Khon Kaen a major transportation hub, readily accessible to northeasterners and indeed to all of Thailand. Khon Kaen was the first provincial centre to have a town plan. Although this plan, designed to make Khon Kaen a showpiece of modern urban development, has not been carried out in toto, urban facilities have been greatly improved and expanded, and commercial activity has diversified and burgeoned. The population of Khon Kaen town increased more than fifty percent in the period 1960–1970.
King-making in Cambodia: From Sisowath to Sihanouk
Authors: Osborne Milton
Published: April 2011

The question of exactly why Prince Norodom Sihanouk was placed on the Cambodian throne in 1941 has long been a matter of interest to observers of Khmer affairs. A range of explanations has been offered, with varying emphases and some contradictions. Following Prince Sihanouk's deposition in March 1970 the question has, once again, been discussed in some detail with the Prince, himself, providing new commentary on the events of 1941.1 Archives recently opened in France which include documents relating to 1941 have much to add to the story of Sihanouk's accession. If they do not answer all the questions that an historian might pose, they certainly provide a much more detailed account than has previously been available. What is more, the newly released archival records carry the history of succession difficulties in Cambodia back through the generation that preceded Sihanouk's own accession giving a fascinating insight into the interaction between the French and the Cambodian royal family. The history that emerges involves intrigue, sustained and unsustained allegations, and revelations of human frailty. Despite the dangers of ethnic stereotypes, the events to be recounted in this article seem very Cambodian and very French.
A Reply to P.T. Bauer's Comment on Post-War Malayan Rubber Policy
Authors: Rudner Martin
Published: April 2011

Professor P. T. Bauer's Comment on Post-War Malayan Rubber Policy re-opens discussion on policy-making and developments in the Malayan rubber industry following the Second World War. However, most of the discussion in Professor Bauer's Comment does not relate to, and in fact explicitly dismisses the specific historical subject of my article to which it purports to refer, “Rubber Strategy for Post-War Malaya, 1945-1948” (Journal of Southeast Asian Studies, Vol. 1, No. 1, (March 1970, pp. 23-36). Yet he raises certain points which call for reply, and some for brief comment.
The Timber Industry and Forest Administration in Sabah under Chartered Company Rule
Authors: John David W.
Published: April 2011

Despite the dominant role the timber industry now plays in the economy of Sabah, little is known of the development of the industry prior to the Pacific War. The small amount that has been published on the pre-war situation appears in the Malayan Forester, but the destruction of records in Sabah during the Japanese Occupation has greatly impeded detailed research. For the present study the papers of the British North Borneo (Chartered) Company now held in London have served as a source of far more comprehensive information than occurs in the oft-quoted secondary sources. The aim of this paper is to provide the first detailed account of forest policy and administration, and a systematic analysis of the development of the timber industry in pre-war North Borneo.
The 1959 Singapore General Election
Authors: Chung Ong Chit
Published: April 2011

The 1959 election marked a turning point in the constitutional and political development of Singapore. It was the culmination of what had happened since the restoration of British government in Singapore after the Second World War. After the war, the British returned to Malaya to re-establish their rule. But Singapore had seen the humiliating defeat of the British in the march of Japanese militarism. The myth of the invincible supremacy of the white colonialists was shattered. The mood and tempo of the times were increasingly different from that of the pre-war period. The call of the day was decolonisation and independence from colonial domination.
Southeast Asian Studies at Kyoto University
Authors: Ichimura Shinichi
Published: April 2011

The Center for Southeast Asian Studies at Kyoto University is a research institute established officially in 1965 after several years of unofficial existence and now has an establishment of twenty-three permanent research staff members and four visiting foreign scholars. It plays a central role in promoting area research on Southeast Asia at Kyoto University. There are also more than one hundred scholars at other faculties and research institutes of Kyoto University who have been engaged in Southeast Asian Studies. As affiliated members of the Center, they can participate in the Center's various research projects. The research results are made available both in Japanese and English in South East Asian Studies (a quarterly journal), Japanese and English monographs, reprint series and discussion papers. Information on these publications is provided in SEAS: The Second Report 1969–1972 (with supplement), a copy of which is available free of charge from the Kyoto Center.
Interdisciplinary Research and Area Studies
Authors: Ichimura Shinichi
Published: April 2011

Although there are many problems in development research that can be adequately analysed along the lines of traditional single disciplinary research, these studies frequently reach the boundaries of each discipline and require some way of combining with the knowledge of neighbouring sciences to further the analysis. This combination of knowledge may be encyclopaedic only in the sense that the various inquiries into the same or related problems by various disciplines are simultaneously attempted and their conclusions are arranged in parallel or cumulative fashion so as to facilitate a synthetical understanding of the different aspects of the development process. Such a type of research may be called multidisciplinary.
An Ecological Interpretation of Thai History
Authors: Takaya Yoshikazu
Published: April 2011

Central Thailand comprises three ecologically distinctive areas, i.e. the mountain area, the floodplain and the delta, as shown in Fig. 1.

These three areas relied on irrigation agriculture making full use of the distributary system of intermountain basins. The mountain area was the main stage for the traditional “Muang” during the period from the 12th to the 14th centuries.
Some Problems of Brunei Chronology
Authors: Nicholl Robert
Published: April 2011

Owing to the absence of dates in historical manuscripts and on monuments, Brunei chronology has been based upon traditional dates of uncertain origin. The object of this article is to take such events in Brunei as can be chronicled in external sources and to compare these foreign dates with those traditionally accepted.
The Role of Governor D.J. Jardine in Improving the Welfare of the Indigenous People of Sabah, 1934–37
Authors: Osman Sabihah
Published: April 2011

Douglas J. Jardine was Governor of British North Borneo (Sabah) from August 1934 to May 1937. Despite his short period in office, Jardine succeeded in bringing about considerable improvement in the country. The most important feature of his administration was his personal interest in the welfare of the native population, particularly with regard to their administration, education and health.
Punitive Colonialism: The Dutch and the Indonesian National Integration
Authors: Nawawi Mohd. A.
Published: April 2011

It is widely acknowledged that colonial experience has greatly affected the political development of ex-colonial countries. In particular, colonialism has often been regarded as the most important, if not the sole, basis of national integration in many of these countries. At the same time, the literature on political development still lacks a critical evaluation of the impact of colonial rule on these ex-colonies. The following essay is an initial assessment of the contribution of Dutch colonialism to the national political integration of Indonesia. Such an evaluation has not been explicitly made, even though the literature on Indonesia does not lack sweeping judgments by both Indonesian nationalists and the apologists for the Dutch “mission interrupted”.
The Selangor Succession Dispute, 1933–38
Authors: Wah Yeo Kim
Published: April 2011

Under the various treaties and quasi-treaties between Britain and the Malay States, matters affecting ‘Malay custom and religion’ were under the jurisdiction of the Rulers and their chiefs. The succession to a Malay throne was a matter of Malay custom but, since the establishment of British rule, it came to be controlled and regulated by the colonial power. At times this control had been exercised in a manner distasteful to the Malay ruling houses, but no Malay Ruler had come out in open opposition to a British choice of a successor to his throne until the Selangor Succession Dispute. To the great surprise of the colonial government, the old Sultan openly resisted its attempt to impose on Selangor a Raja Muda (Heir Apparent) who was unacceptable to him and to a section of his family. This paper proposes to discuss the Selangor Succession Dispute which raged for five years in Malaya and London with important repercussions on British policy towards the Malay States.
The Origins of the Limbang Claim
Authors: Crisswell C. N.
Published: April 2011

Tun Abdul Razak, the prime minister of Malaysia, has recently announced that his Government cannot consider the claim to the Limbang River made by the Sultan of Brunei. This dispute has its origins in the 1880's when North Borneo and Sarawak were intriguing against each other to gain possession of the remains of the once powerful Sultanate. Since that time the problem of the Limbang has smouldered continually, every now and then breaking into a fitful glow. The problem is a complex one and has not hitherto received detailed scholarly analysis.
The Bonds of Culture and Commonwealth in Southeast Asia
Authors: Boyce P. J.
Published: April 2011

To what extent can it still be argued that Australia enjoys a ‘special relationship’ with Malaysia and Singapore, and, if such a relationship exists, is its maintenance conditional upon purely strategic advantage? ‘Special relationship’ are elusive concepts in the vocabulary of international diplomacy. Presumably they require both objective and subjective proof of their existence. In other words, it would take more than an affirmation by the Malaysian and Australian governments to show that a special relationship existed between them. Demonstrations of unusual solidarity or harmony of interest would presumably be sought to test the affirmations.
A Re-Investigation of the Gwe of Eighteenth Century Burma
Authors: Brailey Nigel J.
Published: April 2011

An insuperable difficulty presents itself in tracing with any degree of correctness the origins of a barbarous race of people who possess no written character, and whose history is clothed in the obscurity of legendary traditions handed down to successive generations by oral Agency alone, in which much of the fabulous becomes mixed with certain transactions of a nature to state indefinitely the ‘era’ of their occurrence, but affording no positive source from whence to derive anything approaching a correct ‘data’. It is then thus with the race of the ‘Kaya’, so called by themselves in their own language, that of ‘Karen Nee’ or ‘Red Karens’ being given to them by the Burmese and surrounding people, from the predominating color of their costume — the short drawers and turban being generally of that color, which distinguishes them from other tribes of ‘Karens’ whose attire consists of a white tunic and are on that account termed ‘Karen Pyee’ or ‘White Karens’.
Ageing activists: who gets involved in older people's forums?
Authors: BARNES MARIAN , HARRISON ELIZABETH , MURRAY LESLEY
Published: April 2011

Based on research with members of two Senior Citizens Forums in the South East of England, this article examines the biographies and motivations of those who get involved in such activities, with particular emphasis on (a) how they see themselves in relation to ‘other older people’ and (b) their relationships with the places in which they live. We address these issues in relation to the characterisation of participants in such forums as the ‘usual suspects’ whose legitimacy to speak on behalf of others may be questioned, and by reference to a growing recognition of the significance of place in the lives of older people. Whilst the locations of the two Forums studied are geographically close, culturally they are quite distinct and we identify important differences in motivations, backgrounds and priorities of forum members in the two places that are associated with these differences. Our research confirms that place-based participation tends to engage those who are fitter and who have more social and cultural capital, but questions assumptions that this means they are spaces for the pursuit of self-interest.
Pea and bean germination and seedling responses to temperature and water potential
Authors: Raveneau M.P. , Coste F. , Moreau-Valancogne P. , Lejeune-Hénaut I. , Durr C.
Published: April 2011

Legumes are crops that develop in cropping systems with relatively low inputs and are suitable to a more sustainable agriculture. Successful crop establishment, which is crucial for reliable plant production, depends on seed quality, environmental factors and genotypes. We studied pea and bean germination and seedling growth at various temperatures (5–40°C) and water potentials ( − 0.2 to − 1.5 MPa) using winter and spring pea and two common bean seeds produced in different conditions. The germination base temperature was − 1.1°C for pea seeds, and seeds of the winter genotype germinated more rapidly than those of the spring genotype. The base temperature for bean seed germination was 5.1–9.6°C, depending on the seed lot. The germination base water potential was about − 2 MPa for both species. The base temperatures for shoot elongation were higher (3–6°C) than those for germination. A review of the literature on other legumes confirmed that the differences in the responses of the legume seeds and seedlings to different temperatures were associated with their geographic origin. These results help understanding of pea and bean crop establishment, provide crop model parameter values and contribute to the search for genetic variability.
The reduction of seed-specific dehydrins reduces seed longevity in Arabidopsis thaliana
Authors: Hundertmark Michaela , Buitink Julia , Leprince Olivier , Hincha Dirk K.
Published: April 2011

Dehydrins are late embryogenesis abundant (LEA) proteins that accumulate during seed maturation and in response to abiotic stresses in vegetative tissues. They are thought to protect cellular components from dehydration stress. However, whether they play a role in survival in the dry state is not clear. In this study, an RNA interference (RNAi)-construct against the seed-expressed dehydrin of Arabidopsis thaliana, LEA14 (At2g21490), was introduced to wild-type plants, which led to a strong reduction in transcript abundance of the target gene as well as that of two other seed-expressed dehydrin homologues, XERO1 (At3g50980) and RAB18 (responsive to abscisic acid 18, At5g66400) in the transformants. Mature, dry seeds from the RNAi plants germinated to at least 95% after rehydration, indicating that seed desiccation tolerance was not affected, while they exhibited a twofold reduction in longevity. When stored at 75% relative humidity and 35°C, the seeds of two independent RNAi lines lost 50% of their viability in 10 d and 5 d, respectively, while it took 17 d for wild-type seeds to lose 50% viability. In addition, when seeds were imbibed in the presence of 100 mM NaCl, the seeds of RNAi plants exhibited reduced germination compared to wild-type seeds, suggesting that at least one of the three seed-specific dehydrins plays a role both against deterioration during storage at low moisture content and when imbibed tissues are submitted to salt stress at high moisture.
Geopolitics and Domestic Politics: Greece's Policy Towards the Great Powers During the Unravelling of the Inter-War Order, 1934–1936
Authors: RIZAS SOTIRIS
Published: April 2011

This article examines the evolution of Greece's foreign policy from a position of relative detachment to an increasing involvement in international affairs that eventually led to the country's realignment with Britain during the Abyssinian crisis. It is argued that Greece's foreign policy shift was a result of an interplay between a perceived threat of Italian revisionism, Britain's reappearance in the Eastern Mediterranean during the Abyssinian crisis and domestic political dynamics that led to the defeat of Eleftherios Venizelos who favoured a foreign policy detached from combinations of great powers.
Editor's Introduction
Authors: Panagopoulos Costas
Published: April 2011

Congressional midterm elections were held in the United States in November 2010. Midterm cycles have historically been unkind to the party of the incumbent president, which has on average lost 24 seats in the U.S. House and 4 seats in the U.S. Senate in midterms during the postwar era. In the 2010 general elections, Democrats, who had enjoyed unified control of the federal government since January 2009, suffered devastating defeats in congressional, gubernatorial, and state legislative races nationwide. Democrats lost a total of 63 seats in the U.S House of Representatives—a loss greater than in any other midterm in the postwar period—relinquishing control to the GOP for the first time since 2007 and ushering in a new era of divided government in Washington. Republicans also made gains in the U.S. Senate, although Democrats ultimately retained control of the chamber by a narrow margin of 51 to 47 (two independents also caucus with the Democrats).
The Salience of the Democratic Congress and the 2010 Elections
Authors: Jones David R. , McDermott Monika L.
Published: April 2011

The results of the 2010 congressional elections were indeed historic. The loss of 63 seats by the Democrats was the biggest electoral loss by any party since 1948, making the more recent 1994 and 2006 turnovers pale by comparison. The question that political scientists naturally ask after an event of this magnitude is—why? This article addresses this question by analyzing the role played by the public's attitudes toward Congress.
Tea Time in America? The Impact of the Tea Party Movement on the 2010 Midterm Elections
Authors: Karpowitz Christopher F. , Monson J. Quin , Patterson Kelly D. , Pope Jeremy C.
Published: April 2011

By winning the presidency and strengthening its majority in both chambers of Congress, the 2008 election gave control of the government to the Democratic Party. However, as the 2010 election season unfolded, the news for the Democratic Party could not have been much worse. Economic conditions had not improved dramatically. A bitter and lengthy fight over health care reform signaled to citizens that little had changed in how Washington, DC, governed. The stimulus package and its impact on the federal debt caused unease in a segment of the electorate that was concerned with the size of government. In this context, observers of American politics began to take note of the number of citizens affiliating with, or at least expressing favorability toward, a loose coalition of groups known as the Tea Party movement. Tea Party rallies began to occur throughout the United States, seeking to draw attention to the movement's primary issues.
What Happens at the Journal Office Stays at the Journal Office: Assessing Journal Transparency and Record-Keeping Practices
Authors: Yoder Stephen , Bramlett Brittany H.
Published: April 2011

Dissemination of journal submission data is critical for identifying editorial bias, creating an informed scholarly marketplace, and critically mapping the contours of a discipline's scholarship. However, our survey and case study investigations indicate that nearly a decade after the Perestroika movement began, political science journals remain reserved in collecting and releasing submission data. We offer several explanations for this lack of transparency and suggest ways that the profession might address this shortcoming.
Prioritizing Active Learning: An Exploration of Gateway Courses in Political Science
Authors: Archer Candace C. , Miller Melissa K.
Published: April 2011

Prior research in political science and other disciplines demonstrates the pedagogical and practical benefits of active learning. Less is known, however, about the extent to which active learning is used in political science classrooms. This study assesses the prioritization of active learning in “gateway” political science courses, paying specific attention to simulations, structured debates, and the case method. Nearly five hundred individual course syllabi for introductory-level political science courses are examined. Although the level of active learning prioritization is surprisingly low, the dimensions on which it varies suggest opportunities for adoption across subfields and classes of varying size.
Late-Life Social Activity and Cognitive Decline in Old Age
Authors: James Bryan D. , Wilson Robert S. , Barnes Lisa L. , Bennett David A.
Published: April 2011

We examined the association of social activity with cognitive decline in 1138 persons without dementia at baseline with a mean age of 79.6 (SD = 7.5) who were followed for up to 12 years (mean = 5.2; SD = 2.8). Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7). A one point increase in social activity score (range = 1–4.2; mean = 2.6; SD = 0.6) was associated with a 47% decrease in the rate of decline in global cognitive function (p < .001). The rate of global cognitive decline was reduced by an average of 70% in persons who were frequently socially active (score = 3.33, 90th percentile) compared to persons who were infrequently socially active (score = 1.83, 10th percentile). This association was similar across five domains of cognitive function. Sensitivity analyses revealed that individuals with the lowest levels of cognition or with mild cognitive impairment at baseline did not drive this relationship. These results confirm that more socially active older adults experience less cognitive decline in old age. (JINS, 2011, 17, 998–1005)
Structural analysis of 5′‐mRNA–cap interactions with the human AGO2 MID domain
Authors: Frank Filipp , Fabian Marc R , Stepinski Janusz , Jemielity Jacek , Darzynkiewicz Edward , Sonenberg Nahum , Nagar Bhushan
Published: April 2011

In RNA silencing, microRNA (miRNA)‐mediated translational repression occurs through mechanisms that do not invoke messenger‐RNA (mRNA) target cleavage by Argonaute proteins. The nature of these mechanisms is unclear, but several recent studies have proposed that a direct interaction between the mRNA–cap and the middle (MID) domain of Argonautes is involved. Here, we present crystallographic and NMR data demonstrating that cap analogues do not bind significantly to the isolated MID domain of human Argonaute 2 (hAGO2) and are found in the miRNA 5′‐nucleotide binding site in an implausible binding mode. Additionally, in vitro pull‐down experiments with full‐length hAGO2 indicate that the interaction with cap analogues is nonspecific.
Training biology's new romantics
Authors: Tomaska Lubomir
Published: April 2011

The scientific knowledge amassed over the last 50 years is too much for one brain. Education should focus on training biologists to analyse and think, rather than just remember facts.
Osterix finds its master
Authors: Kousteni Stavroula
Published: April 2011

A paper in this issue of EMBO reports by Tohmonda et al demonstrates that the IRE1–XBP1 branch of the unfolded protein response is activated during BMP2‐induced osteoblast differentiation, and identifies the osteoblast‐specific transcription factor Osterix as a direct target of XBP1.
An Intravenous Technique for the Measurement of Cerebral Vascular Extraction Fraction in the Rat
Authors: Clark H. Brent , Hartman Boyd K. , Raichle Marcus E. , Preskorn Sheldon H. , Larson Kenneth B.
Published: April 2011

An intravenous injection method to measure cerebral vascular extraction fractions of highly diffusible substances in the rat is described. The brain extraction fractions of 3H-labeled water ( Ew) and ethanol ( Ee) were defined as the ratio of either of those tracers to the freely diffusible reference tracer, 14C-butanol, in the brain, divided by the ratio of the tracers available for the extraction during the time between simultaneous intravenous injection of the tracers and decapitation of the rat. Ew and Ee were measured in five regions of brain, including brainstem and cerebellum, under Paco2 conditions ranging from 15 to 85 mm Hg. The extraction fractions for both test tracers were shown to vary with Paco2-induced flow changes according to the equation, ln(1 – E) = − PS/ F. When PS/ F values calculated from regional measurements of Ew and Ee were plotted versus Paco2, least squares regression equations of the plots could be used to compare permeabilities of both tracers at any given Paco2 value. Ratios of the permeabilities of water and ethanol varied regionally but were relatively constant in a given region under different flow states. This intravenous injection method allows for accurate measurement of the extraction fractions of even highly diffusible tracers under varied flow conditions in all brain regions regardless of arterial blood supply.
Use of 2-Deoxy-D[1-11C]Glucose for the Determination of Local Cerebral Glucose Metabolism in Humans: Variation within and between Subjects
Authors: Reivich M. , Alavi A. , Wolf A. , Greenberg J. H. , Fowler J. , Christman D. , MacGregor R. , Jones S. C. , London J. , Shiue C. , Yonekura Y.
Published: April 2011

The deoxyglucose technique for the measurement of local cerebral glucose metabolism (LCMRgl) has been widely applied in animals utilizing 14C-deoxyglucose and in humans employing 18F-fluorodeoxyglucose. Repeat studies in humans over a relatively brief period of time have not been possible because of the 110-min half-life of fluorine-18. With the synthesis of 11C-deoxyglucose it has now become possible to utilize this short-lived (20 min) tracer for the measurement of LCMRgl and to determine its variability within subjects over a 2-h period. The kinetic rate constants for 11C-deoxyglucose were determined for gray and white matter and found to be very similar to those for 18F-fluorodeoxyglucose, suggesting that these two analogues of glucose have similar affinities for the facilitated transport system and are similar substrates for hexokinase in the brain. The coefficient of variation of repeated measurements of LCMRgl in a series of six normal subjects was 5.5% to 8.7% for various gray matter structures and 9.7% to 14.0% for white matter structures. The pattern of cerebral metabolic rates is relatively constant in a given individual when the conditions of the study are unchanged. The ability to make repeat measurements in the same subject reduces the variance due to between-subject differences, allowing smaller changes in LCMRgl to be detected with confidence.
Effects of Immobilization Stress on Cerebral Blood Flow and Cerebrovascular Permeability in Spontaneously Hypertensive Rats
Authors: Ohata M. , Takei H. , Fredericks W. R. , Rapoport S. I.
Published: April 2011

Immobilization of unanesthetized, freely breathing, 10–12-month-old, spontaneously hypertensive rats (SHR) did not significantly alter regional cerebral blood flow (rCBF) in 13 of 14 brain regions assayed. After 5 or 15 min of immobilization, rCBF was unchanged except at the frontal lobe, where it rose significantly by 21%. Furthermore, immobilization did not increase the cerebrovascular permeability–area product for 14C-sucrose, except at three brain regions. The results indicate that immobilization of SHR does not significantly affect rCBF or blood–brain barrier permeability in most regions of the brain, and suggest that adequate autoregulation of rCBF is maintained under stress.
Global Cerebral Vasodilatation Elicited by Focal Electrical Stimulation within the Dorsal Medullary Reticular Formation in Anesthetized Rat
Authors: Iadecola Costantino , Nakai Masatsugu , Arbit Ehud , Reis Donald J.
Published: April 2011

We examined the effects of electrical stimulation of a restricted area of the dorsal medullary reticular formation (DMRF) on regional cerebral blood flow (CBF) in anesthetized (by chloralose), paralyzed (by curare) rats. CBF was measured in tissue samples by the Kety principle, with 14C-iodoantipyrine as indicator. Stimulation of DMRF elicited a widespread, significant increase in CBF in 12 of 13 areas. The increase in flow was greatest in cerebral cortex, up to 240% of control. However, it was also substantially increased in selected regions of telencephalon, diencephalon, mesencephalon, and lower brainstem, but not cerebellum. In contrast, electrical stimulation of the midline (interstitial nucleus of the medial longitudinal fasciculus) 1 mm medial to the DMRF did not change CBF. The increase in CBF evoked by DMRF stimulation persisted after transection of the spinal cord at C1 or cervical sympathetic trunk. We conclude that excitation of neurons originating in or passing through the DMRF can elicit a potent and virtually global increase of CBF. The effect appears to be mediated by intrinsic pathways of the central nervous system.
Increased Blood—Brain Barrier Transport of Protein-Bound Anticonvulsant Drugs in the Newborn
Authors: Cornford Eain M. , Pardridge William M. , Braun Leon D. , Oldendorf William H.
Published: April 2011

The extraction of heroin, caffeine, diphenylhydantoin, and phenobarbital has been measured in the newborn, suckling, and adult brain. Anticonvulsant drugs such as diphenylhydantoin and phenobarbital are bound by plasma protein, and it is generally believed that only the fraction of drug that is free (dialyzable) in vitro is available for transport through the blood-brain barrier in vivo. In both the adult and neonatal rat or rabbit, lipid-mediated transport of free phenytoin occurs. In addition, a fraction of the drug that enters the capillary bound to plasma protein also gains access to the brain. A greater amount of protein-bound drug permeates the newborn brain, and this is ascribed to a longer capillary transit time in the neonate. With regard to phenobarbital, the total (i.e., both free and protein-bound) plasma drug enters the newborn brain. In contrast, no protein-bound phenobarbital permeates the adult brain, and it is only the free drug fraction that gains access to the brain. Since the blood—brain barrier permeability—surface area product for the two anticonvulsants is unchanged in newborn and older animals, the age-related differences in brain uptake of protein-bound drugs can be attributed to developmental changes in cerebral blood flow and capillary transit time. The increased transport of protein-bound drugs in the newborn may cause increased concentrations (i.e., brain:plasma ratios) of these anticonvulsants in the neonatal brain.
Regional Assessment of Energy-Producing Metabolism following Prolonged Complete Ischemia of Cat Brain
Authors: Paschen W. , Hossmann K.-A. , van den Kerckhoff W.
Published: April 2011

The regional content of biochemical substrates of energy-producing metabolism was assessed in cat brains following prolonged cerebral ischemia. Ischemia was produced by intrathoracic occlusion of the innominate, the left subclavian, and both mammarian arteries, and additional lowering of the systolic blood pressure to 80 mm Hg. After 60 min of global ischemia and 3 h of recirculation, the regional distribution of glucose, ATP, and NADH was evaluated on intact brain sections by bioluminescence and fluorescence techniques. Additionally, the content of different substrates related to energy and redox state was assessed in small tissue samples. Recirculation following global ischemia led to three different patterns of biochemical substrates: in 6 of 14 animals, regional distribution of glucose, ATP, and NADH was similar to that of control animals. These animals exhibited recovery of evoked potentials and reappearance of low-voltage EEG activity. In five animals, ATP was decreased in small circumscribed regions belonging to border zones of cerebral vessels. In these regions, glucose was high and NADH-fluorescence was low, indicating that glucose deficiency was not the limiting factor for ATP depletion. In this group, evoked potentials recovered, but the EEG did not. In three animals, glucose and ATP were low throughout the whole brain, and electrophysiological recovery was absent. The pattern and localization of biochemical lesions and the correlation with hemodynamic and electrophysiological parameters suggest that disturbances of energy-producing metabolism are caused by regional ischemic episodes during the recirculation period and can be prevented by the immediate and homogeneous blood reperfusion of the brain after cerebrocirculatory arrest.
Role of Prostaglandins in the Response of the Cerebral Circulation to Carbon Dioxide in Conscious Rabbits
Authors: Busija David W.
Published: April 2011

The role of prostaglandins in maintenance of resting cerebral blood flow (CBF) and in cerebral vasodilatation during hypercapnia remains controversial. The effect of indomethacin, a cyclo-oxygenase inhibitor, on CBF and cerebrovascular resistance (CVR) was examined in conscious animals. Regional and total CBF were measured with radioactive microspheres, and the efficacy of blockade of prostaglandin synthesis by indomethacin was examined by the cranial window method. CBF was measured in conscious rabbits with 15-μm radioactive microspheres during normocapnia (Pco2 ≈ 30 mm Hg) and hypercapnia (Pco2 ≈ 60 mm Hg), before and after intravenous administration of indomethacin (10 mg/kg) or vehicle (n = 6 for each). Thus, each animal served as its own control. CBF was 84 ± 6 and 190 ± 27 (mean ± SE) ml/min/100 g during normocapnia and hypercapnia, respectively, before indomethacin, and 78 ± 5 ml/min/100 g during normocapnia and 180 ± 16 ml/min/100 g during hypercapnia following indomethacin. Thus, indomethacin did not change normocapnic CBF. In addition, cerebrovascular responses during hypercapnia did not vary between the indomethacin and vehicle groups. Indomethacin did not attenuate increases in blood flow in any area of the brain, except slightly to cerebellum during hypercapnia. Indomethacin did not affect CVR during normocapnia or hypercapnia. The topical application of arachidonic acid (75 and 150 μg/mg), dissolved in cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin (10 mg/kg) blocked vasodilatation produced by arachidonic acid by 87% (p < 0.05). Thus, indomethacin, at a dose that effectively inhibits prostaglandin synthesis, did not change resting CBF or CVR or attenuate the increase in CBF or decrease in CVR during hypercapnia. These findings suggest that prostaglandins do not contribute significantly to regulation of the cerebral circulation during normocapnia and hypercapnia.
Effect of Tissue Heterogeneity on the Measurement of Cerebral Blood Flow with the Equilibrium C15O2 Inhalation Technique
Authors: Herscovitch Peter , Raichle Marcus E.
Published: April 2011

The equilibrium C15O2 inhalation method for measuring cerebral blood flow with positron emission tomography (PET) is based on a one-compartment model for which it is assumed that the local flow and partition coefficient are uniform in the tissue region in which flow is to be determined. However, because of the limited spatial resolution of PET, a region of interest will contain a mixture of gray and white matter. We used a computer simulation to examine the effect of this heterogeneity on flow measurement in both normal and pathological states. With gray and white matter flows of 0.80 and 0.20 ml/min/g, respectively, flow is underestimated by a maximum of 20% in a region that is 30% gray. Errors occur not only because of flow heterogeneity, but also because of heterogeneity of partition coefficient and the sensitivity of the method to errors in partition coefficient. Larger errors occur in the case of cerebral hyperemia, although the method becomes more accurate with ischemia. In the case of simulated brain tumor, the accuracy of flow determination varies considerably, depending on the flow and partition coefficient of the tumor and of the surrounding tissue. Finally, incremental changes in gray matter flow, as would occur with functional cortical activation, are not well reflected. Thus, the equilibrium C15O2 inhalation method is limited in its ability to accurately quantitate local cerebral blood flow in heterogeneous tissue regions.
Brain pH in Focal Cerebral Ischemia and the Protective Effects of Barbiturate Anesthesia
Authors: Anderson Robert E. , Sundt Thoralf M.
Published: April 2011

Intracellular brain pH was measured with a lipid-soluble, pH-sensitive fluorescent indicator in 16 squirrel monkeys. Eight of these were under halothane anesthesia and eight under barbiturate anesthesia. Measurements were taken before, during, and after focal incomplete ischemia. Brain pH following 3 h of cerebral focal ischemia changed from a normal value of 7.0 to 6.5 and 6.2 in animals studied under barbiturate and halothane anesthesia, respectively. Brain pH returned toward normal after flow was restored in animals under barbiturate anesthesia but continued to deteriorate in animals under halothane anesthesia.
Cerebrovascular Response to Acute Decreases in Arterial PO2
Authors: Wagerle L. Craig , Orr James A. , Shirer Hampton W. , Kiorpes Anthony L. , Fraser David B. , DeSoignie Roland C.
Published: April 2011

The purpose of these studies was to examine the time course of the cerebrovascular response to acute hypoxia in unanesthetized ponies. An electromagnetic flow transducer chronically placed on the internal carotid artery of the pony allowed continuous recording of internal carotid artery blood flow (ICBF) which has been shown to be representative of cerebral blood flow (CBF). The ponies were subjected to three levels of acute isocapnic hypoxia (PaO2 = 62, 44, and 39 mm Hg for hypoxia level I, II, and III, respectively), and the temporal and steady-state cerebrovascular response was examined. ICBF increased significantly at all three hypoxia levels (8, 25, and 40% at hypoxia I, II, and III, respectively). This increase was rapid in the two most severe levels of hypoxia, beginning within 45 s, and was complete within 90 s. The increase lagged behind the reduction in PaO2 by 24–28 s. During the very mild level of hypoxia (I), no such rapid increase in flow was observed; rather, the increase occurred only after 5 min of hypoxia. Microsphere (15 μm diameter) measurements from six ponies during the most severe level of hypoxia (III) demonstrated that CBF increased 38%. Noncerebral tissues known to be vascularly connected to the circle of Willis, and thus capable of receiving blood flow via the internal carotid artery, either did not change or increased so slightly during hypoxia that their effect on ICBF was minimal. These data imply that mediators of the cerebrovascular response to hypoxia must be capable of sensing hypoxia and affecting cerebrovascular smooth muscle within seconds. The slower time course in mild hypoxia suggests other mechanisms may be involved when PaO2 is greater than 50 mm Hg.
Adenosine Causes Dilatation and Constriction of Hypothalamic Blood Vessels
Authors: Livemore P. , Mitchell G.
Published: April 2011

The effect of adenosine on intraparenchymal cerebral blood flow was examined in conscious rabbits with the 133Xe clearance technique. Perivascular application of 10−3 and 10−4 M adenosine to hypothalamic blood vessels increased hypothalamic blood flow by ∼50% (p < 0.005). This vasodilatation was attenuated by the intrahypothalamic injection of the β-adrenergic receptor antagonist propranolol, but was unaffected by α-adrenoreceptor blockade with phenoxybenzamine, or depression of neuronal activity with barbiturate. 2-Chloroadenosine, a stable analogue of adenosine, also increased hypothalamic blood flow by 50% (p < 0.005), but this dilatation was unaffected by propranolol. These results suggest that adenosine increased hypothalamic blood flow at high concentrations by vascular receptor systems dependent on adenosine receptors and adrenergic receptors. Adenosine (10−6 M) reduced hypothalamic blood flow by ∼25% (p < 0.005). This vasoconstriction was unaffected by adrenergic blockade with propranolol or phenoxybenzamine, or by inhibition of neuronal activity with barbiturate. The results suggest that adenosine decreases hypothalamic blood flow at low concentrations by stimulation of adenosine receptors associated with vascular smooth muscle.
Blood Flow Velocity in the Pial Arteries of Cats, with Particular Reference to the Vessel Diameter
Authors: Kobari Masahiro , Gotoh Fumio , Fukuuchi Yasuo , Tanaka Kortaro , Suzuki Norihiro , Uematsu Daisuke
Published: April 2011

The blood flow velocity and diameter of feline pial arteries, ranging in diameter from 20 to 200 μm, were measured simultaneously using a newly developed video camera method under steady-state conditions for all other parameters. There was a linear relationship between blood flow velocity and pial artery diameter ( y = 0.340 x + 0.309), the correlation coefficient being 0.785 (p < 0.001). The average values for blood flow velocity in pial arteries <50 μm, ≧50 but <100 μm, ≧100 but <150 μm, and ≧150 μm in diameter were 12.9 ± 1.3, 24.6 ± 3.4, 42.1 ± 4.7, and 59.9 ± 5.3 mm/s, respectively. Blood flow rate was calculated as a product of the cross-sectional area and the flow velocity. The blood flow rate increased exponentially as the pial artery diameter increased ( y = 2.71 × 10−4 x2.98). The average values for blood flow rate in pial arteries <50 μm, ≧50 but <100 μm, ≧100 but <150 μm, and ≧150 μm in diameter were 12.8 ± 1.5, 122.1 ± 24.8, 510.2 ± 74.8, and 1524.2 ± 174.4 10−3 mm3/s, respectively. Hemorheological parameters such as the wall shear rate and Reynolds' number were also calculated. The data obtained provide a useful basis for further investigations in the field of cerebral circulation.
Cerebral Extracellular Calcium Activity in Severe Hypoglycemia: Relation to Extracellular Potassium and Energy State
Authors: Harris Robert J. , Wieloch Tadeusz , Symon Lindsay , Siesjö Bo K.
Published: April 2011

The changes in extracellular Ca2+ (Cae) and K+ (Ke) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N2O anaesthesia), there was an increase in Ke which, at ∼13 m M, was associated with a fall in Cae. Ke peaked at 48 ± 12 m M, and Cae at 0.18 ± 0.28 m M. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Cae recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity, but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.
Effect of the Calcium Antagonist Nimodipine on Local Cerebral Blood Flow: Relationship to Arterial Blood Pressure
Authors: Mohamed A. A. , McCulloch J. , Mendelow A. D. , Teasdale G. M. , Harper A. M.
Published: April 2011

The effect of the calcium antagonist nimodipine on local CBF in 31 regions of the CNS was studied with the [14C]iodoantipyrine autoradiographic technique in lightly anaesthetised, mechanically ventilated rats. Continuous intravenous infusion of nimodipine (1, 2, or 4 μg kg−1 min−1) produced a dose-dependent reduction in MABP (reduced by 26 ± 2% after 30 min of nimodipine, 4 μg kg−1 min−1) and a significant elevation in plasma glucose concentration (increased by 44 ± 2% after 30 min of nimodipine, 4 μg kg−1 min−1). Local CBF was increased significantly during infusions of nimodipine (1 μg kg−1 min−1) in 9 of the 31 regions examined (including the cerebral cortex, hippocampus, hypothalamus, and most thalamic nuclei). In contrast to the increases in CBF observed in forebrain regions, no significant increases in CBF were observed during nimodipine infusions in regions of the lower brainstem, cerebellum, and pons or in myelinated fibre tracts. The proportionately greatest increases in local CBF were observed during infusions of the lowest dosage of nimodipine (1 μg kg−1 min−1), suggesting either that this dosage provokes maximum cerebrovascular relaxation or that effects of increasing concentrations are counteracted by the concomitant systemic hypotension.