Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels.

OBJECTIVE: Biocompatibility is a major issue for chronic neural implants, involving inflammatory and wound healing responses of neurons and glial cells. To enhance biocompatibility, we developed silicon-parylene hybrid neural probes with open architecture electrodes, microfluidic channels and a reservoir for drug delivery to suppress tissue responses. APPROACH: We chronically implanted our neural probes in the rat auditory cortex and investigated (1) whether open architecture electrode reduces inflammatory reaction by measuring glial responses; and (2) whether delivery of antibiotic minocycline reduces inflammatory and tissue reaction. Four weeks after implantation, immunostaining for glial fibrillary acid protein (astrocyte marker) and ionizing calcium-binding adaptor molecule 1 (macrophages/microglia cell marker) were conducted to identify immunoreactive astrocyte and microglial cells, and to determine the extent of astrocytes and microglial cell reaction/activation. A comparison was made between using traditional solid-surface electrodes and newly-designed electrodes with open architecture, as well as between deliveries of minocycline and artificial cerebral-spinal fluid diffused through microfluidic channels. MAIN RESULTS: The new probes with integrated micro-structures induced minimal tissue reaction compared to traditional electrodes at 4 weeks after implantation. Microcycline delivered through integrated microfluidic channels reduced tissue response as indicated by decreased microglial reaction around the neural probes implanted. SIGNIFICANCE: The new design will help enhance the long-term stability of the implantable devices.

Extent of nerve cell injury in Marmarou's model compared to other brain trauma models.

OBJECTIVES: We sought to determine the extent of nerve cell injury in the Marmarou's acceleration impact model of diffuse brain injury. METHODS: Sensitive markers for cell injury including immunostaining for beta-amyloid precursor protein (beta-APP, a marker for diffuse axonal injury, DAI), Fluoro-Jade (FJ) histochemistry and electron microscopy (EM) were used in sham-operated and traumatized brains. RESULTS: APP immunostaining confirmed and extended previous findings of DAI in association and subcortical fiber systems in the white matter after injury. Increasing FJ labeling of neurons in layers II-III of sensorimotor cortex (smCx) from 4 to 48 hours after trauma and scattered labeled cells were found in the lower cortical layers. EM confirmed the presence of dystrophic pyramidal neurons in layers II-III of smCx 24 and 48 hours post-trauma. DISCUSSION: Taken together, the data revealed significant nerve cell injury without apparent cell death in this model.

Behavioral pre-conditioning enhances angiogenesis and cognitive outcome after brain trauma.

OBJECTIVES: In this study, we used Marmarou's model of traumatic brain injury (TBI) and sought to determine: (1) the effect of TBI on cognitive outcome measured on a radial arm maze; (2) the effect of behavioral conditioning before TBI, i.e. pre-conditioning, on cognitive outcome; (3) the effect of pre-conditioning on angiogenesis. METHODS: Cognitive outcome was measured by performance on an eight-arm radial maze. Behavioral conditioning consisted of daily exposure of animals to the radial arm maze. Latency and number of errors were recorded as an index of overall performance and acquisition of the test. Extent of angiogenesis was measured by vascular endothelial growth factor receptor 2 (VEGFR2) immunofluorescence and by determining capillary density. RESULTS: Our results indicated that trauma alone causes significant cognitive impairments. Pre-conditioning caused a marked improvement in radial arm maze performance following injury. These results coincide with both a significant increase in VEGFR2 expression and increased capillary density within the cortex and hippocampus. DISCUSSION: TBI causes significant impairments in cognition. These deficits can be ameliorated using a pre-conditioning paradigm. While the precise mechanism has yet to be elucidated, our results indicate that angiogenesis may underlie the cognitive sparing seen in pre-conditioned animals.