Protection of the Blood–Brain Barrier as a Therapeutic Strategy for Brain Damage

Abstract

Severe brain damage by trauma, ischemia, and hemorrhage lead to fatal conditions including sudden death, subsequent complications of the extremities and cognitive dysfunctions. Despite the urgent need for treatments for these complications, currently available therapeutic drugs are limited. Blood-brain barrier (BBB) disruption is a common pathogenic feature in many types of brain damage. The characteristic pathophysiological conditions caused by BBB disruption are brain edema resulting from an excessive increase of brain water content, inflammatory damage caused by infiltrating immune cells, and hemorrhage caused by the breakdown of microvessel structures. Because these pathogenic features induced by BBB disruption cause fatal conditions, their improvement is a desirable strategy. Many studies using experimental animal models have focused on molecules involved in BBB disruption, including vascular endothelial growth factors (VEGFs), matrix metalloproteinases (MMPs) and endothelins (ETs). The inhibition of these factors in several experimental animals was protective against BBB disruption caused by several types of brain damage, and ameliorated brain edema, inflammatory damage, and hemorrhagic transformation. In patients with brain damage, the up-regulation of these factors was observed and was related to brain damage severity. Thus, BBB protection by targeting VEGFs, MMPs, and ETs might be a novel strategy for the treatment of brain damage.

Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes

“…AQP4, a critical component of an integrated water and potassium homeostasis ( Yukutake and Yasui, 2010 ), the expression has not changed after EA. Also, we found that EA stimulation at these parameters did not cause brain edema, which usually occurs after destruction of the BBB ( Michinaga and Koyama, 2017 ). Neuroglia, especially microglia and astrocytes, provide dynamicity to the brain.…”

Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic stroke models

“…Of note, brain endothelial cells are the main component of the NVU. Compromise of the NVU during ischemia results in BBB disruption and the influx of inflammatory cells and substances from the systemic circulation which amplifies brain injury [34]. The elucidation the molecular mechanisms underlying ischemic BBB damage is pivotal to understand NVU impairment during ischemia.…”

Pengaruh Pemberian Ekstrak Etanol Rimpang Lengkuas (Alpinia Galanga) Terhadap Gambaran Histopatologi Otak Mencit (Mus Musculus L) Yang Diinduksi Monosodium Glutamate

“…Kerapatan pada sel-sel endotel sawar darah otak didukung oleh adanya Tight Junction (TJ) yang terdiri atas beberapa protein, yaitu claudin-5 (CLN-5), occludin, dan Zonula occludens-1 (ZO-1). [17] Tight Junction merupakan pertahanan pertama yang dimiliki oleh sawar darah otak. Nantinya TJ akan menghambat gerakan seluruh molekul, kecuali molekul yang mampu melewati membran sel dengan kelarutannya dalam lemak (contohnya oksigen, karbon dioksida, etanol, dan hormon-hormon steroid) dan yang dapat melewati sistem transpor spesifik (contohnya glukosa dan asam amino).…”