Summary: The protection of the brain from blood‐borne toxins, proteins, and cells is critical to the brain’s normal function. Accordingly, a compromise in the blood–brain barrier (BBB) function accompanies many neurologic disorders, and is tightly associated with brain inflammatory processes initiated by both infiltrating leukocytes from the blood, and activation of glial cells. Those inflammatory processes contribute to determining the severity and prognosis of numerous neurologic disorders, and can both cause, and result from BBB dysfunction. In this review we examine the role of BBB and inflammatory responses, in particular activation of transforming grown factor β (TGFβ) signaling, in epilepsy, stroke, and Parkinson’s disease.

Brain damage due to stroke or traumatic brain injury (TBI), both leading causes of serious long-term disability, often leads to the development of epilepsy. Patients who develop post-injury epilepsy tend to have poor functional outcomes. Emerging evidence highlights a potential role for blood-brain barrier (BBB) dysfunction in the development of post-injury epilepsy. However, common mechanisms underlying the pathological hyperexcitability are largely unknown. Here, we show that comparative transcriptome analyses predict remodeling of extracellular matrix (ECM) as a common response to different types of injuries. ECM-related transcriptional changes were induced by the serum protein albumin via TGFβ signaling in primary astrocytes. In accordance with transcriptional responses, we found persistent degradation of protective ECM structures called perineuronal nets (PNNs) around fast-spiking inhibitory interneurons, in a rat model of TBI as well as in brains of human epileptic patients. Exposure of a naïve brain to albumin was sufficient to induce the transcriptional and translational upregulation of molecules related to ECM remodeling and the persistent breakdown of PNNs around fast-spiking inhibitory interneurons, which was contingent on TGFβ signaling activation. Our findings provide insights on how albumin extravasation that occurs upon BBB dysfunction in various brain injuries can predispose neural circuitry to the development of chronic inhibition deficits.

Recently, three-dimensional printing (3DP) technology has been widely adopted in biology and biomedical applications, thanks to its capacity to readily construct complex 3D features. Using hot-melt extrusion 3DP, scaffolds for bone tissue engineering were fabricated using a composite of biodegradable polycaprolactone (PCL) and hydroxyapatite (HA). However, there are hardly any published reports on the application of the fused deposition modeling (FDM) method using feed filaments, which is the most common 3D printing method. In this study, we report on the fabrication and characterization of biocompatible filaments made of polycaprolactone (PCL)/hydroxyapatite (HA), a raw material mainly used for bone scaffolds, using FDM 3D printing. A series of filaments with varying HA content, from 5 to 25 wt.%, were fabricated. The mechanical and electrical properties of the various structures, printed using a commercially available 3D printer, were examined. Specifically, mechanical tensile tests were performed on the 3D-printed filaments and specimens. In addition, the electrical dielectric properties of the 3D-printed structures were investigated. Our method facilitates the fabrication of biocompatible structures using FDM-type 3DP, creating not only bone scaffolds but also testbeds for mimicking bone structure that may be useful in various fields of study.

The process of brain remodeling after stroke is time- and neural activity-dependent, and the latter makes it inherently sensitive to behavioral experiences. This generally supports targeting early dynamic periods of post-stroke neural remodeling with rehabilitative training (RT). However, the specific neural events that optimize RT effects are unclear and, as such, cannot be precisely targeted. Here we review evidence for, potential mechanisms of, and ongoing knowledge gaps surrounding time-sensitivities in RT efficacy, with a focus on findings from animal models of upper extremity RT. The reorganization of neural connectivity after stroke is a complex multiphasic process interacting with glial and vascular changes. Behavioral manipulations can impact numerous elements of this process to affect function. RT efficacy varies both with onset time and its timing relative to the development of compensatory strategies with the less-affected (nonparetic) hand. Earlier RT may not only capitalize on a dynamic period of brain remodeling but also counter a tendency for compensatory strategies to stamp-in suboptimal reorganization patterns. However, there is considerable variability across injuries and individuals in brain remodeling responses, and some early behavioral manipulations worsen function. The optimal timing of RT may remain unpredictable without clarification of the cellular events underlying time-sensitivities in its effects.