Engineering strategies towards overcoming bleeding and glial scar formation around neural probes

Neural probes are sophisticated electrophysiological tools used for intra-cortical recording and stimulation. These microelectrode arrays, designed to penetrate and interface the brain from within, contribute at the forefront of basic and clinical neuroscience. However, one of the challenges and currently most significant limitations is their ‘seamless’ long-term integration into the surrounding brain tissue. Following implantation, which is typically accompanied by bleeding, the tissue responds with a scarring process, resulting in a gliotic region closest to the probe. This glial scarring is often associated with neuroinflammation, neurodegeneration, and a leaky blood–brain interface (BBI). The engineering progress on minimizing this reaction in the form of improved materials, microfabrication, and surgical techniques is summarized in this review. As research over the past decade has progressed towards a more detailed understanding of the nature of this biological response, it is time to pose the question: Are penetrating probes completely free from glial scarring at all possible?

Lactate-induced effects on bovine granulosa cells are mediated via PKA signaling

Abstractl-lactate acts as a signaling molecule in bovine granulosa cells (GCs). The initiated alterations depend on the transport of l-lactate into the cells via monocarboxylate transporters. In the present study, we further elucidated the intracellular actions of l-lactate and tested whether the PKA signaling pathway is involved. Therefore, we treated cultured bovine GCs with l-lactate and PKA inhibitors H-89 and KT5720, and with an activator of PKA, 6-Bnz-cAMP. l-lactate treatment resulted in decreased estradiol production and downregulation of CYP19A1, FSHR, and LHCGR as well as in the upregulation of the markers of early luteinization PTX3, RGS2, and VNN2. These specific l-lactate effects were almost completely abolished by pre-treatment of the GCs with both inhibitors of PKA signaling. In addition, also the l-lactate-induced upregulation of LDHA and of the monocarboxylate transporters SLC16A1 and SLC16A7 was abolished after PKA inhibition. An activation of the PKA with 6-Bnz-cAMP revealed similar effects on the gene expression like l-lactate alone. In summary, the presented data demonstrate that l-lactate-induced effects on GCs are mediated via PKA signaling thus supporting the role of l-lactate as signaling molecule during the folliculo-luteal transition.