RESUMO
Glioblastoma remains a poor‐prognosis cancer. We review research showing evanescent opening of the blood‐brain barrier, BBB, after electroconvulsive treatment, ECT. ECT as currently used in psychiatry for treatment‐resistant depression has been in continuous use throughout the world since introduction in the late 1930’s. Post-ictal BBB opening phenomenon might be safe enough to use to deliver chemotherapeutic agents that would not otherwise cross the BBB. Although the main mass of tumor in glioblastoma has a relatively leaky BBB, the invasive paucicellular migratory microsatellite glioblastoma cells that become the origin of recurrent tumor are supplied by normal poorly‐permeable capillaries, preventing ready access of potentially useful chemotherapy drugs like doxorubicin or methotrexate. These microsatellites go on to kill. Modern ECT uses deep neuromuscular blockade and cardiovascular stabilizing drugs such that muscular contractions and increases in intracranial pressure are minimized, yet the electroencephalogram shows a typical grand mal seizure. Post‐ECT BBB opening allows transgression of > 4 kDa peptides, potentially comfortable enough to give free access to brain tissue of doxorubicin or methotrexate for example. Even drugs that are said to cross the BBB, such as temozolomide, the current mainstay chemotherapy drug in glioblastoma, do so only at ~20% of plasma levels. Many potentially useful drugs achieve brain tissue levels <1% of blood levels. We conclude that if careful step-wise study can establish safety, by delivering chemotherapy immediately after ECT we may open new and more effective treatment avenues for glioblastoma.
RESUMO
The intercellular adhesion molecule is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) from normal control children as well as from children with Guillain-Barré syndrome (GBS), with Coxsackie A9 virus meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using the immunodiffusion technique in both biological fluids. Increased sICAM-1 values in CSF in patients with GBS correspond to an increase of the albumin CSF/serum quotient. In contrast, in inflammatory diseases like S. pneumoniae and Coxsackie A9 virus meningoencephalitis an increased brain-derived fraction was observed. In particular cases these values are 60-65 percent and 70-75 percent respectively. The results indicate an additional synthesis of sICAM-1 in subarachnoidal space during central nervous system (CNS) inflammatory process. An important role of sICAM-1 in the transmigration of different cell types into CSF during CNS inflammation in children with S. pneumoniae and Coxsackie A9 meningoencephalitis may be suggested.
La molécula de adhesión intercelular es una glicoproteína que pertenece a la superfamilia de las inmunoglobulinas. Se estudiaron los niveles de molécula de adhesión intercelular tipo 1 soluble (sICAM-1) en suero y líquido cefalorraquídeo (LCR) de niños con meningoencefalitis por Streptococcus pneumoniae y por Coxsackie A9 al igual que en niños con sindrome de Guillain-Barré (SGB). sICAM-1 fue cuantificado por ensayo inmunoenzimático y la albúmina por inmunodifusión en ambos líquidos biológicos. Los valores incrementados de sICAM-1 en LCR en los pacientes con GBS corresponden a valores aumentados de razón LCR/suero de albúmina. En contraste, en las enfermedades inflamatorias como las meningoencefalitis por S. pneumoniae y por Coxsackie A9 se observa un incremento en la fracción derivada del cerebro. En casos particulares los valores se incrementan hasta un 60-65 por ciento y 70-75 por ciento respectivamente. Los resultados indican una síntesis adicional de sICAM-1 en el espacio subaracnoideo durante el proceso inflamatorio del sistema nervioso central (SNC). Esto puede sugerir un importante papel del sICAM-1 en la transmigración de diferentes tipos celulares en el LCR durante la inflamación del SNC en niños con meningoencefalitis por S pneumoniae y coxsackie A9.