The role of necroptosis in neurosurgical diseases

Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

Expression of death cellular receptors FAS/CD95 and DR4 during porcine placentation / Expresión de los receptores de muerte celular FAS/CD95 y DR4 durante la placentación porcina

Apoptosis is a permanent and dynamic physiological process by which an organism eliminates the undesirable cells without causing an inflammatory response. The objective of this work was to study the expression of FAS, DR4 and other members of the TNF-R1 superfamily extrinsic route apoptotic receptors the DNA fragmentation and the cellular apoptosis in placental samples at the early, mid and late pregnancy on +/- 30, +/- 55 and +/- 114 gestational days, respectively. We used placental histological sections of samples fixed in buffered saline formaldehyde. Immunohistochemical techniques were performed to detect the apoptotic receptors, whereas the DNA fragmentation was detected by TUNEL reaction and apoptotic cellular ultrastructure was detected by TEM conventional techniques. Apoptosis related receptors were immunolocalized in the early pig gestation and correlated with apoptosis, suggesting a role in the cellular remodelling of the placenta. At gestation day 55, apoptosis might be correlated to FAS route, but not by DR4-mediating pathway. At the end of gestation, increased apoptosis and both receptors markers were detected showing cellular death due to the extrinsic route through FAS and DR4 receptors. In conclusion, the immunolocalization of FAS and TNF R-1 receptors along the pig placental development correlates with TUNEL reaction and with apoptotic ultrastructure observed by TEM and seems to occur through different pathways along gestation.

La apoptosis es un proceso fisiológico, dinámico y permanente a través del cual un organismo elimina células indeseables sin provocar una respuesta inflamatoria. El objetivo del presente trabajo fue estudiar la expresión de los receptores de la vía extrínseca de apoptosis, FAS, DR4 y otros miembros de la superfamilia TNF-R1, la fragmentación del ADN y la apoptosis celular a través de TEM, en muestras placentarias del inicio, la mitad y el final de la gestación, hacia el día +/- 30, +/- 55 y +/- 114 de preñez, respectivamente. Se realizaron cortes histológicos de las muestras placentarias fijadas en formol tamponado. Para la detección de los receptores de apoptosis se realizaron técnicas inmunohistoquímicas, para el estudio de la fragmentación del ADN se utilizó el ensayo TUNEL y para el análisis de la ultraestructura celular apoptótica la técnica convencional de TEM. La inmunolocalización de los receptores de muerte celular al inicio de la preñez porcina sugiere el rol de la apoptosis en la remodelación celular placentaria. Hacia el día 55 de preñez, la apoptosis detectada ocurriría únicamente a través de la vía del receptor FAS, no del receptor DR4. Al final de la gestación, se detectó un incremento de la apoptosis y la expresión de ambos receptores, indicando que la muerte celular a través de la vía de señalización extrínseca estaría inducida por los receptores FAS y DR4. En conclusión, la inmunolocalización de los receptores FAS y otros miembros del TNF-R1, los resultados de TUNEL y la ultraestructura celular apoptótica observada en la placentación porcina, indican que la apoptosis detectada ocurre por diferentes vías de inducción a lo largo de la gestación.

Apoptosis and progression of hepatic fibrosis in hepatitis C patients

Hepatitis C is a worldwide endemic disease, affecting roughly 200 million people. It has a variable prognosis, depending on the progression to fibrosis. During the last five years, the importance of apoptosis for the pathogenesis of various diseases, including hepatitis, has been recognized. It has been suggested that an increase in T cell-apoptosis during a hepatitis C virus infection is the cause of impaired regulation of the immune cellular response, helping to maintain infection. Thus, the interest in discovering the probable mechanisms by which the hepatitis C virus perpetuates in the liver, and to determine the conditions that predispose for progression of this disease, makes investigation of apoptosis in hepatic injury of great interest. We have made an overview of the various mechanisms by which the cell, more specifically the hepatic cell, is affected by apoptosis, and how it interacts with the hepatitis C virus and the immune system.