An improvement in the communication process contributes to a decrease in the levels of anxiety, and consequently to enhancement of the well-being of these patients.

Hypoxic pseudopalisades are a pathological hallmark of human glioblastoma, which is linked to tumour malignancy and aggressiveness. Yet, their function and role in the tumour development have scarcely been explored. It is thought that pseudopalisades are formed by malignant cells escaping from the hypoxic environment, although evidence of the immune component of pseudopalisades has been elusive. In the present work, we analyse the immunological constituent of hypoxic pseudopalisades using high-resolution three-dimensional confocal imaging in tissue blocks from excised tumours of glioblastoma patients and mimic the hypoxic gradient in microfluidic platforms in vitro to understand the cellular motility. We visualize that glioblastoma-associated microglia and macrophages abundantly populate pseudopalisades, displaying an elongated kinetic morphology across the pseudopalisades, and are oriented towards the necrotic focus. In vitro experiments demonstrate that under hypoxic gradient, microglia show a particular motile behaviour characterized by the increase of cellular persistence in contrast with glioma cells. Importantly, we show that glioblastoma-associated microglia and macrophages utilize fibres of glioma cells as a haptotactic cue to navigate along the anisotropic structure of the pseudopalisades and display a high phagocytic activity at the necrotic border of the pseudopalisades. In this study, we demonstrate that glioblastoma-associated microglia and macrophages are the main immune cells of pseudopalisades in glioblastoma, travelling to necrotic areas to clear the resulting components of the prothrombotic milieu, suggesting that the scavenging features of glioblastoma-associated microglia and macrophages at the pseudopalisades serve as an essential counterpart for glioma cell invasion.

Summary:A means to avoid the pharmacokinetic problems affecting the anti-epileptic drugs may be their direct intracerebroventricular (ICV) or intracerebral delivery. This approach may achieve a greater drug concentration at the epileptogenic area while minimizing it in other brain or systemic areas, and thus it could be an interesting therapeutic alternative in drug-resistant epilepsies. The objective of this article is to review a series of experiments, ranging from actute ICV injection to continuous intracerebral infusion of anti-epileptic drugs or grafting of neurotransmitter producing cells, in experimental models, especially in the kindling model of epilepsy in the rat.Acute ICV injection of phenytoin, phenobarbital or carbamacepine is able to diminish the intensity of kindling seizures, but it is also associated with a high neurologic toxicity, especially phenobarbital. Continuous ICV infusion of anti-epileptic drugs can effectively control seizures, but neurologic toxicity is not improved compared with systemic delivery. However, systemic toxicity may be improved, as in the case of valproic acid, whose continuous ICV infusion results in very low plasmatic or hepatic drug concentrations. Continuous intracerebral infusion at the epileptogenic area was studied as an alternative to minimize neurologic toxicity. Thus, intra-amygdalar infusion of gamma-aminobutyric acid (GABA) controls seizures with minimal neurotoxicity in amygdala-kindled rats. Similarly, continuous infusion of GABA into the dorsomedian nucleus of the thalamus improves seizure spread, while not affecting the local epileptogenic activity at the amygdala. Grafting of GABA releasing cells may reduce kindling parameter severity without behavioral side effects.We may conclude that ICV or intracerebral delivery of antiepileptic drugs or neurotransmitters may be a useful technique to modulate epilepsy.

Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival. However, some precautions should be taken regarding Gliadel implantation. We report three cases in whom patients with glioblastoma multiforme were implanted with fibrin glue-secured Gliadel after the lateral ventricles had been opened, and who later developed severe hydrocephalus leading to death. Although Gliadel may be an important adjunct to treatment, opening of the ventricles during surgery as part of its application should be considered a contra-indication.