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(Stroke. 1997;28:1351-1356.)
© 1997 American Heart Association, Inc.

Articles

Impaired Calcium Regulation in Subcortical Vascular Encephalopathy

Anne Eckert, PhD; Manfred Oster, MD; Hans Förstl, MD; Michael Hennerici, MD; Walter E. Müller, PhD

From the Departments of Psychopharmacology (A.E., W.E.M.) and Psychiatry (H.F.), Central Institute of Mental Health, and the Department of Neurology (M.O., M.H.), Klinikum Mannheim of the University of Heidelberg, Mannheim, Germany.

Correspondence to Prof Dr Walter E. Müller, Department of Pharmacology, University of Frankfurt, Biocenter, Geb N260, D-60439 Frankfurt, Germany. E-mail psymail{at}as200.zimannheim.de

Background and Purpose A number of clinical observations and first in vitro findings indicate that chronic cerebral ischemia influences immunologic status, such as the proliferative response of T lymphocytes. The purpose of the present report was to assess (1) whether changes of immune function are likewise detectable in patients with progressive subcortical vascular encephalopathy (SVE) by investigating the [Ca²⁺]_i homeostasis of lymphocytes and (2) whether differences exist in calcium regulation between lymphocytes from SVE patients and from Alzheimer's disease (AD) patients. This is of great interest, since specific changes have been reported recently in AD patients.

Methods [Ca²⁺]_i was recorded in 26 patients with SVE, 26 age-matched nondemented control subjects, and 26 age-matched patients with AD. Basal [Ca²⁺]_i and [Ca²⁺]_i after lymphocyte activation with the mitogen phytohemagglutinin (PHA) were measured with the fura 2 method. In addition, modulation of the Ca²⁺ signaling by the peptide ß-amyloid and the potassium channel blocker tetraethylammonium was studied.

Results Basal [Ca²⁺]_i was not different between patients and control subjects. After stimulation with PHA, however, a significant reduction of the Ca²⁺ response could be observed in lymphocytes of SVE patients compared with control subjects and with AD patients, providing evidence that the Ca²⁺ homeostasis of lymphocytes is impaired in SVE. The effect of the peptide ß-amyloid, the major constituent of senile plaques in AD brain, on Ca²⁺ signaling was similar in SVE patients and nondemented control subjects but typically reduced in cells of AD patients. Potassium channels were not involved in the impaired Ca²⁺ response of SVE lymphocytes after cell activation.

Conclusions [Ca²⁺]_i is not only one of the most important second messengers in signal transduction of many cells but also an early event in the signal cascade of cell proliferation as a reaction to antigen recognition. This mechanism seems to be impaired in SVE. These findings may result in new insights regarding the pathogenesis of this disease and the possible involvement of inflammatory or immunologic disturbances.

Key Words: calcium • cerebrovascular disorders • dementia • lymphocytes • encephalopathy

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