Borneol Attenuates Ultrasound-Targeted Microbubble Destruction-Induced Blood-Brain Barrier Opening in Focal Cerebral Ischemia.

Ultrasound-targeted microbubble destruction (UTMD) and the herb medicine borneol can both facilitate the delivery of therapeutic agents to diseased brain regions and serve as promising adjuvant neuroprotective therapies. Our preliminary experiments showed that UTMD could exacerbate ischemic blood-brain barrier (BBB) opening, while borneol can protect the BBB. In this study, we tested the hypothesis that the combination of UTMD and borneol could attenuate UTMD-induced injury to the BBB under ischemic stroke conditions. Male albino mice were subjected to 60-min middle cerebral artery occlusion (MCAO) with reperfusion. Borneol and UTMD was given to mice 3 days before and 24 h after MCAO induction. BBB permeability, brain water contents, ultrastructural changes of the BBB and histopathological alterations were evaluated. Our data demonstrated that UTMD aggravated the leakage of Evans blue dye, ultrastructural alterations of cerebral microvasculature, brain edema, and even induced cerebral hemorrhage in ischemic stroke mice. Pretreatment with borneol significantly attenuated the above detrimental effects of UTMD on the BBB. This study indicates that under ischemic stroke conditions, the BBB becomes vulnerable to UTMD intervention, and the combination of borneol can help to maintain the integrity of the BBB.

Additive Neuroprotective Effect of Borneol with Mesenchymal Stem Cells on Ischemic Stroke in Mice.

Intravenous stem cell transplantation initiates neuroprotection related to the secretion of trophic factor. Borneol, a potential herbal neuroprotective agent, is a penetration enhancer. Here, we aimed to investigate whether they have additive neuroprotective effect on cerebral ischemia. Borneol was given to mice by gavage 3 days before middle cerebral artery occlusion (MCAO) induction until the day when the mice were sacrificed. Mesenchymal stem cells (MSCs) were intravenously injected at 24 h after MCAO induction. Neurological deficits, infarct volume, cell death, and neurogenesis were evaluated. Combined use of MSCs and borneol could more effectively reduce infarction volume and cell apoptosis, enhance neurogenesis, and improve the functional recovery than that of MSCs alone. The findings showed that combined use of borneol and stem cells provided additive neuroprotective effect on cerebral ischemia. However, the supposed effect of borneol on the improved MSC penetration still needs further direct evidence.