Changes in autonomic nervous function and influencing factors in a rat insular cortex electrical kindling model.

In mammals, the insular cortex plays an important role in autonomic regulation. In patients with insular epilepsy, seizures are always accompanied by autonomic changes. Accordingly, we aimed to establish an electrical kindling model in autonomic-mediating areas of the insular cortex, and to conduct a long-term observation of epileptic genesis in these animals until sudden unexpected death. To establish this model in adult rats, we implanted stimulation electrodes in the granular cell layer of the insular cortex, which controls the heart rate (HR) and respiratory rate (RR). Subsequently, seizure was induced successfully in 92.3 % of the rats, and typical autonomic changes were observed during these seizures. Interestingly, the model was established more easily in older rats, and the rats in which electrical stimulation led to a greater reduction in the HR. Moreover, death occurred in 25 % of the kindled rats. In conclusion, our kindling model demonstrates the ability of insular cortex stimulation to generate epilepsy. Our model thus offers a practical tool for studies of the role of the insular cortex in sudden unexpected death in epilepsy.

Isoflurane-Induced Burst Suppression Is a Thalamus-Modulated, Focal-Onset Rhythm With Persistent Local Asynchrony and Variable Propagation Patterns in Rats.

Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology. Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats. Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within <100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection. Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.

The insula lobe and sudden unexpected death in epilepsy: a hypothesis.

Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with refractory epilepsy, particularly those with chronic epilepsy. The physiopathological mechanisms underlying SUDEP have not been elucidated. Autonomic dysregulation of cardiac or respiratory function is thought to underlie SUDEP. Here, we present a summary of available evidence on the involvement of the insular lobe in the regulation of cardiorespiratory function. Ictal discharge that originates in the cortex can, primarily or secondarily, involve the insula lobe through epileptogenic signal networks, leading to cardiorespiratory dysfunction, central apnoea, arrhythmias, and sudden death in patients with epilepsy. Thus, the insula lobe appears to be instrumental in the causation of SUDEP.

Mesenchymal stem cells moderate immune response of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by lack of insulin and irreversible destruction of islet ß cells. In order to alleviate the symptoms, lifelong exogenous insulin administration has been the primary treatment of T1DM. In recent years, as a novel promising therapy, the transplantation of mesenchymal stem cells (MSCs) with or without pancreatic islets has achieved great therapeutic effects in animal models due to their multipotency along with their secretion of cytokines, angiogenic factors and immunomodulatory substances. There is plenty of evidence showing that MSCs can delay T1DM onset, reverse hyperglycemia after onset and increase insulin production. To date, the immunoregulation and immunosuppression of MSCs have been widely proved but the exact mechanisms are still not clear enough. Therefore, in this review, we mainly discuss the immunologic mechanism of MSCs in moderating the immune response of T1DM.