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Published on: August 18, 2018
Systemically administered platelet-inspired nanoparticles to reduce inflammation surrounding intracortical
Longshun Li1, Dhariyat M Menendez-Lustri1, Aniya Hartzler2
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, United States.
Platelet-inspired nanoparticles (PINs) reduce neuroinflammation around neural implants by targeting injury sites and sealing the blood-brain barrier. Repeated dosing of PINs shows promise for improving neural recording quality.
Area of Science:
- Biomaterials Science
- Neuroscience
- Nanotechnology
Background:
- Intracortical microelectrodes (IMEs) are crucial for neural signal acquisition in neuroscience and brain-machine interfaces (BMIs).
- Neuroinflammation, triggered by vascular damage during IME insertion, compromises signal quality.
- Platelet-inspired nanoparticles (PINs) are designed to target injuries and mimic platelet functions.
Purpose of the Study:
- To investigate the potential of systemically administered PINs to mitigate neuroinflammation at IME implant sites.
- To assess the biodistribution and efficacy of PINs in reducing blood-brain barrier (BBB) permeability and neuroinflammation.
- To evaluate the long-term effects of repeated PIN dosing on neural implant sites.
Main Methods:
- Male Sprague Dawley rats received IME implantations followed by single or weekly doses of Cy5-labeled PINs.
- Biodistribution was analyzed using in vivo live imaging (IVIS).
- Neuroinflammation, BBB permeability, and platelet activation were assessed via immunohistochemistry (IHC) at various time points.
Main Results:
- PINs accumulated at IME interfaces acutely (0-4 days post-implantation) and after 4 weeks of repeated dosing.
- Peak levels of activated platelets, microglia/macrophages (CD68), and PINs were observed at 3 days post-implantation.
- Compared to controls, the PINs group showed reduced CD68 and IgG levels, indicating decreased neuroinflammation and BBB leakage after 4 weeks.
Conclusions:
- PINs effectively target IME-tissue interfaces and co-localize with activated platelets.
- PIN administration reduces neuroinflammatory markers and BBB leakage.
- Repeated dosing of PINs is a promising strategy for enhancing neural recording quality by mitigating implant-induced neuroinflammation.
