Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Address for correspondence: Russel J. Reiter, Ph.D., Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Voice: 210-567-3859; fax: 210-567-6948.
reiter{at}uthscsa.edu
Ann. N.Y. Acad. Sci. 993: 35-47 (2003).
This review summarizes the numerous reports that have documented
the neuroprotective actions of melatonin in experimental models
of ischemia/reperfusion injury (stroke). In these investigations,
which have used three species (rat, gerbil, and cat), melatonin
was universally found to reduce brain damage that normally occurs
as a consequence of the temporary interruption of blood flow
followed by the reflow of oxygenated blood to the brain. The
exogenous administration of melatonin in these experimental
stroke models reduced infarct volume, lowered the frequency
of apoptosis, increased the number of surviving neurons, reduced
reactive gliosis, lowered the oxidation of neural lipids and
oxidatively damaged DNA, induced
bcl-2 gene expression (the
activity of which improves cell survival), upregulated excision
repair cross-complementing factor 6 (an essential gene for preferential
DNA excision repair), restrained poly(ADP ribose) synthetase
(which depletes cellular NAD resulting in the loss of ATP) activity,
and improved neurophysiologic outcomes. Under no circumstances
did melatonin exacerbate the damage associated with ischemia/reperfusion
injury. As well as the beneficial pharmacologic actions of melatonin,
several studies show that a relative deficiency of endogenous
melatonin exaggerates neural damage due to stroke; this suggests
that even physiologic concentrations of melatonin normally serve
to protect the brain against damage. The primary action to explain
melatonin's protective effects may relate to its ubiquitous
direct and indirect antioxidative actions, although other beneficial
functions of melatonin are not precluded.
