Background and Purpose: The aim of this study was to investigate the neurobehavioral consequences of focal ischemia in rats.Methods: We induced permanent occlusion of the left middle cerebral artery in 14 SpragueDawley rats, and used 13 sham-operated rats as controls. During surgery, brain temperature and body temperature were kept at normothermia. Neurobehavioral studies (neurological examination, passive avoidance task, Y maze test, and modified open-field test) were carried out 4 days after ischemia before killing the rats to evaluate histological damage.Results: Ischemia induced large infarcts in the cortex (138.6±8.5 mm

The pineal hormone melatonin has recently been shown to exert neuroprotective activity in a variety of experimental neuropathologies in which free radicals are involved. This neuroprotective effect has been attributed to the antioxidant properties of melatonin. Considering that free radicals also play a deleterious role in traumatic brain injury (TBI), the purpose of the present study was to determine whether melatonin would have a beneficial effect in this pathology. Head injury was induced in mice and the neurological deficit was evaluated at 24 hr by a grip test. In this model, the free radical scavenger, alpha-phenyl-tert-butyl-nitrone (2 x 100 mg/kg, i.p.) given 5 min and repeated at 4 hr after TBI was neuroprotective. Melatonin (1.25 mg/kg, i.p.) given 5 min and repeated at 1, 2, and 3 hr after head trauma also significantly reduced the neurological deficit. This beneficial effect was not due to melatonin-induced hypothermia since repeated treatment with melatonin did not modify the colonic temperature of mice. This study shows that melatonin exerts a beneficial effect on the neurological deficit induced by traumatic brain injury in mice. The mechanisms of this neuroprotection remains to be established, and more particularly, the contribution of the antioxidant activity of melatonin.

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1 The temporal changes in constitutive NO-synthase (cNOS) and in calcium-independent NO-synthase activities were studied in mice subjected to 2 h of transient focal cerebral ischaemia. The changes in brain nitrites/nitrates (NO x ) content were also studied. 2 NOS activities were measured by the conversion of L-[ 14 C]-arginine to L-[ 14 C]-citrulline. Brain NO x contents were investigated by the Griess colourimetric method. 3 cNOS activity in the infarcted cortical area was signi®cantly reduced after 6 h of reperfusion and this activity remained attenuated for up to 10 days after ischaemia. A calcium-independent NOS activity began to increase 48 h after reperfusion, reached a maximum at 7 days and returned to baseline at 10 days. 4 There was a signi®cant increase of brain NO x content beginning after 3 days of reperfusion. This increase was maximal at 7 days and returned to baseline at 10 days. 5 Thus, ischaemia followed by recirculation leads to a rapid, prolonged drop in cNOS activity in the infarcted cortex. There is also a substantial appearance of calcium-independent NOS activity in the later phase of transient ischaemia, leading to an important increase of NO x production.