title: Effects of caspase-1 knockout on chronic neural recording quality and longevity: insight into cellular and molecular mechanisms of the reactive tissue response.
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.
authors.affiliation: 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.
authors.forename: Takashi D Y
authors.initials: TD
authors.lastname: Kozai
authors.affiliation: Bioengineering, University of Pittsburgh, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, USA.
authors.forename: Lance M
authors.initials: LM
authors.lastname: Bodily
authors.affiliation: Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Caparosa
authors.affiliation: Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, USA.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Zenonos
authors.affiliation: Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, USA.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Carlisle
authors.affiliation: Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Friedlander
authors.affiliation: 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.
authors.forename: X Tracy
authors.initials: XT
authors.lastname: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics*; D005549:Foreign-Body Reaction / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058117:Neural Prostheses / Q000009:adverse effects*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology
chemical_list: D020170:Caspase 1
keywords: Blood-brain barrier; Foreign Body Response; Impedance; Mechanical tissue strain; Oligodendrocytes; Pericyte