Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 27 September 1985:
Vol. 229. no. 4720, pp. 1397 - 1400
DOI: 10.1126/science.4035356
Prev | Table of Contents | Next

Articles

Science, Vol 229, Issue 4720, 1397-1400
Copyright © 1985 by American Association for the Advancement of Science

articles

Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications

RM Sapolsky and WA Pulsinelli

Sustained exposure to glucocorticoids, the adrenocortical stress hormones, is toxic to neurons, and such toxicity appears to play a role in neuron loss during aging. Previous work has shown that glucocorticoids compromise the capacity of neurons to survive a variety of metabolic insults. This report extends those observations by showing that ischemic injury to neurons in rat brain is also potentiated by exposure to high physiological titers of glucocorticoids and is attenuated by adrenalectomy. The synergy between ischemic and glucocorticoid brain injury was seen even when glucocorticoid levels were manipulated after the ischemic insult. Pharmacological interventions that diminish the adrenocortical stress response may improve neurological outcome from stroke or cardiac arrest.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dynamic regulation of mitochondrial function by glucocorticoids.
J. Du, Y. Wang, R. Hunter, Y. Wei, R. Blumenthal, C. Falke, R. Khairova, R. Zhou, P. Yuan, R. Machado-Vieira, et al. (2009)
PNAS 106, 3543-3548
   Abstract »    Full Text »    PDF »
Pneumococcal Meningitis in Taiwanese Children: Emphasis on Clinical Outcomes and Prognostic Factors.
M.-H. Tsai, S.-H. Chen, C.-Y. Hsu, D.-C. Yan, M.-H. Yen, C.-H. Chiu, Y.-C. Huang, and T.-Y. Lin (2008)
J Trop Pediatr 54, 390-394
   Abstract »    Full Text »    PDF »
Activation of Trk neurotrophin receptors by glucocorticoids provides a neuroprotective effect.
F. Jeanneteau, M. J. Garabedian, and M. V. Chao (2008)
PNAS 105, 4862-4867
   Abstract »    Full Text »    PDF »
Reparixin, an Inhibitor of CXCR2 Function, Attenuates Inflammatory Responses and Promotes Recovery of Function after Traumatic Lesion to the Spinal Cord.
A. Gorio, L. Madaschi, G. Zadra, G. Marfia, B. Cavalieri, R. Bertini, and A. M. Di Giulio (2007)
J. Pharmacol. Exp. Ther. 322, 973-981
   Abstract »    Full Text »    PDF »
Chronic Glucocorticoids Increase Hippocampal Vulnerability to Neurotoxicity under Conditions That Produce CA3 Dendritic Retraction But Fail to Impair Spatial Recognition Memory.
C. D. Conrad, K. J. McLaughlin, J. S. Harman, C. Foltz, L. Wieczorek, E. Lightner, and R. L. Wright (2007)
J. Neurosci. 27, 8278-8285
   Abstract »    Full Text »    PDF »
Maternal Exposure to Low Levels of Corticosterone during Lactation Protects the Adult Offspring against Ischemic Brain Damage.
P. Casolini, M. R. Domenici, C. Cinque, G. S. Alema, V. Chiodi, M. Galluzzo, M. Musumeci, J. Mairesse, A. R. Zuena, P. Matteucci, et al. (2007)
J. Neurosci. 27, 7041-7046
   Abstract »    Full Text »    PDF »
Neuroprotection from secondary injury by polyethylene glycol requires its internalization.
P. Liu-Snyder, M. P. Logan, R. Shi, D. T. Smith, and R. B. Borgens (2007)
J. Exp. Biol. 210, 1455-1462
   Abstract »    Full Text »    PDF »
Social buffering: relief from stress and anxiety.
T. Kikusui, J. T Winslow, and Y. Mori (2006)
Phil Trans R Soc B 361, 2215-2228
   Abstract »    Full Text »    PDF »
Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex.
R. M. de Pablos, R. F. Villaran, S. Arguelles, A. J. Herrera, J. L. Venero, A. Ayala, J. Cano, and A. Machado (2006)
J. Neurosci. 26, 5709-5719
   Abstract »    Full Text »    PDF »
From The Cover: Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury.
A. Gorio, L. Madaschi, B. Di Stefano, S. Carelli, A. M. Di Giulio, S. De Biasi, T. Coleman, A. Cerami, and M. Brines (2005)
PNAS 102, 16379-16384
   Abstract »    Full Text »    PDF »
Hypertension and Hypothalamo-Pituitary-Adrenal Axis Hyperactivity Affect Frontal Lobe Integrity.
S. M. Gold, I. Dziobek, K. Rogers, A. Bayoumy, P. F. McHugh, and A. Convit (2005)
J. Clin. Endocrinol. Metab. 90, 3262-3267
   Abstract »    Full Text »    PDF »
Anterior Cingulate, Gyrus Rectus, and Orbitofrontal Abnormalities in Elderly Depressed Patients: An MRI-Based Parcellation of the Prefrontal Cortex.
M. Ballmaier, A. W. Toga, R. E. Blanton, E. R. Sowell, H. Lavretsky, J. Peterson, D. Pham, and A. Kumar (2004)
Am J Psychiatry 161, 99-108
   Abstract »    Full Text »    PDF »
Dexamethasone in Adults with Bacterial Meningitis.
J. de Gans, D. van de Beek, and the European Dexamethasone in Adulthood Bacterial (2002)
N. Engl. J. Med. 347, 1549-1556
   Abstract »    Full Text »    PDF »
Social Stress Exacerbates Focal Cerebral Ischemia in Mice.
N. Sugo, P. D. Hurn, M. B. Morahan, K. Hattori, R. J. Traystman, and A. C. DeVries (2002)
Stroke 33, 1660-1664
   Abstract »    Full Text »    PDF »
Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders.
K. Pacak and M. Palkovits (2001)
Endocr. Rev. 22, 502-548
   Abstract »    Full Text »    PDF »
Dehydroepiandrosterone Sulfate Is Neuroprotective in a Reversible Spinal Cord Ischemia Model : Possible Involvement of GABAA Receptors Editorial Comment: Possible Involvement of GABAA Receptors.
P. A. Lapchak, D. F. Chapman, S. Y. Nunez, J. A. Zivin, and C. Y. Hsu (2000)
Stroke 31, 1953-1957
   Abstract »    Full Text »    PDF »
Distribution of Corticosteroid Receptors in the Rhesus Brain: Relative Absence of Glucocorticoid Receptors in the Hippocampal Formation.
M. M. Sanchez, L. J. Young, P. M. Plotsky, and T. R. Insel (2000)
J. Neurosci. 20, 4657-4668
   Abstract »    Full Text »    PDF »
Early Exclusive Use of the Affected Forelimb After Moderate Transient Focal Ischemia in Rats : Functional and Anatomic Outcome Editorial Comment: Functional and Anatomic Outcome.
S. T. Bland, T. Schallert, R. Strong, J. Aronowski, J. C. Grotta, and D. M. Feeney (2000)
Stroke 31, 1144-1152
   Abstract »    Full Text »    PDF »
The Corticosterone Synthesis Inhibitor Metyrapone Prevents Hypoxia/Ischemia-Induced Loss of Synaptic Function in the Rat Hippocampus Editorial Comment.
H. J. Krugers, S. Maslam, J. Korf, M. Joels, and F. Holsboer (2000)
Stroke 31, 1162-1172
   Abstract »    Full Text »    PDF »
Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest.
S. M. Langley, P. J. Chai, J. J. Jaggers, and R. M. Ungerleider (2000)
Eur. J. Cardiothorac. Surg. 17, 279-286
   Abstract »    Full Text »    PDF »
Gas Embolism.
C. M. Muth and E. S. Shank (2000)
N. Engl. J. Med. 342, 476-482
   Full Text »    PDF »
Is alpha-stat management still justified for deep hypothermic circulatory arrest in adults?.
T.-A. Miyamoto and K.-J. Miyamoto (1999)
J. Thorac. Cardiovasc. Surg. 118, 569-570
   Full Text »    PDF »
Expression of Cyclooxygenase-2 mRNA After Global Ischemia Is Regulated by AMPA Receptors and Glucocorticoids • Editorial Comment.
J. Koistinaho, S. Koponen, P. H. Chan, and C. Y. Hsu (1999)
Stroke 30, 1900-1906
   Abstract »    Full Text »    PDF »
Regulation of GLUT-3 glucose transporter in the hippocampus of diabetic rats subjected to stress.
L. P. Reagan, A. M. Magarinos, L. R. Lucas, A. van Bueren, A. L. McCall, and B. S. McEwen (1999)
Am J Physiol Endocrinol Metab 276, E879-E886
   Abstract »    Full Text »    PDF »
Cytokines - killers in the brain?.
N. J Rothwell (1999)
J. Physiol. 514, 3-17
   Abstract »    Full Text »    PDF »
Three-Year Multicenter Surveillance of Pneumococcal Meningitis in Children: Clinical Characteristics, and Outcome Related to Penicillin Susceptibility and Dexamethasone Use.
M. Arditi, E. O. Mason Jr, J. S. Bradley, T. Q. Tan, W. J. Barson, G. E. Schutze, E. R. Wald, L. B. Givner, K. S. Kim, R. Yogev, et al. (1998)
Pediatrics 102, 1087-1097
   Abstract »    Full Text »
Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia.
M. Nakayama, K. Uchimura, R. L. Zhu, T. Nagayama, M. E. Rose, R. A. Stetler, P. C. Isakson, J. Chen, and S. H. Graham (1998)
PNAS 95, 10954-10959
   Abstract »    Full Text »    PDF »
Adrenal Steroid Regulation of Neurotrophic Factor Expression in the Rat Hippocampus.
H. M. Chao, R. R. Sakai, L. Y. Ma, and B. S. McEwen (1998)
Endocrinology 139, 3112-3118
   Abstract »    Full Text »    PDF »
Corticosteroid Regulation of Ion Channel Conductances and mRNA Levels in Individual Hippocampal CA1 Neurons.
S. M. Nair, T. R. Werkman, J. Craig, R. Finnell, M. Joels, and J. H. Eberwine (1998)
J. Neurosci. 18, 2685-2696
   Abstract »    Full Text »    PDF »
Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia.
K. J. Becker, R. M. McCarron, C. Ruetzler, O. Laban, E. Sternberg, K. C. Flanders, and J. M. Hallenbeck (1997)
PNAS 94, 10873-10878
   Abstract »    Full Text »    PDF »
Predictive Factors of Early Seizures After Acute Cerebrovascular Disease.
A. Arboix, L. Garcia-Eroles, J. B. Massons, M. Oliveres, and E. Comes (1997)
Stroke 28, 1590-1594
   Abstract »    Full Text »
Magnetic Resonance Imaging in the Congenital Adrenal Hyperplasia Population: Increased Frequency of White-Matter Abnormalities and Temporal Lobe Atrophy.
R. Nass, L. Heier, T. Moshang, S. Oberfield, A. George, M. I. New, and P. W. Speiser (1997)
J Child Neurol 12, 181-186
   Abstract »    PDF »
Glucocorticoids Enhance Oxidative Stress-Induced Cell Death in Hippocampal Neurons in Vitro.
C. Behl, F. Lezoualc'h, T. Trapp, M. Widmann, T. Skutella, and F. Holsboer (1997)
Endocrinology 138, 101-106
   Abstract »    Full Text »    PDF »
Use-Dependent Exaggeration of Neuronal Injury after Unilateral Sensorimotor Cortex Lesions.
D. A. Kozlowski, D. C. James, and T. Schallert (1996)
J. Neurosci. 16, 4776-4786
   Abstract »    Full Text »    PDF »
Pharmacologic Modulation of Recovery After Stroke: Clinical Data.
L. B. Goldstein (1991)
Neurorehabil Neural Repair 5, 129-140
   PDF »
Prednisone Effects on Neurochemistry and Behavior: Preliminary Findings.
O. M. Wolkowitz, D. Rubinow, A. R. Doran, A. Breier, W. H. Berrettini, M. A. Kling, and D. Pickar (1990)
Arch Gen Psychiatry 47, 963-968
   Abstract »    PDF »
Effect of neonatal handling on age-related impairments associated with the hippocampus.
M. Meaney, D. Aitken, C van Berkel, S Bhatnagar, and R. Sapolsky (1988)
Science 239, 766-768
   Abstract »    PDF »
Analytic Review: Ischemic Cerebrovascular Disease: Diagnosis and Management.
C. Tegeler and D. Sherman (1986)
J Intensive Care Med 1, 184-196
   Abstract »    PDF »
Social stress exacerbates stroke outcome by suppressing Bcl-2 expression.
A. C. DeVries, H.-D. Joh, O. Bernard, K. Hattori, P. D. Hurn, R. J. Traystman, and N. J. Alkayed (2001)
PNAS 98, 11824-11828
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)