Objective. Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication. In vitro and in vivo studies have demonstrated the seizure-suppressing effect of local cooling in various animal models. In our work, focal brain cooling in a bicuculline induced epilepsy model in rats is demonstrated and evaluated using a multimodal micro-electrocorticography (microECoG) device.Approach. We designed and experimentally tested a novel polyimide-based sensor array capable of recording microECoG and temperature signals concurrently from the cortical surface of rats.The effect of cortical cooling after seizure onset was evaluated using 32 electrophysiological sites and 8 temperature sensing elements covering the brain hemisphere, where injection of the epileptic drug was performed. The focal cooling of the cortex right above the injection site was accomplished using a miniaturized Peltier chip combined with a heat pipe to transfer heat. Control of cooling and collection of sensor data was provided by a custom designed Arduino based electronic board. We tested the experimental setup using an agar gel model in vitro, and then in vivo in Wistar rats.Main results. Spatial variation of temperature during the Peltier controlled cooling was evaluated through calibrated, on-chip platinum temperature sensors. We found that frequency of epileptic discharges was not substantially reduced by cooling the cortical surface to 30 °C, but was suppressed efficiently at temperature values around 20 °C. The multimodal array revealed that seizure-like ictal events far from the focus and not exposed to high drop in temperature can be also inhibited at an extent like the directly cooled area.Significance. Our results imply that not only the absolute drop in temperature determines the efficacy of seizure suppression, and distant cortical areas not directly cooled can be influenced.

The long-term application of central nervous system implants is currently limited by the negative response of the brain tissue, affecting both the performance of the device and the survival of nearby cells. Topographical modification of implant surfaces mimicking the structure and dimensions of the extracellular matrix may provide a solution to this negative tissue response and has been shown to affect the attachment and behavior of both neurons and astrocytes. In our study, commonly used neural implant materials, silicon, and platinum were tested with or without nanoscale surface modifications. No biological coatings were used in order to only examine the effect of the nanostructuring.We seeded primary mouse astrocytes and hippocampal neurons onto four different surfaces: flat polysilicon, nanostructured polysilicon, and platinum-coated versions of these surfaces. Fluorescent wide-field, confocal, and scanning electron microscopy were used to characterize the attachment, spreading and proliferation of these cell types. In case of astrocytes, we found that both cell number and average cell spreading was significantly larger on platinum, compared to silicon surfaces, while silicon surfaces impeded glial proliferation. Nanostructuring did not have a significant effect on either parameter in astrocytes but influenced the orientation of actin filaments and glial fibrillary acidic protein fibers. Neuronal soma attachment was impaired on metal surfaces while nanostructuring seemed to influence neuronal growth cone morphology, regardless of surface material. Taken together, the type of metals tested had a profound influence on cellular responses, which was only slightly modified by nanopatterning.Anita Pongrácz and Katalin Schlett contributed equally to this study.

Hypothermia is a widely used clinical practice for neuroprotection and is a well-established method to mitigate the adverse effects of some clinical conditions such as reperfusion injury after cardiac arrest and hypoxic ischemic encephalopathy in newborns. The discovery, that lowering the core temperature has a therapeutic potential dates back to the early 20th century, but the underlying mechanisms are actively researched, even today. Especially, in the area of neural disorders such as epilepsy and traumatic brain injury, cooling has promising prospects. It is well documented in animal models, that the application of focal brain cooling can effectively terminate epileptic discharges. There is, however, limited data regarding human clinical trials. In this review article, we will discuss the main aspects of therapeutic hypothermia focusing on its use in treating epilepsy. The various experimental approaches and device concepts for focal brain cooling are presented and their potential for controlling and suppressing seizure activity are compared.

Various methods are currently under development to enhance the biocompatibility of neural electrodes and to minimize the reactive gliosis around the implant surface. As cells in their native microenvironment interact with 3D nanoscale topographies of the extracellular matrix, physical modification of implant surfaces may provide an alternative solution to the negative tissue response by imitating the structure of the extracellular matrix, and therefore affecting the attachment and behavior of neurons and glial cells. The attachment of primary mouse astrocytes on nanostructured SU8 polymer surfaces fabricated by e-beam lithography was investigated in our study. We found that attachment of primary mouse astrocytes on silicon-SU8 surfaces is strongly influenced by the surface topography.