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Biomaterials. 2014 Dec;35(36):9620-34. doi: 10.1016/j.biomaterials.2014.08.006. Epub 2014 Aug 28.

Effects of caspase-1 knockout on chronic neural recording quality and longevity: insight into cellular and molecular mechanisms of the reactive tissue response.

Author information

1
Bioengineering, University of Pittsburgh, USA; Center for Neural Basis of Cognition, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA. Electronic address: tdk18@pitt.edu.
2
Bioengineering, University of Pittsburgh, USA.
3
Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, USA.
4
Bioengineering, University of Pittsburgh, USA; Center for Neural Basis of Cognition, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA. Electronic address: xic11@pitt.edu.

Abstract

Chronic implantation of microelectrodes into the cortex has been shown to lead to inflammatory gliosis and neuronal loss in the microenvironment immediately surrounding the probe, a hypothesized cause of neural recording failure. Caspase-1 (aka Interleukin 1β converting enzyme) is known to play a key role in both inflammation and programmed cell death, particularly in stroke and neurodegenerative diseases. Caspase-1 knockout (KO) mice are resistant to apoptosis and these mice have preserved neurologic function by reducing ischemia-induced brain injury in stroke models. Local ischemic injury can occur following neural probe insertion and thus in this study we investigated the hypothesis that caspase-1 KO mice would have less ischemic injury surrounding the neural probe. In this study, caspase-1 KO mice were implanted with chronic single shank 3 mm Michigan probes into V1m cortex. Electrophysiology recording showed significantly improved single-unit recording performance (yield and signal to noise ratio) of caspase-1 KO mice compared to wild type C57B6 (WT) mice over the course of up to 6 months for the majority of the depth. The higher yield is supported by the improved neuronal survival in the caspase-1 KO mice. Impedance fluctuates over time but appears to be steadier in the caspase-1 KO especially at longer time points, suggesting milder glia scarring. These findings show that caspase-1 is a promising target for pharmacologic interventions.

KEYWORDS:

Blood-brain barrier; Foreign Body Response; Impedance; Mechanical tissue strain; Oligodendrocytes; Pericyte

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