The pineal hormone melatonin is a highly efficient physiological scavenger
of free radicals involved in secondary brain damage. A variety of experimen
tal studies have demonstrated a neuroprotective effect for melatonin, based
on its antioxidant activity. The purpose of the present study was to inves
tigate the time-dependency and a possible protective effect of exogenous me
latonin in the cortical impact model in rats. The protective effect was qua
ntified determining contusion volume, brain edema and brain water content.
45 anesthetized male Sprague-Dawley rats (250-350 mg) were subjected to cor
tical impact injury of moderate severity (7 mis, deformation 2 mm). Melaton
in (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, imm
ediately after, and 1 and 2 hours after trauma during daytime and nighttime
. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric
swelling, brain water content, cerebral perfusion pressure and intracrania
l pressure 24 hours after injury were investigated.
Melatonin, given during nighttime, significantly reduced contusion volume c
orresponding to a mean reduction of contusion volume of 27% (placebo, n = 7
: 41.9 +/- 5.2 mm(3), melatonin, n = 8: 30.5 +/- 4.2 mm(3), p < 0.05). Give
n during daytime, the reduction in contusion volume was not significant (pl
acebo, n = 8: 42.1 <plus/minus> 5.1 mm(3), melatonin, n = 8: 35.9 +/- 2.2 m
m(3), reduction of 15%, p = 0.08, n.s.). Hemispheric swelling was unchanged
by melatonin treatment. Mean arterial blood pressure and rectal temperatur
e remained stable before and after the cortical impact injury and injection
of melatonin. This study shows that melatonin significantly reduces contus
ion volume with major effects during night.