Publications by Year: 2025

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a relatively uncommon epilepsy syndrome, characterized by seizures closely related to the sleep cycle. This study aims to explore interictal electroencephalographic (EEG) characteristics in SHE.

METHODS: We compared EEG data from 20 patients with SHE, 20 patients with focal epilepsy (FE), and 14 healthy controls, carefully matched for age, sex, education level, epilepsy duration, and drug-resistant epilepsy.

RESULTS: Our findings revealed distinct patterns of power spectral density in SHE patients during wakefulness and N2 sleep compared to other groups, suggesting potential diagnostic value. During wakefulness, SHE patients showed enhanced frontal lobe power across all frequency bands, but decreased frontal lobe power in low-frequency bands during N2 sleep. Additionally, a positive correlation was found between frontal γ band power and epilepsy duration in SHE patients during N2 sleep but not during wakefulness.

CONCLUSIONS: These findings suggest that interictal EEG abnormalities during wakefulness and N2 sleep might be used as potential biomarkers for the diagnosis of SHE.

SIGNIFICANCE: This study is the first to simultaneously characterize EEG during sleep and wakefulness in SHE patients during interictal periods, with potential utility for diagnosis.

Lower urinary tract symptoms (LUTS) affect approximately 50% of the population over 40 years of age and are strongly associated with obesity and metabolic syndrome. Adipose tissue plays a key role in obesity/metabolic syndrome by releasing adipokines that regulate systemic energy/lipid metabolism, insulin resistance, and inflammation. Adiponectin (ADPN), the most abundant adipokine, modulates energy/metabolism homeostasis through its insulin-sensitizing and antiinflammatory effects. Human plasma ADPN levels are inversely associated with obesity and diabetes. To the best of our knowledge, the role of adipokines such as ADPN in the LUTS associated with obesity/metabolic syndrome remains unknown. We have tested such a possible role in a global ADPN-knockout (Adpn-/-) mouse model. Adpn-/- mice exhibited increased voiding frequency, small voids, and reduced bladder smooth muscle (BSM) contractility, with absence of purinergic contraction. Molecular examination indicated significantly altered metabolic and purinergic pathways. The ADPN receptor agonist AdipoRon was found to abolish acute BSM contraction. Intriguingly, both AMPK activators and inhibitors also abolished BSM purinergic contraction. These data indicate the important contribution of what we believe is a novel ADPN signaling pathway to the regulation of BSM contractility. Dysregulation of this ADPN signaling pathway might be an important mechanism leading to LUTS associated with obesity/metabolic syndrome.

Hypoxic-ischemic (HI) brain injury is a common neurological problem in neonates. The postsynaptic density protein-95 (PSD-95) is an excitatory synaptic scaffolding protein that regulates synaptic function, and represents a potential therapeutic target to attenuate HI brain injury. Syn3 and d-Syn3 are novel high affinity cyclic peptides that bind the PDZ3 domain of PSD-95. We investigated the neuroprotective efficacy of Syn3 and d-Syn3 after exposure to HI in neonatal rodents. Postnatal (P) day-7 rats were treated with Syn3 and d-Syn3 at zero, 24, and 48-h after carotid artery ligation and 90-min of 8 % oxygen. Hemispheric volume atrophy and Iba-1 positive microglia were quantified by cresyl violet and immunohistochemical staining. Treatment with Syn3 and d-Syn3 reduced tissue volume loss by 47.0 % and 41.0 % in the male plus female, and by 42.1 % and 65.0 % in the male groups, respectively. Syn3 reduced tissue loss by 52.3 % in females. D-Syn3 reduced Iba-1 positive microglia/DAPI ratios in the pooled group, males, and females. Syn3 effects were observed in the pooled group and females. Changes in Iba-1 positive microglia/DAPI cellular ratios correlated directly with reduced hemispheric volume loss, suggesting that Syn3 and d-Syn3 provide neuroprotection in part by their effects on Iba-1 positive microglia. The pathogenic cis phosphorylated Thr231 in Tau (cis P-tau) is a marker of neuronal injury. Cis P-tau was induced in cortical cells of the placebo-treated pooled group, males and females after HI, and reduced by treatment with d-Syn3. Therefore, treatment with these peptidomimetic agents exert neuroprotective effects after exposure of neonatal subjects to HI related brain injury.