Curtin Health Innovation Research Institute, Curtin University, WA, Australia; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, WA, Australia.
Curtin Health Innovation Research Institute, Curtin University, WA, Australia; School of Public Health, Faculty of Health Sciences, Curtin University, WA, Australia.
Pharmacol Res. 2019 Mar;141:291-297. doi: 10.1016/j.phrs.2019.01.009. Epub 2019 Jan 4.
Type-2 diabetes (T2D) increases the risk of dementia by ˜5-fold, however the mechanisms by which T2D increases dementia risk remain unclear. Evidence suggests that the heightened inflammation and oxidative stress in T2D may lead to disruption of the blood-brain barrier (BBB), which precedes premature cognitive decline. Studies show that vascular-targeted anti-inflammatory treatments protect the BBB by attenuating neuroinflammation, and in some studies attenuate cognitive decline. Yet, this potential pathway is understudied in T2D-associated cognitive impairment. In recent years, therapeutic potential of cannabinoids has gained much interest. The two major cannabinoids, cannabidiol and tetrahydrocannabinol, exert anti-inflammatory and vascular protective effects, however few studies report their potential for reversing BBB dysfunction, particularly in T2D. Therefore, in this review, we summarize the current findings on the role of BBB dysfunction in T2D-associated dementia and consider the potential therapeutic use of cannabinoids as a protectant of cerebrovascular BBB protection.
2 型糖尿病（T2D）使痴呆的风险增加约 5 倍，然而，T2D 增加痴呆风险的机制仍不清楚。有证据表明，T2D 中炎症和氧化应激的加剧可能导致血脑屏障（BBB）的破坏，这先于认知能力的过早下降。研究表明，血管靶向抗炎治疗通过减轻神经炎症来保护 BBB，并且在一些研究中可以减轻认知能力下降。然而，在与 T2D 相关的认知障碍中，这种潜在途径的研究还不够充分。近年来，大麻素的治疗潜力引起了广泛关注。两种主要的大麻素，大麻二酚和四氢大麻酚，具有抗炎和血管保护作用，但是很少有研究报告它们在逆转 BBB 功能障碍方面的潜力，特别是在 T2D 中。因此，在本综述中，我们总结了 BBB 功能障碍在与 T2D 相关的痴呆中的作用的现有发现，并考虑了大麻素作为脑血管 BBB 保护的保护剂的潜在治疗用途。
