Spatiotemporal Distribution of Agrin after Intrathecal Injection and Its Protective Role in Cerebral Ischemia/Reperfusion Injury

Abstract

Intrathecal injection, drugs transporting along perivascular spaces, represents an important route for maintaining blood–brain barrier (BBB) integrity after cerebral ischemia/reperfusion (I/R) injury. However, after being directly injected into cerebrospinal fluid (CSF), the temporal and spatial changes in the distribution of therapeutic protein drugs have remained unknown. Here, with positron emission tomography (PET) imaging, the uptake of 89Zr‐agrin is noninvasively and dynamically monitored. These data demonstrate the time–activity curve of drugs in the brain subregions and their spatial distribution in different organs after intrathecal administration. Furthermore, agrin treatment effectively inhibits BBB disruption by reducing the loss of tight‐junctional proteins. Importantly, the infarct volume is reduced; the number of apoptotic neurons is decreased; and neurological function is improved in mouse I/R injury models. Thus, intrathecal injection of agrin provides the basis for a new strategy to research and develop protein drugs for reducing the aggravation of I/R injury.

A Blood‐Responsive AIE Bioprobe for the Ultrasensitive Detection and Assessment of Subarachnoid Hemorrhage

“…[42][43][44] Unfortunately, this method was unable to identify bleeding in mice that had already developed SAH. Intrathecal injection of TTVP may be a way of compensating this defect, and represents an important direction for subsequent optimization research; [45,46] it also provides new inspiration for further applications of the TTVP bleedingindicator probe, which may be extended to various internal hemorrhage models with a closed internal environment using different delivery methods.…”

Bioactive Nanoenzyme Reverses Oxidative Damage and Endoplasmic Reticulum Stress in Neurons under Ischemic Stroke

“…To solve the problem of brain damage caused by ischemia-reperfusion and clinical applications, growing attention has been given to unitary and multifunctional nanomaterials, especially those with enzyme-mimetic capacities with scavenging ROS. − Significantly, Mn 3 O 4 nanomaterials are relatively small in size and have excellent biomimetic activity. , Therefore, we have prioritized the selection of Mn 3 O 4 nanomaterials having smaller size and better antioxidant enzyme-mimetic capacity for scavenging ROS during ischemia and reperfusion. Mn 3 O 4 is an inorganic nanomaterial containing the element manganese, which can release manganese ions in circulation, promote the activity of superoxide dismutase 2 (SOD2) in the body, and participate in short- and long-term protection strategies .…”