Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway

The occurrence of epilepsy is a spontaneous and recurring process due to abnormal neuronal firing in the brain. Epilepsy is understood to be caused by an imbalance between excitatory and inhibitory neurotransmitters in the neural network. The close association between astrocytes and synapses can regulate the excitability of neurons through the clearance of neurotransmitters. Therefore, the abnormal function of astrocytes can lead to the onset and development of epilepsy. The onset of epilepsy can produce a large number of inflammatory mediators, which can aggravate epileptic seizures, leading to a vicious cycle. Neurons and glial cells interact to promote the onset and maintenance of epilepsy, but the specific underlying molecular mechanisms need to be further studied. Ciliary neurotrophic factor (CNTF) belongs to the IL‑6 cytokine family and is mainly secreted by astrocytes and Schwann cells. In the normal physiological state, CNTF levels are low, but in an epileptic state, CNTF levels in the serum and tears of patients are elevated. Astrocyte activation plays an important role in epileptic seizures. CNTF activates astrocytes to produce a variety of secreted proteins, which are secreted into the astrocyte culture medium (ACM), thus forming a distinct culture medium (CNTF‑ACM) that can be used to study the effect of astrocytes on neurons <i>in vitro</i>. CNTF‑activated astrocytes increase the secretion of the pro‑inflammatory factor IL‑6. In the present study, CNTF‑ACM was applied to primary cerebral cortical neurons to observe the specific effects of IL‑6 in CNTF‑ACM on neuronal activity and excitability. The results suggested that CNTF‑ACM can reduce neuronal activity via the IL‑6/IL‑6R pathway, promote neuronal apoptosis, increase Ca²⁺ inflow, activate the large conductance calcium‑activated potassium channel and enhance neuronal excitability. The results of the present study further revealed the functional changes of astrocytes after CNTF activated astrocytes and the effects on neuronal activity and excitability, thereby providing new experimental evidence for the role of communication between astrocytes and neurons in the mechanism of epileptic seizures.