Porcine Model of Cerebral Ischemic Stroke Utilizing Intracortical Recordings for the Continuous Monitoring of the Ischemic Area.

PURPOSE: Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. METHODS: Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. RESULTS: Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO2, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. CONCLUSIONS: The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.

Morphology and morphometry of the ulnar nerve in the forelimb of pigs.

The knowledge of the morphology and morphometry of peripheral nerves is essential for developing neural interfaces and understanding nerve regeneration in basic and applied research. Currently, the most adopted animal model is the rat, even though recent studies have suggested that the neuroanatomy of large animal models is more comparable to humans. The present knowledge of the morphological structure of large animal models is limited; therefore, the present study aims to describe the morphological characteristics of the Ulnar Nerve (UN) in pigs. UN cross-sections were taken from seven Danish landrace pigs at three distinct locations: distal UN, proximal UN and at the dorsal cutaneous branch of the UN (DCBUN). The nerve diameter, fascicle diameter and number, number of fibres and fibre size were quantified. The UN diameter was larger in the proximal section compared to the distal segment and the DCBUN. The proximal branch also had a more significant number of fascicles (median: 15) than the distal (median: 10) and the DCBUN (median: 11) segments. Additionally, the mean fascicle diameter was smaller at the DCBUN (mean: 165 µm) than at the distal (mean: 197 µm) and proximal (mean: 199 µm) segments of the UN. Detailed knowledge of the microscopical structure of the UN in pigs is critical for further studies investigating neural interface designs and computational models of the peripheral nervous system.

The effect of peripheral high-frequency electrical stimulation on the primary somatosensory cortex in pigs.

This study implements the use of Danish Landrace pigs as subjects for the long-term potentiation (LTP)-like pain model. This is accomplished by analyzing changes in the primary somatosensory cortex (S1) in response to electrical stimulation on the ulnar nerve after applying high-frequency electrical stimulation (HFS) on the ulnar nerve. In this study, eight Danish Landrace pigs were electrically stimulated, through the ulnar nerve, to record the cortically evoked response in S1 by a 16-channel microelectrode array (MEA). Six of these pigs were subjected to HFS (four consecutive, 15 mA, 100 Hz, 1000 µs pulse duration) 45 min after the start of the experiment. Two pigs were used as control subjects to compare the cortical response to peripheral electrical stimulation without applying HFS. Low-frequency components of the intracortical signals (0.3-300 Hz) were analyzed using event-related potential (ERP) analysis, where the minimum peak during the first 30-50 ms (N1 component) in each channel was detected. The change in N1 was compared over time across the intervention and control groups. Spectral analysis was used to demonstrate the effect of the intervention on the evoked cortical oscillations computed between 75 ms and 200 ms after stimulus. ERP analysis showed an immediate increase in N1 amplitude that became statistically significant 45 mins after HFS (p < 0.01) for the intervention group. The normalized change in power in frequency oscillations showed a similar trend. The results show that the LTP-like pain model can be effectively implemented in pigs using HFS since the cortical responses are comparable to those described in humans.