E. Tasdemiroglu et al., EFFECTS OF ANTIOXIDANTS ON THE BLOOD-BRAIN-BARRIER AND POSTISCHEMIC HYPEREMIA, Acta neurochirurgica, 131(3-4), 1994, pp. 302-309
The role of free oxygen radicals in blood-brain barrier (BBB) disrupti
on and postischemic hyperemia was evaluated in the rabbit model of foc
al cerebral ischemia-reperfusion. Six groups of rabbits underwent clip
ping of the anterior cerebral, middle cerebral, and intracranial inter
nal carotid arteries. Cerebral blood flow (CBF) was measured by using
radiolabeled microspheres, before, during, and 15 minutes after 1-hour
occlusion of these arteries. After 50 minutes of ischemia, Group 1 an
imals (control) received a placebo. Animals in Groups 2-4 received one
of three drugs: catalase at 10 mg/kg, methimazole at 5 mg/kg, or indo
methacin at 10 mg/kg. A fifth group received a tungsten-supplemented d
iet for 14 days before ischemia was induced, and a sixth group was sha
m operated. Microvascular integrity within the brain was determined by
the presence or absence of Evan's Blue (EB)-albumin dye leakage acros
s the BBB and was measured by microspectrofluorometry. In the control
group during ischemia, CBF dropped to 14%, 7%, and 11% of preischemic
levels in rostral, middle, and caudal sections of the brain, respectiv
ely, as characterized by extensive EB-albumin dye leakage through the
BBB into the ischemic hemisphere. During early reperfusion, postischem
ic hyperemia was associated with an increase in CBF of 128%, 123%, and
129% of control in the rostral, middle, and caudal sections of the br
ain, respectively. In all treated groups and in the group receiving a
tungsten-supplemented diet, BBB integrity was protected during reperfu
sion without inhibition of postischemic hyperemia. This study suggests
that early disruption of the BBB to large molecules is mediated by fr
ee oxygen radicals, which inhibit rather than cause postischemic hyper
emia.