Intracarotid injection of hyperosmolar mannitol produced a larger infarct than normal saline during the first few hours of distal middle cerebral artery occlusion with a smaller regional plasma volume.

BACKGROUND

Although hyperosmolar mannitol has been used clinically to reduce intracranial pressure, its use in acute ischemic stroke remains controversial. We investigated whether other characteristics of hyperosmolar mannitol such as its effects on cerebral regional plasma volume or blood-brain barrier permeability would affect infarct size when intracranial pressure is zero during the early ischemic stroke.

METHODS

One hour after a distal middle cerebral artery occlusion with craniotomy which results in essentially zero intracranial pressure, the rats were treated with 25 % mannitol or normal saline via the ipsilateral external carotid artery. Control rats received no treatment. Two hours after middle cerebral artery occlusion, infarct size along with the blood-brain transfer coefficient of 14C-α-aminoisobutyric acid, and the volume of 3H-dextran distribution were measured to assess blood-brain barrier permeability and plasma volume respectively.

RESULTS

At one hour after intracarotid artery injection and two hours after middle cerebral artery occlusion, hyperosmolar mannitol treatment significantly reduced cerebral regional plasma volume in the ischemic cortex (3.0 mL/100 g ± 1.6) compared to normal saline (6.1 mL/100 g ± 1.3, p < 0.0001) or no treatment (4.8 mL/100 g ± 1.2, p < 0.05). Blood-brain barrier permeability was similar regardless of treatments in the ischemic cortex. The percentage of cortical infarcted area relative to total cortical area was significantly higher in the mannitol-treated rats (14.0 % ± 4.5) compared to normal saline treatment (6.6 % ± 1.4, p < 0.01).

CONCLUSIONS

Our findings suggest that when intracranial pressure effect is excluded, hyperosmolar mannitol may exacerbate neuronal damage in the very early stages of acute ischemic stroke, and that cerebral regional plasma volume plays an important role in neuronal survival.