MINIREVIEW SERIES FOR THE 50TH
VOLUMEA brief review of Dr F Gotoh's contribution to neuroscience:research in the ®eld of cerebral blood ¯ow and stroke
Takahiro Amano
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan(Received for publication on April 9, 2001)

Abstract. Professor Emeritus Fumio Gotoh began and continues his remarkable career in medicine at
Keio University. Since his graduation from medical school there in 1951, Dr. Gotoh has devoted himself to neurology, especially in the enigmatic ®eld of stroke science. He is most renown for his
groundbreaking research and leadership in the study of cerebral blood ¯ow and metabolism. Beginningwith his doctoral thesis paper in 1959 entitled ``Effects of blood pressure on cerebral circulation,'' ourarticle brie¯y delineates how Prof. Gotoh has paved the path for current and future discoveries inmodern medicine. Although wholly dif®cult to sum up Dr. Gotoh's extensive career in such a shortarticle, we have attempted to chronologically list and furthermore to describe his numerous works.
Herein we describe his expansion to the international arena with his contributions at Wayne State
University as well as his novel cerebral blood gas monitoring techniques now used in modi®ed fashion
throughout the world. From his CO2 -based investigations in animals to his study of the autonomic
nervous system's role in human cerebrovascular control, we remark on Dr. Gotoh's accomplishments
without the use of functional imaging. Yet despite the basic science theme of his research, he has always kept them clinically correlated to entities such as Cheyne-Stokes phenomenon and Shy-Drager
syndrome. Prof. Gotoh has been asked to head some of the most in¯uential stroke societies and was
the second president of the International Stroke Society. In conjunction with leading authorities, hedeveloped a quanti®able, evidence-based stroke scale which was introduced in the International Journal of Stroke in 2001. Today despite his retirement, Dr. Gotoh continues his work in cerebral blood¯ow and metabolism. (Keio J Med 50 (2): 72±80, June 2001)
Key words: Cerebral blood ¯ow, CO2 reactivity, Autonomic nervous system, Nitric Oxide, Stroke scale

it was published in both a Japanese and an English
journal.
That same year, Dr. Gotoh left to study abroad atWayne State University in Michigan, USA. There hejoined the chairman of the department of neurology,
Dr. J.S. Meyer, to study cerebral circulation and metabolism. Dr. Gotoh was proli®c in both research andpublications, elevating him to an associate professorship at that prestigious institution.
By 1969, he had returned home to Keio University as
an assistant professor of internal medicine and continued his work centered in neurology with special
emphasis on cerebral blood ¯ow autoregulation especially due to arterial CO2 ¯uctuations. Soon thereafter,
he developed a device to continuously record humanblood gasses at his laboratory. In 1970, Dr. Fumio
Gotoh initiated a new era at Keio University by estab-

Professor Emeritus Fumio Gotoh of Keio University
was born on March 9, 1926 in Tokyo, Japan. He began
his medical education at Keio University where hegraduated in March of 1951. After a brief internship at
the First National Hospital in Tokyo, he started his
esteemed career in academia in the department of internal medicine at Keio University Hospital. There he
had the opportunity to train under Professor K. Ohmori
and Professor T. Aizawa.
Dr. Gotoh's devotion to the art of medicine was
exempli®ed by his attention to both his patients as wellas his students. Word of his expertise spread rapidly,
especially in the budding ®eld of stroke research.
In 1959, Keio University honored him with a degree
in medical science partly as a result of his groundbreaking article1 entitled ``Effects of blood pressure on
cerebral circulation.'' So in¯uential was this article that72

Keio J Med 2001; 50 (2): 72±80

lishing the Department of Neurology and becoming its®rst Chair.
He quickly advanced to become an associate professor in 1971 and gained the title of ``Professor of Neurology'' in 1972. Because of his stature amongst theworld's leading experts, he was asked to serve as chairperson of the International Meeting of Cerebral Flowand Metabolism held in Tokyo in 1979. Following multiple contributions to the ®eld, Dr. Gotoh was namedProfessor Emeritus in 1991 and became the third president of the Japanese Stroke Society as well as thesecond president of the Japanese Society of Cerebral
Blood Flow, serving from 1991 to 1998. Despite hisnumerous responsibilities, Professor Gotoh tirelessly
leads the International Stroke Society as its second
president from 1996 to 2000.
Despite his retirement, he continues his lifelong
dedication to neuroscience. He is an inspiration andleader to those of us in medicine and certainly a hero tothose of us in the pursuit of neurological studies. It is
hard to truly convey in words how instrumental Dr.
Gotoh has been. It is better to allow his over 220 published works speak for themselves. His primary articles
are listed in the reference.1±163
Professor Gotoh's research career can best be divided
into four periods.
1959±1969: Cerebral Blood Flow Studies atWayne State University
Dr. Gotoh began his studies by inventing a novel
method of continuously monitoring the oxygen & carbon dioxide tension within the cerebral vasculature.4,5With this instrument, he demonstrated that hypocapnic
arterial constriction resulted in decreased ¯ow andanoxic ischaemia using concurrent measurements ofcortical blood ¯ow, pO2 , pCO2 , pH, as well as EEG.2±6
Although at the time carbon dioxide was generally
thought to have the most potent action on cerebral
vasculature, no mechanism of action was immediately
apparent.164,165 These dif®culties related to the inability to differentiate carbon dioxide's effects from associated changes of bicarbonate concentration. It wasProf. Gotoh who theorized that carbon dioxide must act
directly on the arteriolar smooth muscle. He showedthat a large dose of acetazolamide was able to inhibit
the vasomotor action of carbon dioxide.3,12
The next phase of his research involved comparing
gaseous transport rates across brain tissue. Speci®cally,
he compared oxygen and inert nitrogen in living anddead cat brains. The speed at which living brains transmitted these gases was more rapid than dead tissue andblood capillaries were believed to be responsible for thedifference.
Later, carbon dioxide was applied directly and ex-

73

Fig. 1 Cerebral vasodilator action of CO2 (PCO2 electrodetheory).163

ternally to the cerebral cortex resulting in vasodilation,
which could be prevented by preemptive administration
by IV acetazolamide.3,12 This strongly suggested thevasodilatory action of extravascular carbon dioxide, aproduct of cerebral metabolism. Carbonic anhydrase
enhances the reaction CO2  H2  H  HCO3 .12 As
Dr. Gotoh had already demonstrated the neutralizing
effect of acetazolamide on HCO3 , another chemical
mediator was required to explain the effect. H wasfound to be less potent than CO2 9 because it does notreadily permeate through the cell membrane. CO2 ,without an associated charge, is able to more rapidly
lower intracellular pH. This lead to the conclusion thatthe ®nal common pathway for CO2 vasomotor actionis the change of intracellular H in arteriolar smoothmuscle (Fig. 1).163
Prof. Gotoh felt his research could be extrapolated
to include human brain tissue and soon modi®ed his
continuous blood gas recorder to monitor humans. He
repeated his experiments on humans and veri®ed his®ndings.16,17,19,21,22,29,30,35 In 1965, he showed that
EEG slowing with hyperventilation was induced by
reduction of cerebral jugular venous oxygen tension(JpO2 ). This slowing occurred at JpO2 of 21:0 G 1:8
mmHg. Of the total decrease of JpO2 , 73% was due toreduction of blood ¯ow and 27% was secondary to the
Bohr effect.16
Continuing his novel monitoring techniques, Dr.
Gotoh developed ways to continuously check sodium,and potassium ion activities in monkeys.15 Utilizing the
Fick principle, 2.5% molecular hydrogen gas, and a

74

Amano T: Dr F Gotoh's contribution to neuroscienceTe¯on-coated hydrogen electrode, he found a new way
to evaluate cerebral blood ¯ow (CBF).23,24,27 Using his
technical skills, he revealed the results of pH, oxygen
tension, and carbon dioxide alterations in human volunteers and patients with seizures, altered mental status,
or cerebrovascular disease.
In addition, he studied metabolic activity during
periods of arousal and stimulation.12,31 The subsequent
decrement in JpO2 , increment in pCO2 , and fall in pH
suggested that metabolism is increased but no appreciable change in blood ¯ow results after arousal fromthe drowsy state. Dr. Gotoh and his fellow researchers
found that increase in CBF was delayed approximately
20 seconds for cutaneous pinpricks, 60 s for auditory
stimulation or arousal, and 240 s for photic stimulation.
Increased cerebral metabolism from increased mental
activity had only been described once before by Kety.
The changes went far to explain the reactive hyperemia resulting from carbon dioxide, a metabolic byproduct. This coupling of cerebral metabolism & blood¯ow is important in the cerebral circulatory homeostasis in both man and animals. Along with these studies, Prof. Gotoh worked on Cheyne-Stokes respiration
using polygraphic recordings.36 He concluded that
it was a neurogenically-mediated mechanism, which
results from depression of the respiratory center. Periods of apnea ensue with a delayed rise in PaCO2 , which
normally incites the respiratory center.
1970±1988: Cerebral Blood Flow Autoregulation
After an encounter in 1970 with a patient who had
Shy-Drager syndrome, Prof. Gotoh began to investigate
the importance of the autonomic nervous system (ANS)
in regulating CBF. Until this period, the ANS wasthought, most notably by Lassen & Sokoloff,162±164 toplay a minor role in CBF regulation. Dr. Gotoh recognized, however, that episodic syncope associated withorthostatic hypotension in Shy-Drager was most likely
due to dysautoregulation. Using this patient as a model,
global and regional CBF was determined by using N2 O
& 133 Xe injections in conjunction with continuous cerebral blood gas measurements. The results were as follows:39 a. Loss of autoregulation coincided with abnormality in the ANS. b. The degree of impairment wasdependent on the extent of the ANS dysfunction. c.
CBF response to CO2 was spared despite total dysautoregulation.
This data was presented at the 5th International
Symposium of Cerebral Blood Flow and Metabolism inRome in 1971.39 These ®ndings stressed the participation of the ANS in CBF regulation. Following Dr.
Gotoh's revolutionary work, many researchers produced data to verify his theories. He revealed that thechemical (CO2 ) & neurogenic (ANS) modalities oper-

Fig. 2

Dual control of cerebral artery.163

ated by independent pathways to exert control on the
CBF.
This paradigm was cemented by photography of pialarteries 15 to 200 microns in diameter during concurrent hyperventilation of 5% CO2 with iatrogenic induction of hypotension (by blood withdrawal).
Although blood pressure ¯uctuations had more
pronounced effects on arteries greater than 50 microns,
the converse was true for CO2 alterations. There wasgreater response in arteries less than 50 microns to CO2
inhalation or hyperventilation.44 This elegant demonstration by Dr. Gotoh is illustrated in Fig. 2.163 He also
showed that the ANS was also important in cat CBF
regulation.
Pial artery studies were continued using bipolar
platinum electrodes and high sensitive preampli®ers todetect action potentials.56 Induction of hypotension byblood withdrawal was shown to change the potentials
across the membrane.59 These recordings lent evidence
to Prof. Gotoh's concepts of ANS-CBF interactions.59
With every answer, however, came more questions.
These ®ndings only sparked more interest in CBF
maintenance.
He began studying the adrenergic & cholinergic systems separately. Furthermore, he discovered that every
neurotransmitter, such as VIP, DA, and cGRP, was a
candidate for further research. Through his research
he uncovered derangements related to the ANS in themechanisms associated with migraines.
1985±Present: Endothelial Contribution to
CBF-Importance of Nitric Oxide
It was Furchgott167,168 who ®rst took steps to dispel
the mystery of endothelial role in vasodilatation of theperipheral vessels.94,104 Prof. Gotoh expanded on thisresearch by implementing ultraviolet ray damage on

Keio J Med 2001; 50 (2): 72±80

Fig. 3

Endothelial control of cerebral artery (F Gotoh, 1990).
NO: Nitric Oxide.

endothelium, which impaired neurogenic (ANS) control of CBF. Despite this, chemical (CO2 ) modulation
remained intact.104
Following the discovery of nitric oxide endovascularly by Monchada et al.,169,170 Prof. Gotoh discovered
its effect on the cerebral circulation for the ®rst time.155
Later, Dr. Gotoh uncovered the relative contributionof nitric oxide to CBF autoregulation.156,157 Some
researchers had dismissed the role of CO2 in CBF regulation and claimed that vasodilation was exclusively
derived from nitric oxide concentration. Dr. Gotoh,
however, showed that nitric oxide and CO2 exert theircontrol on arterial ¯ow through two independent pathways, because the CO2 response remained intact evenafter the inhibition of nitric oxide.156
Even after his retirement, he continues to investigate
factors such as nitric oxide with regard to cerebrovascular regulation (Fig. 3). During his investigations,
he stumbled upon the role of platelets and the vicious
cycle, which can be induced by platelet aggregation.14,127,128 This is one mechanism to explain the
progression of microvascular bed deterioration.

75

This task is an arduous one. The clinical signs andsymptoms of stroke are multifarious which makes it
hard to formulate quanti®able measures. Together,
they have developed novel scales by use of conjoint
analysis to calculate the relative weight of each item.158
The subcommittee headed by Dr. Gotoh publishedtheir quanti®able stroke scale in the of®cial journal of
the Japan Stroke Society,159,160 the Japanese Journalof Stroke. Subsequently, he organized the International
Workshop on the Stroke Scale in July of 2000,161 inviting many of the leading experts in the clinimetrics &scales from around the world. At the forefront of stroke
science, Prof. Gotoh and workshop attendants discussed the current scales available as well as the needfor a reliable, evidence-based, and quanti®able stroke
scale applicable globally. Included in this workshop was
discussion for the need for international cooperative
studies, which continued at the International Conference of the International Stroke Society in Melbourne,
which took place in November of 2000.
Dr. Gotoh and his colleagues' work culminated insubmission of stroke scales to the International Journalof Stroke in 2001.162 This ends the last chapter of thebook, which is still being written as Professor Emeritus
Fumio Gotoh of Keio University continues to be at theleading edge of neurological advancements. His contributions both past, present, and future are deeply
appreciated.

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1996±Present: Stroke Scale Development
Although there are numerous stroke scales available
with varying complexities, clinical dilemma arise because none are able to quantify the severity of cerebral
infarction and its residua. Together with other membersof the stroke scale subcommittee of the Japan Stroke
Society, Prof. Gotoh has taken initiative to develop aweighted scale, which transcends simply documenting
neurologic de®cits, level of consciousness, and psychological states but which will stratify patients intorisk categories, treatment algorithms, and prognostic
groups.158

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Gotoh F, Muramatsu F, Fukuuchi Y, Amano T, Okayasu H,
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New York, Elsevier, 1982; 13±19
Komatsumoto S, Gotoh F, Araki N, Gomi S: Noradrenergic
nervous dysfunction in migraine. In: Meyer JS, Lechner H,
Reivich M, Ott EO, eds, Cerebral Vascular Disease 4, Amsterdam, Oxford, Excerpta Medica 1982; 286±291
Suzuki N, Gotoh F, Koto A, Morita Y, Senda R: Effect ofsuperior cervical ganglionectomy on synaptic vesicles in the
cerebral arterial wall. In: Benzi G, Giuffrida Stella AM,
Bachelard HS, Agnoli A, eds, Energy Transduction and Neurotransmission. Milano, Fondazione Internazionale Menarini,
1982; 208
Tachibana H, Gotoh F, Ishikawa Y: Retinal vascular autoregulation in normal subjects. Stroke 1982; 13: 149±155
Tomita M, Gotoh F, Sato T, Tanahashi N, Tanaka K, Kobari
M: The vertebral arterial system in rhesus monkeys is less ef®cient in autoregulation of blood ¯ow than the internal carotid
arterial system. In: Meyer JS, Lechner H, Reivich M, Ott EO,
eds, Cerebral Vascular Disease 4, Amsterdam, Excerpta
Medica 1982; 48±52
Tomita M, Gotoh F, Tanahashi N, Tanaka K, Kobari M: Ipsilateral increase in CBV by unilateral severing of the cervicalsympathetic preganglionic ®ber in cats. In: Heisted DD, Marcus
ML, eds, Cerebral blood ¯ow: Effects of Nerves and Neurotransmitters. New York, Elsevier, 1982; 403±408
Tomita M, Gotoh F, Tanahashi N, Tanaka K, Kobari M:
Photoelectric method for studying the intraparenchymal circulation. In: Tsuchiya M, Asano M, Oda M, eds, Basic Aspects ofMicrocirculation, Amsterdam, Excerpta Medica 1982; 61±74
Tomita M, Gotoh F: Which circulates faster through the cerebral microcirculatory system, red cells or plasma? Stroke 1982;
13: 722
Amano T, Gotoh F, Muramatsu F, Fukuuchi Y, Suzuki N,
Kobari M, Uematsu D, Obara K: Comparison between pialarteries and intraparenchymal vessels in response to stimulationof superior cervical ganglion. J Cereb Blood Flow Metab 1983;
3 (Suppl 1): S172±S173
Gomi S, Gotoh F, Ebihara S, Komatsumoto S, Araki N: CBF
autoregulation and autonomic nervous function in stroke. 6th
Asian and Oceanian Congress of Neurology. Excerpta Medica
Asian Paci®c Congress Series no. 22, 1983; 117±118
Tomita M, Gotoh F, Amano T, Tanahashi N, Kobari M,
Shinohara T, Mihara B: Redistribution of blood ¯ow between
the intra and extracranial arterial systems on induced hypotension within the autoregulatory range in cats. J Cereb Blood
Flow Metab 1983; 3 (Suppl 1): S644±S645

78
83. Amano T, Gotoh F, Tomita M, Tanahashi N, Kobari M,
Shinohara T, Mihara B: Hemodynamic changes in feline sensorimotor cortices and autonomic nerve activity during penicillin-induced seizures. In: Baldy-Moulinier M, Ingvar DH,
Meldrum BS, eds, Cerebral Blood Flow, Metabolism and Epilepsy, London, John Libbey 1983; 135±141
84. Gotoh F, Muramatsu F, Fukuuchi Y, Amano T, Tanaka K:
Neurogenic and chemical in¯uences on the diameter of pialveins. In: Auer LM, Loew F, eds, The Cerebral Veins, An Experimental and Clinical Update, Wien, Springer-Verlag, 1983;
179±186
85. Kobari M, Gotoh F, Tomita M, Tanahashi N, Tanaka K: Vulnerability of cerebral venous ¯ow following middle cerebral
arterial occlusion in cats. In: Auer LM, Loew F, eds, The Cerebral Veins, An Experimental and Clinical Update, Wien,
Springer-Verlag, 1983; 287±291
86. Komatsumoto S, Gotoh F, Shimazu K, Ichijo M, Yamashita K,
Araki N, Hamada J: Autonomic nervous action potential of
cerebral veins. In: Auer LM, Loew F, eds, The Cerebral Veins,
An Experimental and Clinical Update, Wien, Springer-Verlag,
1983; 173±17887. Tachibana H, Gotoh F, Ebihara S, Okayasu H, Kitagawa Y,
Hata T, Suzuki N, Araki N: Prognostic value of cerebral blood¯ow autoregulation in the long-term prognosis of ischemic cerebrovascular disease. J Neurol Sci 1983; 60: 197±204
88. Tomita M, Gotoh F, Amano T, Tanahashi N, Kobari M,
Shinohara T, Mihara B: Transfer function through regional
cerebral cortex evaluated by a photoelectric method. Am J
Physiol 245: H385±H398, 1983
89. Gotoh F, Komatsumoto S, Araki N, Gomi S: Noradrenergic
nervous activity in migraine. Arch Neurol 1984; 41: 951±955
90. Kobari M, Gotoh F, Fukuuchi Y, Tanaka K, Suzuki N,
Uematsu D: Blood ¯ow velocity in the pial arteries of cats, withparticular reference to the vessel diameter. J Cereb Blood Flow
Metab 1984; 4: 110±114
91. Tanahashi N, Gotoh F, Tomita M, Amano T, Kobari M, Shinohara T, Mihara B: Effect of aging on reactive hyperemia following reopening of occluded middle cerebral artery in cats.
Monogr Neural Sci 1984; 11: 40±46
92. Araki N, Gotoh F, Shimazu K, Komatsumoto S, Ichijo M,
Hamada J: Role of the vagus and the nucleus basalis of Meynert in neurogenic regulation of the cerebral vessels. J Cereb
Blood Flow Metab 1985; 5 (Suppl 1): 517±518
93. Gogolak I, Gotoh F, Tomita M, Tanahashi N, Kobari M,
Shinohara T, Mihara B: No intracerebral steal phenomenon in
the ischemic brain following papaverine administration. Stroke
1985; 16: 114±117
94. Gotoh F, Fukuuchi Y, Amano T, Tanaka K, Suzuki N, Uematsu
D, Kawamura J, Yamawaki T, Turcani P: Visualization of platelet aggregation in the pial vessels in situ: effect of middle cerebral artery occlusion. J Cereb Blood Flow Metab 1985; 5(Suppl 1): S381±382
95. Hamada J, Gotoh F, Ishikawa Y, Komatsumoto S, Araki N,
Gomi S: Autonomic nervous function in migraine: quantitative
determination of perspiration and retinal vasomotor activity.
Cephalalgia 1985; 5 (Suppl 3): 460±461
96. Tomita M, Gotoh F, Tanahashi N, Kobari M, Shinohara T,
Mihara B: Role of the osmotic potential in the development ofcytotoxic edema. Acta Neurol Scand 1985; (Suppl) 72: 113±
114
97. Kobari M, Gotoh F, Fukuuchi Y, Amano T, Suzuki N, Uematsu
D, Obara K, Gogolak I, Sandor P: Effects of (D-Met2, Pro5)enkephalinamide and naloxone on pial vessels in cats. J Cereb
Blood Flow Metab 1985; 5: 34±3998. Kobari M, Gotoh F, Tomita M, Shinohara T, Terayama Y,
Mihara B, Turcani P: ``CO2 type'' and ``papaverine type''

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increases in cerebrocortical blood ¯ow with respect to microvascular ¯ow pattern. In: Tsuchiya M, Asano M, Oda M, Okazaki I, eds, Microcirculation Annual, Amsterdam, Excerpta
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Tomita M, Gotoh F, Kobari M, Shinohara T, Terayama Y,
Mihara B, Turcani P: Restriction of cellular swelling and spontaneous increase in the osmolality of the intracellular ¯uid in a
simplistic cell model. In: Inaba Y, Klatzo I, Spatz M, eds, Brain
Edema, Berlin, Springer Verlag, 1985; 245±249
Uematsu D, Gotoh F, Fukuuchi Y, Kobari M, Kawamura J,
Obara K, Itoh N: Comparison between pial and intraparenchymal vascular responses to superior cervical ganglion stimulation during hypercapnia. J Cereb blood Flow Metab 1985; 5(Suppl 1): S497±S498
Gotoh F, Fukuuchi Y, Amano T, Tanaka K, Uematsu D,
Suzuki N, Kobari M, Obara K: Comparison between pial andintraparenchymal vascular responses to cervical sympathetic
stimulation in cats. Part I. Under normal resting conditions.
J Cereb Blood Flow Metab 1986; 6: 342±347
Gotoh F, Fukuuchi Y, Koto A, Amano T, Tanaka K, Suzuki N,
Uematsu D, Morita Y: Distribution of nerve terminals andvasomotor responses to feline pial veins as compared with pialarteries. In: Owman C, Hardebo JE, eds, Neural Regulation ofBrain Circulation, Amsterdam, Elsevier Science, 1986; 515±528
Sandor P, Gotoh F, Tomita M, Tanahashi N, Gogolak I: Effects
of a stable enkephalin analogue, (D-Met2, Pro5)-enkephalinamide, and naloxone on cortical blood ¯ow and cerebral blood
volume in experimental brain ischemia in anesthetized cats.
J Cereb Blood Flow Metab 1986; 6: 553±558
Gotoh F, Fukuuchi Y, Amano T, Tanaka K, Uematsu D,
Suzuki N, Kawamura J, Yamawaki T, Itoh N, Obara K: Role ofEndothelium in Responses of Pial Vesels to Changes in Blood
Pressure and to Carbon Dioxide in Cats. J Cereb Blood Flowand Metabol 1987; 7 (Suppl 1): S275
Gotoh F, Ebihara S, Hata, Shinohara T, Terayama Y, Kawamura J, Takashima S: Local cerebral blood ¯ow and CO2
responsiveness in patients with ``Moyamoya Disease''. In:
Meyer JS, Lechner H, Reivich M, Ott EO, eds, Cerebral Vascular Disease 6, Amsterdam, Excerpta Medica, 1987; 97±102
Gotoh F, Koto A, Tanaka K, Suzuki N, Uematsu D, Kawamura
J, Yamawaki T: Rheological behavior of platelets in situ in
middle cerebral artery occlusion. In: Hartmann A, Kuschinsky
W, eds, Cerebral Ischemia and Hemorheology, Berlin,
Springer-Verlag, 1987; 222±232
Hamada J, Gotoh F, Shimazu K, Komatsumoto S, Ichijo M,
Araki N, Ohta K: Role of the trigeminal ganglion in neurogenic
regulation of the cerebral vessels. J Cereb Blood Flow Metab
1987; 7 (Suppl 1): S232
Kobari M, Gotoh F, Fukuuchi Y, Tanaka K, Suzuki N,
Uematsu D: Quantitative measurement of blood ¯ow velocity
in feline pial arteries during hemorrhagic hypotension andhypercapnia. Stroke 1987; 18: 457±463
Koto A, Gotoh F, Suzuki N, Morita Y, Naganuma Y, Isozumi
K, Senda R: Quantitative analysis of changes in perivascularnerve terminals of the cerebral vessel: effects of stimulation of
the superior cervical ganglion or inhibition of dopamine-bhydroxylase. J Cereb Blood Flow Metab 1987; 7 (Suppl 1): S231
Koto A, Gotoh F, Suzuki N, Morita Y, Isozumi K, Senda R:
Changes in the adrenergic nervous system of cerebral vessels
after experimental subarachnoid hemorrhage. In: CervosNavarro J, Ferszt R, eds, Stroke and Microcirculation, New
York, Raven Press, 1987; 457±464
Tanaka K, Gotoh F, Gomi S, Takashima S, Mihara B: Validityof the operational equation of the 14C-deoxyglucose methodmodi®ed for changing arterial plasma glucose level. Keio J Med
1987; 36: 217±222Keio J Med 2001; 50 (2): 72±80112. Tanaka K, Gotoh F, Ishihara N, Gomi S, Takashima S, Mihara
B: Behavior and local cerebral glucose metabolism in rats withlesion of nucleus basalis magnocellularis. J Cereb Blood Flow
Metab 1987; 7 (Suppl 1): S380
113. Terayama Y, Gotoh F, Tomita M, Tanahashi N, Kobari M,
Shinohara T, Mihara B, Ohta K: Continuous recording of focal
edema of the cerebral cortex in vivo using sonomicrometry. In:
Cervos-Navarro J, Ferszt R, eds, Stroke and Microcirculation,
New York, Raven Press, 1987; 263±269
114. Turcani P, Gotoh F, Tomita M, Tanahashi N, Kobari M, Terayama Y, Mihara B, Ohta K: Role of platelets and leukocytes inthe development of low perfusion hyperemia in the cerebral
ischemic area of cats. In: Meyer JS, Lechner H, Reivich M, Ott
EO, eds, Cerebral Vascular disease 6, Amsterdam, Excerpta
Medica, 1987; 285±289
115. Uematsu D, Gotoh F, Fukuuchi Y, Amano T, Suzuki N, Kobari
M, Kawamura J, Itoh N: Comparison between pial and intraparenchymal vascular responses to sympathetic stimulation
under hypercapnic conditions. With special reference to themechanism for escape phenomenon. J Neurol Sci 1987; 78: 303±
311
116. Kawamura J, Gotoh F, Fukuuchi Y, Amano T, Tanaka K,
Uematsu D, Suzuki N, Kobari M, Obara K: Effects of the
new calcium antagonist 2-nitratopropyl 3-nitratopropyl 2,6dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicalboxylate on cerebral circulation in cats. Arzneimittelforschung
1988; 38: 221±224117. Kobari M, Gotoh F, Tomita M, Tanahashi N, Shinohara T,
Terayama Y, Mihara B: Bilateral hemispheric reduction of
cerebral blood volume and blood ¯ow immediately after experimental cerebral hemorrhage in cats. Stroke 1988; 19: 991±996118. Tanaka K, Gotoh F, Fukuuchi Y, Amano T, Suzuki N, Uematsu
D, Kawamura J, Yamawaki T, Itoh N, Obara K: Stable prostacyclin analogue preventing microcirculatory derangement inexperimental cerebral ischemia in cats. Stroke 1988; 19: 1267±
1274
119. Tanaka K, Gotoh F, Gomi S, Takashima S, Mihara B: In¯uenceof cerebral circulation on measurement of the cerebral glucose
metabolic rate by 14C-deoxyglucose method. Keio J Med 1988;
37: 132±143120. Tanaka K, Gotoh F, Ishihara N, Gomi S, Takashima S, Mihara
B: Autoradiographic analysis of second-messenger systems in
the gerbil brain. Brain Res Bull 1988; 21: 693±700
121. Tomita M, Gotoh F, Tanahashi N, Kobari M, Terayama Y,
Mihara B, Ohta K, Gerdsen I: Comparison between the photoelectric method and H2 clearance method for measuring cerebrocortical blood ¯ow in cats. J Cereb Blood Flow Metab 1988;
8: 727±732
122. Turcani P, Gotoh F, Ishihara N, Tanaka K, Gomi S, Takashima
S, Mihara B: Are blood platelets involved in the pathogenesis
of ischemic brain edema in gerbils? Stroke 1988; 19: 486±489123. Gotoh F, Tanaka K: Regulation of cerebral blood ¯ow. In:
Bruyn GW, Vinken PJ, eds, Handbook of Clinical Neurology.
Volume 53, Revised Series 9, Vascular Diseases Part 1, Chapter
3. Amsterdam, Elsevier, 1988; 47±77124. Fukuuchi Y, Gotoh F, Izumi K, Isozumi K, Imai A: Role of thesympathetic system in cerebrovascular CO2 responsivenessduring hypoglycemia. J Cereb Blood Flow Metab 1989; 9(Suppl 1): S488
125. Gomi S, Gotoh F, Ishihara N, Tanaka K, Ishikawa Y, Takashima S, Mihara B: Unilateral lesion of the nucleus basalis
magnocellularis does not impair autoregulation of local cerebral blood ¯ow in rats. In: Seylaz J, Mackenzie ET, eds,
Neurotransmission and Cerebrovascular Function I, Amsterdam, Excerpta Medica, 1989; 389±392
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Hamada J: Sweating function and retinal vasomotor reactivity
in migraine. Cephalalgia 1989; 9: 179±185
Gotoh F, Fukuuchi Y, Amano T, Tanaka K, Kawamura J,
Yamawaki T, Ito N, Obara K, Muramatsu K, Takahashi K: The
effects of inhibition of thromboxane A2 synthetase on theinteraction between platelets and the cerebral vessel wall inexperimental middle cerebral artery occlusion. In: Meyer JS,
et al., eds, Cerebral Vascular Disease 7, Amsterdam, Elsevier,
1989; 263±268
Gotoh F, Fukuuchi Y, Amano T, Tanaka K, Kawamura J,
Yamawaki T, Obara K, Ito N: Effects of tissue plasminogenactivator on microcirculation and size of infarction following
MCA occlusion in cat. J Cereb Blood Flow Metab 1989; 9(Suppl 1): S9
Gotoh F, Fukuuchi Y, Shinohara T, Takashima S, Terayama Y,
Kawamura J, Takahashi K: The effect of intravenous glycerol
on deep brain circulation in patients with acute intracerebral
hemorrhage. In: Meyer JS et al., eds, Cerebral Vascular Disease
7, Amsterdam, Elsevier, 1989; 193±196
Isozumi K, Gotoh F, Fukuuchi Y, Koto A, Izumi Y, Tsuzuki Y,
Senda R: Effect of hypoglycemia on autonomic nerve terminalsof cerebral arteries. Neurotransmission and cerebrovascularfunction I 1989; 163±166
Komatsumoto S, Gotoh F, Shimazu K, Ichijo M, Araki N,
Hamada J, Ohta K, Takahashi S: Role of Locus Ceruleus on
cerebral hemodynamic changes induced by hypercapnia. J
Cereb Blood Flow Metab 1989; 9 (Suppl 1): S478
Mihara B, Gotoh F, Tomita M, Tanahashi N, Shinohara T,
Terayama Y, Ohta K, Fujiwara T: Morphological changes of
cerebral microcirculatory system in the brain swelling of vascular origin. In: Asano M, et al., eds, Microcirculation Annual
1989, Tokyo, Nihon-Igakukan, 1989; 49±50
Nakamura K, Tukatani Y, Kubo A, Hashimoto S, Terayama Y,
Amano T, Gotoh F: The behavior of 99mTc-hexamethylpropyleneamineoxime (99m-Tc-HMPAO) in blood and brain. Eur J
Nucl Med 1989; 15: 100±107
Ohta K, Gotoh F, Shimazu K, Komatsumoto S, Ichijo M, Araki
N, Hamada J: Neuronal activity in the locus caeruleus responds
to cerebral hemodynamic changes induced by hypercapnia.
J Auton Nerv Sys 1989; 29: 72±73
Tanaka K, Gotoh F, Fukuuchi Y, Amano T, Uematsu D,
Kawamura J, Yamawaki T, Itoh N, Obara K, Muramatsu K:
Effects of a selective inhibitor of cyclic AMP phosphodiesteraseon the pial microcirculation in feline cerebral ischemia. Stroke
1989; 20: 668±673
Tanaka K, Gotoh F, Fukuuchi Y, Amano T: Prostacyclin inexperimental ischemic models. Stroke 1989; 20: 698±699
Tanaka K, Gotoh F, Gomi S, Takashima S, Mihara B: Regional
alteration of second-messenger systems in the ischemic gerbil
brain. J Cereb Blood Flow Metab 1989; 9 (Suppl 1): S99
Tomita M, Gotoh F, Tanahashi N, Kobari M, Shinohara T,
Terayama Y, Mihara B, Ohta K: Diffusion of oxygen andhydrogen gas is faster through a layer of suspended cultured C6
cells than through the medium. In: Piiper J, Goldstick TK,
Meyer M, eds, Oxygen Transport to Tissue XII, New York,
Plenum Press, 1990; 115±120
Tomita M, Gotoh F, Tanahashi N, Shinohara T, Terayama Y,
Mihara B, Ohta K: Indicator dilution curves and heterogeneityin tissue perfusion: analysis of a microvascular model. In:
Asano M, et al., eds, Microcirculation Annual 1989, Tokyo,
Nihon-Igakukan, 1989; 7±8
Tomita M, Gotoh F, Tanahashi N, Shinohara T, Terayama Y,
Mihara B, Ohta K: Spontaneous periodic ¯uctuation of CVD
induced by anti-platelet serum and abolished by middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab 1989; 9(Suppl 1): S457

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141. Tomita M, Gotoh F: Functional interpretation of tissue indicator dilution curves and its veri®cation. Int J Microcirc 1989; 8(Suppl 1): S33
142. Mihara B, Gotoh F, Tomita M, Tanahashi N, Kobari M,
Shinohara T, Yamawaki T, Ohta K, Takeda H: Cerebral
hemodynamic changes after cardiac arrest in cats. In: Meyer
JS, Lechner H, Toole JF, eds, Cerebral Vascular Disease 8,
Amsterdam, Excerpta Medica, 1991; 39±42143. Ohta K, Gotoh F, Tomita M, Tanahashi N, Kobari M, Shinohara T, Terayama Y, Mihara B: Effect of glycerol on the
hemodynamics of acutely induced ischemic area in the cerebral
cortex of cats. Adv in Neurol 1990; 52: 275±284144. Takashima S, Gotoh F, Ishihara N, Tanaka K, Gomi S, Mihara
B: Autoradiographic studies on stress-induced alteration in
adenylate cyclase activity in the gerbil brain. Neurochem Res
1990; 15: 324
145. Tomita M, Gotoh F, Shinohara T: Ionic concentration shifting¯uid during glutamate-induced swelling of cultured glioma cells
estimated by the cytocrit technique. Adv Neurol 1990; 52: 558
146. Tomita M, Gotoh F, Tanahashi N, Kobari M, Shinohara T,
Yamawaki T, Terayama Y, Mihara B, Ohta K, Takeda H: RBC
aggregation is not a primary factor for microvascular stasis on
temporary complete ischemia of the feline brain. In: Hartmann
A, Kuschinsky W, Hoyer S, eds, Cerebral Ischemia and
Dementia. Berlin, Springer-Verlag, 1991; 187±192147. Tomita M, Gotoh F, Tanahashi N, Kobari M, Shinohara T,
Yamawaki T, Ohta K, Matsuoka S, Takeda H: Residual oxygen
metabolism in completely ischemic tissue of the cat brain: apolarographic method for measuring ¯ow and metabolism
in the microregion. In: Ito U, Kirino T, Kuroiwa T, Klatzo I,
eds, Maturation Phenomenon in Cerebral Ischemia, Berlin,
Springer-Verlag, 1990; 185±193148. Gotoh F, Fukuuchi Y, Koto A, Amano T, Naganuma Y, Ito N,
Obara K, Muramatsu K, Takahashi K, Fujiwara T, Senda R:
Correlation between ultraviolet induced endothelial damage,platelet aggregation, microcirculatory disturbance and bloodbrain barrier breakdown. In: Johansson BB, Owman Ch,
Widner H, eds, Pathophysiology of the Blood-brain Barrier,Amsterdam, Elsevier Science Publishers BD, 1990; 343±356
149. Tomita M, Gotoh F: Capillary recruitment of the cerebral
cortex during CO2 inhalation: fact or illusion? J Cereb Blood
Flow Metab 1990; 10: 294
150. Gotoh F, Fukuuchi Y, Amano T, Uematsu D, Yamawaki T, Ito
N, Obara K, Muramatsu K, Shirai T, Takahashi K, Gotoh J:
Effects of endothelin on feline cerebral microcirculation. In:
Meyer JS, Lechner H and Toole J, eds, Cerebral Vascular Disease 8, Amsterdam, Excerpta Medica, 1991; 191±195151. Gomi S, Gotoh F, Ishihara N, Tanaka K, Ishikawa Y,
Takashima S, Mihara B: Effects of lesioning of the substantia
innominata on autoregulation of local cerebral blood ¯ow inrats. J Cereb Blood Flow Metab 1991; 11: 66±71
152. Ohta K, Gotoh F, Shimazu K, Amano T, Komatsumoto S,
Hamada J, Takahashi S: Locus coeruleus stimulation exerts
different in¯uences on the dynamic changes of cerebral pial andintraparenchymal vessels. Neurol Res 1991; 13: 164±167

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cerebrovascular neurogenic vasodilatation in the rat. Clin
Auton Res 1991; 1: 23±26154. Tanaka K, Gotoh F, Gomi S, Takashima S, Mihara B: Autoradiographic analysis on second-messenger systems and local
cerebral blood ¯ow in ischemic gerbil brain. J Cereb Blood
Flow Metab 1991; 11: 283±291
155. Gotoh F, Fukuuchi Y, Amano T, Yamawaki T, Itoh N,
Muramatsu K, Shirai T, Takahashi K, Gotoh J: Role of endothelium-derived relaxing and contracting factors in feline cerebral microcirculation. Stroke 1991; 22: 144
156. Amano T, Fukuuchi Y, Yamawaki T, Obara K, Muramatsu K,
Shirai T, Takahashi K, Gotoh J, Gotoh F: Does nitric oxide
participate in CO2 reactivity of cerebral vessels? J Cerebral
Blood Flow and Metabol 1993; 13 (Suppl 1): S137
157. Amano T, Fukuuchi Y, Obara K, Muramatsu K, Shirai T,
Takahashi K, Gotoh J, Gotoh F: Nitric Oxide is involved in
autoregulatory response of feline cerebral artery. J Stroke andCerebrovasc Disease 1996; 6 (Suppl 1): 29±34158. Terayama Y, Gotoh F, Amano T: A preliminary study
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