bioRxiv Science⌕ Search

Biology subjects

Leemburg, S.

Publications and source records attributed to Leemburg, S..

4 recordsLinked to original sources

LPS-induced sepsis disrupts brain activity in a region- and vigilance-state specific manner

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis and the systemic inflammatory response syndrome that leads to lasting consequences in survivors. It manifests as early EEG changes, that are region-, time- and state-specific, possibly reflecting distinct mechanisms of injury. Here, we investigated the effects of 5mg/kg lipopolysaccharide (LPS) on hippocampal and cortical sleep-wake states, oscillatory and non-oscillatory neuronal activity, as well as on within and between state dynamics using state-space analysis. LPS induced rapid-onset severe temporal and spatial vigilance state fragmentation, which preceded all other spectral changes by [~]90 minutes. Thereafter, LPS led to specific destabilization and increased delta oscillatory activity in wakefulness, but not NREM sleep, although state transitions remained largely normal. Instead, reduced NREM delta power resulted from aperiodic spectrum changes. LPS specifically reduced higher frequency hippocampal gamma oscillations (60-80Hz peak) in wakefulness, but not cortical high gamma or lower frequency gamma oscillations. These results suggest that disruption of sleep-wake patterns could serve as an early indicator of sepsis and associated encephalopathy, independent of spectral changes. Moreover, treatment aimed at stabilizing vigilance states in early stages of sepsis might prove to be a novel option preventing the development of further pathological neurophysiology, as well as limiting inflammation-related brain damage.

neuroscience↗

Sepsis-induced brain state instability

Sepsis-associated brain dysfunction (SABD) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome. It is associated with high mortality and a majority of survivors suffer long-term neurological consequences. Here, we aimed at better understanding the effects of SABD on oscillatory brain states in an acute rat model of sepsis induced by high dose LPS (10 mg/kg). To focus on intrinsically generated brain state dynamics, we used a urethane model that spares oscillatory activity in REM- and NREM-like sleep states. Soon after the intraperitoneal LPS injection we observed a robust instability of both oscillatory states resulting in tripling amount of state transitions that lasted for several hours, although the overall time spent in either state did not change. Analysis of power spectra showed opposing shifts in low frequency oscillations (1-9 Hz) that resulted in increased similarity between both states in 2-D state space. The described spectral characteristics of sepsis-induced EEG state instability might point to a mechanism underlying severe sleep fragmentation as described both in sepsis patients and in SABD animal models.

neuroscience↗

Lempel-Ziv complexity of the EEG predicts long-term functional recovery after stroke in rats

Non-linear complexity of the EEG signal can be used to detect abnormal brain function relating to behavioral deficits. Here, we compare the effects of experimental stroke on EEG complexity using Lempel-Ziv complexity analysis (LZC) and multiscale entropy analysis (SampEn).\n\nEEG was recorded in bilateral motor cortex at baseline and during a 30-day recovery period after distal middle cerebral artery occlusion in rats. Motor function was assessed using a single pellet reaching task. Stroke caused an acute drop in both LZC and SampEn in the ipsilesional hemisphere in wakefulness, NREM and REM sleep, as well as reduced pellet reaching success. SampEn reductions persisted for at least 10 days post-stroke, whereas LZC had returned to baseline levels by day 4. EEG complexity in the contralesional hemisphere and in sham-operated animals were unaffected.\n\nIf EEG complexity reflects post-stroke brain function, post-stroke asymmetry could be used to predict behavioral recovery. In rats, acute LZC asymmetry was significantly correlated with the amount of motor function recovery by post-stroke day 31, but SampEn asymmetry was not. EEG LZC may thus be a useful tool for predicting functional recovery after stroke. MSE could be effective in identifying cortical dysfunction, but does not reflect behavioral outcomes.

neuroscience↗

Power spectrum slope and motor function recovery after focal cerebral ischemia in the rat

EEG changes across vigilance states have been observed after ischemic stroke in patients and experimental stroke models, but their relation to functional recovery remains unclear. Here, we evaluate motor function, as measured by single pellet reaching (SPR), as well as local EEG changes in NREM, REM and wakefulness during a 30-day recovery period after middle cerebral artery occlusion (MCAO) or sham surgery in rats. Small cortical infarcts resulted in poor SPR performance and induced widespread changes in EEG spectra in the ipsilesional hemisphere in all vigilance states, without causing major changes in sleep-wake architecture. Ipsilesional 1-4 Hz power was increased after stroke, whereas power in higher frequencies was reduced, resulting in a steeper slope of the power spectrum. Multielectrode array analysis of ipsilesional M1 showed that these spectral changes were present on the microelectrode level throughout M1 and were not related to increased synchronization between electrodes. Spectrum slope was significantly correlated with post-stroke motor function.

neuroscience↗