Experimental chronic sleep fragmentation alters seizure susceptibility and brain levels of interleukins 1β and 6

Abstract

Brain hyperexcitability in sleep apnea is believed to be provoked by hypoxemia, but sleep fragmentation can also play a significant role. Sleep fragmentation can trigger inflammatory mechanisms. The aim of this research was to investigate the effects of chronic sleep fragmentation on seizure susceptibility and brain cytokine profile. Chronic sleep fragmentation in male rats with implanted EEG electrodes was achieved by the treadmill method. Rats were randomized to: treadmill control (TC); activity control (AC) and sleep fragmentation (SF) group. Convulsive behavior was assessed 14 days later by seizure incidence, latency time and seizure severity during 30 min following lindane administration. The number and duration of EEG ictal periods were determined. Levels of IL-1β and IL-6 were measured in the animals' serum and brain structures (hippocampus, thalamus and cerebral cortex), in separate rat cohort that underwent the same fragmentation protocol except lindane administration. Incidence and severity of seizures were significantly increased, while latency was significantly decreased in SF+L compared with TC+L group. Seizure latency was also significantly decreased in SF+L compared to AC+L group. The number and duration of ictal periods were increased in the SF+L compared to the AC+L group. IL-1β was significantly increased in the thalamus, cortex and hippocampus in the SF compared to the AC and TC groups. IL-6 was statistically higher only in the cortex of SF animals, while in the thalamic or hippocampal tissue, no difference was observed between the groups. It could be concluded that fourteen-day sleep fragmentation increases seizure susceptibility in rats and modulates brain production of IL-1β and IL-6.

Obstructive sleep apnea induced bilateral tonic- clonic seizure of unknown origin: A case series of a novel association

“…The deficiency of synapsin-IIa and IIb isoforms is crucially associated with epileptiform and seizure-related phenomena due to its regulation of neurotransmitter release. 17 Grubač et al 18 reported that chronic sleep fragmentation increases seizure susceptibility and modulates neuronal production of IL-1β and IL-6. According to Grippo et al, 19 the PaCO2 level in patients with obstructive sleep apnea may interact on various ion channels or metabolic pathways, changing the excitability of the motor cortex and modifying excitatory and inhibitory cortical circuits.…”

Screening of differentially expressed genes in children with cerebral palsy and the construction of a network of the effective components of traditional Chinese medicine

“…IL-6 is an important neuroinflammatory factor that mediates brain inflammatory lesions and amyloidosis, and is associated with a variety of brain diseases, including Alzheimer's disease, and autism (10,11). IL-6 is associated with periventricular leukomalacia and may affect neurodevelopment and increase the risk of cerebral palsy (12). Studies have shown that in children with cerebral palsy, cytokines are dysregulated, and plasma TNF levels are elevated (13,14).…”

Modulating Expression of Endogenous Interleukin 1 Beta in the Acute Phase of the Pilocarpine Model of Epilepsy May Change Animal Survival

“…In addition, under physiological conditions, Il1b seems to modulate several functions in the CNS, such as regulating sleep (De Sarro et al 1997 ; Krueger et al 1998 ) and promoting learning and long-term potentiation (LTP) (Bellinger et al 1993 ; Schneider et al 1998 ; Ikegaya et al 2003 ; del Rey et al 2013 ). Chronic overexpression of Il1b in brain areas such as the hippocampus have been implicated in impaired spatial memory (Moore et al 2009 ) and in contextual fear memory (Matousek et al 2010 ) in conditional transgenic mice, and with seizure susceptibility in animal models of sleep fragmentation (Grubac et al 2021 ) and prostatitis (Sutulovic et al 2019 ). By contrast, transgenic mice with deficient Il1b signaling or pharmacological inhibition of CNS Il1b also present with memory and learning impairment (Avital et al 2003 ; Goshen et al 2007 ).…”