J.B. Springborg et al
EPO normalizes CBF autoregulation after SAH
829
HERTZ, M.M., BARRY, D.I., HEMMINGSEN, R. & BOLWIG, T.G.
(
ment of cerebral blood ¯ow (CBF) in rats: evaluation of the eect
of bolus volume. Acta Physiol Scand., 122, 397 ± 400.
HIRASHIMA, Y., NAKAMURA, S., ENDO, S., KUWAYAMA, N.,
SAKANAKA, M., WEN, T.C., MATSUDA, S., MASUDA, S., MORISHI-
TA, E., NAGAO, M. & SASAKI, R. (1998). In vivo evidence that
erythropoietin protects neurons from ischemic damage. Proc.
Natl. Acad. Sci. U.S.A., 95, 4635 ± 4640.
1984). The intracarotid 133xenon injection method for measure-
SAYAMA, T., SUZUKI, S. & FUKUI, M. (1998). Expression of
NARUSE, Y.
&
TAKAKU, A. (1997). Elevation of platelet
inducible nitric oxide synthase in rats following subarachnoid
hemorrhage. Neurol. Res., 20, 79 ± 84.
activating factor, in¯ammatory cytokines, and coagulation
factors in the jugular vein of patients with subarachnoid
hemorrhage. Neurochem. Res., 22, 1249 ± 1255.
SAYAMA, T., SUZUKI, S. & FUKUI, M. (1999). Role of inducible
nitric oxide synthase in the cerebral vasospasm after subar-
achnoid hemorrhage in rats. Neurol. Res., 21, 293 ± 298.
SCHMIDT, J.F., WALDEMAR, G., VORSTRUP, S., ANDERSEN, A.R.,
GJERRIS, F. & PAULSON, O.B. (1990). Computerized analysis of
cerebral blood ¯ow autoregulation in humans: validation of a
method for pharmacologic studies. J. Cardiovasc. Pharmacol.,
15, 983 ± 988.
JUUL, S.E., ANDERSON, D.K., LI, Y. & CHRISTENSEN, R.D. (1998).
Erythropoietin and erythropoietin receptor in the developing
human central nervous system. Pediatr. Res., 43, 40 ± 49.
KENDALL, M.G. & STUART, A., (eds) (1958). The advanced theory of
statistic. pp. 141 ± 165 New York, NY: Hafner.
KIKUCHI, T., OKUDA, Y., KAITO, N. & ABE, T. (1995). Cytokin
production in cerebrospinal ¯uid after subarachnoid haemor-
rhage. Neurol. Res., 17, 106 ± 108.
SCHWARTZ, D., MENDONCA, M., SCHWARTZ, I., XIA, Y., SATRIA-
& BLANTZ, R.C. (1997). Inhibition of
NO, J., WILSON, C.B.
KONISHI, Y., CHUI, D.H., HIROSE, H., KUNISHITA, T. & TABIRA, T.
(
constitutive nitric oxide synthase (NOS) by nitric oxide generated
by inducible NOS after lipopolysaccharide administration
provokes renal dysfunction in rats. J. Clin. Invest., 100, 439 ± 448.
1993). Trophic eect of erythropoietin and other hematopoietic
factors on central cholinergic neurons in vitro and in vivo. Brain
Res., 609, 29 ± 35.
SCOTT, J.A.
& MCGORMACK, D.G. (1999). Selective in vivo
KUSANO, E., AKIMOTO, T., INOUE, M., MASUNAGA, Y. UMINO, T.,
ONO, S., ANDO, Y., HOMMA, S., MUTO, S., KOMATSU, N. &
ASANO, Y. (1999). Human recombinant erythropoietin inhibits
interleukin-1beta-stimulated nitric oxide and cyclic guanosine
monophosphate production in cultured rat vascular smooth-
muscle cells. Nephrol. Dial. Transplant., 14, 597 ± 603.
inhibition of inducible nitric oxide synthase in a rat model of
sepsis. J. Appl. Physiol., 86, 1739 ± 1744.
SHEEHY, A.M., BURSON, M.A. & BLACK, S.M. (1998). Nitric oxide
exposureinhibitsendothelialNOSactivitybutnotgeneexpression:
a role for superoxide. Am. J. Physiol., 274, L833 ± L841.
SIREN, A.L., FRATELLI, M., BRINES, M., GOEMANS, C., CASA-
GRANDE, S., LEWCZUK, P., KEENAN, S., GLEITER, C., PASQUA-
LI, C., CAPOBIANCO, A., MENNINI, T., HEUMANN, R., CERAMI,
LASSEN, N.A. (1968). Brain extracellular pH: the main factor
controlling cerebral blood ¯ow. Scand. J. Clin. Invest., 22,
2
47 ± 251.
A., EHRENREICH, H. & GHEZZI, P. (2001). Erythropoietin
LIPTON, P. (1999). Ischemic cell death in brain neurons. Physiol.
Rev., 79, 1431 ± 1568.
LUFT, F.C. (2000). Erythropoietin and arterial hypertension. Clin.
Nephrol., 53, S61 ± S64.
prevents neuronal apoptosis after cerebral ischemia and meta-
bolic stress. Proc. Natl. Acad. Sci. U.S.A., 98, 4044 ± 4049.
SOBEY, C.G. & FARACI, F.M. (1998). Subarachnoid haemorrhage:
what happens to the cerebral arteries? Clin. Exp. Pharmacol.
Physiol., 25, 867 ± 876.
MA, X., WILLUMSEN, L., HAUERBERG, J., PEDERSEN, D.B.
&
JUHLER, M. (2000). Eects of graded hyperventilation on
cerebral blood ¯ow autoregulation in experimental subarachnoid
hemorrhage. J. Cereb. Blood Flow Metab., 20, 718 ± 725.
MARTI, H.H., WENGER, R.H., RIVAS, L.A., STRAUMANN, U.,
DIGICAYLIOGLU, M., HENN, V., YONEKAWA, Y., BAUER, C. &
GASSMANN, M. (1996). Erythropoietin gene expression in
human, monkey and murine brain. Eur. J. Neurosci., 8, 666 ± 676.
MASUDA, S., OKANO, M., YAMAGISHI, K., NAGAO, M., UEDA, M. &
SASAKI, R. (1994). A novel site of erythropoietin production.
Oxygen-dependent production in cultured rat astrocytes. J. Biol.
Chem., 269, 19488 ± 19493.
SQUADRITO, F., ALTAVILLA, D., SQUADRITO, G., CAMPO, G.M.,
ARLOTTA, M., QUARTARONE, C., SAITTA, A. & CAPUTI, A.P.
(1999). Recombinant human erythropoietin inhibits iNOS
activity and reverts vascular dysfunction in splanchnic artery
occlusion shock. Br. J. Pharmacol., 127, 482 ± 488.
TUOR, U.I., EDVINSSON, L. & MCCULLOCH, J. (1986). Catechola-
mines and the relationship between blood ¯ow and glucose use.
Am. J. Physiol., 251, H824 ± H833.
VOLDBY, B., ENEVOLDSEN, E.M. & JENSEN, F.T. (1985). Cerebro-
vascular reactivity in patients with ruptured intracranial
aneurysms. J. Neurosurg., 62, 59 ± 67.
MATHIESEN, T., EDNER, G., ULFARSSON, E. & ANDERSSON, B.
(
WELCH, B.L. (1947). The generalization of `student's' problem when
several dierent population variances are involved. Biometrica,
34, 28 ± 35.
1997). Cerebrospinal ¯uid interleukin-1 receptor antagonist and
tumor necrosis factor-alpha following subarachnoid hemorrage.
J. Neurosurg., 87, 215 ± 220.
WIDENKA, D.C., MEDELE, R.J., STUMMER, W., BISE, K. & STEIGER,
H.J. (1999). Inducible nitric oxide synthase: a possible key factor
in the pathogenesis of chronic vasospasm after experimental
subarachnoid hemorrhage. J. Neurosurg., 90, 1098 ± 1104.
YAMAJI, R., OKADA, T., MORIYA, M., NAITO, M., TSURUO, T.,
MIYATAKE, K. & NAKANO, Y. (1996). Brain capillary endothelial
cells express two forms of erythropoietin receptor mRNA. Eur. J.
Biochem., 239, 494 ± 500.
YAMAMOTO, M., KOSHIMURA, K., KAWAGUCHI, M., SOHMIYA,
M., MURAKAMI, Y. & KATO, Y. (2000). Stimulating eect of
erythropoietin on the release of dopamine and acetylcholine from
the rat brain slice. Neurosci. Lett., 292, 131 ± 133.
YAMAMOTO, S., NISHIZAWA, S., TSUKADA, H., KAKIUCHI, T.,
YOKOYAMA, T., RYU, H. & UEMURA, K. (1998). Cerebral blood
¯ow autoregulation following subarachnoid hemorrhage in rats:
chronic vasospasm shifts the upper and lower limits of the
autoregulatory range toward higher blood pressures. Brain Res.,
782, 194 ± 201.
MENDELOW, A.D. (1988). Pathophysiology of delayed ischaemic
dysfunction after subarachnoid haemorrhage: experimental and
clinical data. Acta Neurochir., 45 (Suppl): 7 ± 10.
MORISHITA, E., MASUDA, S., NAGAO, M., YASUDA, Y. & SASAKI, R.
(
1997). Erythropoietin receptor is expressed in rat hippocampal
and cerebral cortical neurons, and erythropoietin prevents in vitro
glutamate-induced neuronal death. Neuroscience, 76, 105 ± 116.
OLESEW, J. (1972). The eect of intra caroid epinephrine,
norepinephrine, and angiotensin on the regional cerebral blood
¯
ow in man. Neurology, 22, 978 ± 987.
OLESEN, J., PAULSON, O.B. & LASSEN, N.A. (1971). Regional cerebral
blood ¯ow in man determined by the initial slope of the clearance
of intra-arterially injected 133Xe. Stroke, 2, 519 ± 540.
PAULSON, O.B., STRANDGAARD, S.
Cerebral autoregulation. Cerebrovasc. Brain Metab. Rev., 2,
61 ± 192.
& EDVINSSON, L. (1990).
1
RASMUSSEN, G., HAUERBERG, J., WALDEMAR, G., GJERRIS, F. &
JUHLER, M. (1992). Cerebral blood ¯ow autoregulation in
experimental subarachnoid haemorrhage in rat. Acta Neurochir.
(Received August 30, 2001
Revised November 20, 2001
Accepted November 22, 2001)
(
Wien.), 119, 128 ± 133.
SADAMOTO, Y., IGASE, K., SAKANAKA, M., SATO, K., OTSUKA, H.,
SAKAKI, S., MASUDA, S. & SASAKI, R. (1998). Erythropoietin
prevents place navigation disability and cortical infarction in rats
with permanent occlusion of the middle cerebral artery. Biochem.
Biophys. Res. Commun., 253, 26 ± 32.
British Journal of Pharmacology vol 135 (3)