Neurological disorders (NDs) are diseases of the central and peripheral nervous system that affected the hundreds of millions of people worldwide. Temporal lobe epilepsy (TLE) is a common NDs with hallucinations and disturbance of consciousness that cause the abnormal neurological activity in any part of brain. Neuroinflammation (NI) has been identified in epilepsy-related tissue from both experimental and clinical evidence and suspected to participate in the formation of neuronal cell death, reactive gliosis and neuroplastic changes in the hippocampus, may contribute to epileptogenesis. The NI is tightly regulated by microglia, but it is thought that excessive or chronic microglial activation can contribute to neurodegenerative processes. Therefore, the modulation of microglia responses may provide a therapeutic target for the treatment of severe or chronic NI conditions. Although the condition responds well to antiepileptic drugs (AEDs), there are still unresponsive to AEDs in about 1/3 of cases. Neural stem cells are the origin of various types of neural cells during embryonic development. Currently, many results of stem cell therapies in the animal experiments and clinical trials were demonstrated the efficacious therapeutic effects in the attenuated symptoms of ND. Therefore, the combined application therapies of stem cells and drugs may be a promising candidate for the therapeutic strategies of NDs, especially TLE.
Part of the book: Novel Perspectives of Stem Cell Manufacturing and Therapies
Microglia typically exist in a resting state of a mature brain and monitors the brain environment. In response to brain injuries or immunological stimuli, however, microglia are readily activated. In their activated state, they can serve diverse beneficial functions essential for enhancing neuron survival through the release of trophic and anti-inflammatory factors. Under certain circumstances, such as sustained epilepsy, however, microglia become overactivated and can induce significant and highly detrimental neurotoxic effects by the excessive production of a large array of cytotoxic factors, such as nitric oxide and proinflammatory cytokines. Neuroinflammation has been identified in epileptogenic tissue and is suspected of participating in epileptogenesis. Recent evidence has shown the effects of anti-inflammation and protection against ischemic brain injury by inhibiting soluble epoxide hydrolase (sEH) pharmacologically and genetically. We assume that sEH inhibition might be also beneficial to prevent inflammatory processes caused by seizures and subsequent chronic epilepsy. In the present study, we investigated whether sEH is involved in overactivated microglia-induced neuroinflammation and subsequent epileptogenesis in a mouse model of temporal lobe epilepsy. Overactivated microglia will be detected by using imaging techniques. It is hoped that the results of the present study would provide a better understanding of the roles of sEH and microglia in epileptogenesis.
Part of the book: Epilepsy - Seizures without Triggers