Glioblastoma multiforme is the most malignant and aggressive type of brain tumor, with a mean life expectancy of less than 15 months. This is due in part to the high resistance to apoptosis and moderate resistant to autophagic cell death in glioblastoma cells, and to the poor therapeutic response to conventional therapies. Autophagic cell death represents an alternative mechanism to overcome the resistance of glioblastoma to pro-apoptosis-related therapies. Nevertheless, apoptosis induction plays a major conceptual role in several experimental studies to develop novel therapies against brain tumors. In this review, we outline the different components of the apoptotic and autophagic pathways and explore the mechanisms of resistance to these cell death pathways in glioblastoma cells. Finally, we discuss drugs with clinical and preclinical use that interfere with the mechanisms of survival, proliferation, angiogenesis, migration, invasion, and cell death of malignant cells, favoring the induction of apoptosis and autophagy, or the inhibition of the latter leading to cell death, as well as their therapeutic potential in glioma, and examine new perspectives in this promising research field.
The incidence of epilepsy is high in developing countries where malnutrition is prevalent. Although malnutrition is not a direct cause of seizures, chronic malnutrition may predispose the brain to seizures. In large undernourished human groups from Latin America, the most common sources of food are corn and corn derivatives. We used a rat model of chronic malnutrition, in which corn tortillas were the only solid food intake, to study the possible influence of malnutrition at late stages of brain development on the dynamics of experimental seizures induced by pentylenetetrazole (PTZ). The threshold and does of PTZ required to produce seizures were greatly reduced in malnourished rats. The model of malnutrition used in the study imitates a form of malnutrition common among large numbers of humans. Our results suggest that chronic malnutrition early in life induces changes that lower the seizure threshold and leave the brain more susceptible to seizures. Whether this observation relates to the high incidence of epilepsy in underdeveloped countries remains to be determined.
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