Blood-brain barrier. Response

RESPONSE

We appreciate the interest that Drs. Hueng and Sytwu expressed in our recent report. To gain insight into features of the astrocytic component of the BBB in metastatic and primary brain tumors, we analyzed post-contrast MRI and compared that with the corresponding immunohistochemical and histological features of the astrocytic component of the neoplastic vasculature. We found that there was breakdown of the normal astrocyte–endothelial cell relationship of the BBB in areas of contrast extravasation on postcontrast MRI. Alternatively, in neoplastic regions without enhancement on postcontrast MRI, the normal physiological astrocyte-endothelial BBB relationship was maintained.

In their letter, Drs. Hueng and Sytwu indicate mannitol can be used to open the BBB and, if used, could affect the study results. To support their assertion, they cite a study by Palma and colleagues.³ Nevertheless, that study did not indicate that intravenous mannitol opened the BBB but rather demonstrated that “mannitol may leak through the altered BBB near gliomas” into adjacent white matter, which is consistent with the BBB disruption associated with contrast-enhancing gliomas examined in our study. Moreover, the same study found that there was minimal to no leakage of mannitol into the immediately surrounding white matter associated with meningiomas or metastases. The authors concluded that “in brain tissue surrounding extrinsic tumors like meningiomas and metastases, the BBB is largely normal or undisrupted, and edema builds up from leaking neoplastic vessels by bulk flow,” which is consistent with our study findings and previous analyses of neoplastic vascular permeability and edema.²

There are therapeutic situations in which mannitol can be used to purposely disrupt the BBB. Specifically, BBB disruption can occur when high doses of intraarterial (intracarotid or intravertebral artery) mannitol (200–300 ml) are given as a bolus over 30 seconds, which is performed in association with intraarterial chemotherapeutic delivery for treatment of intracranial neoplastic processes.^1,4 Consequently, while in specific circumstances mannitol delivered rapidly and intraarterially can open the BBB, we are confident that the findings of our study are consistent with previous data/findings and that intravenous infusions of perioperative mannitol would not impact the results.