Ricerc@Sapienza

Compared with the Control group, the Glioblastoma group of mice may exhibit EEG markers reflecting an abnormal cortical neural synchronization and functional connectivity due to the effect of the brain tumor. This outcome would represent the first evidence of the effect of brain glioblastoma on neurophysiological oscillatory mechanisms underpinning the cortical arousal in mice. Furthermore, it may validate the present model of neurophysiological research for testing new interventions against glioblastoma in mice, namely new drugs and their interactions with an enriched environment including social, cognitive, and motor opportunities.
The step-forward of the proposed neurophysiological research model is evident when the extant field literature is considered. A bulk of previous studies has applied EEG markers to investigate neurophysiological or neuropathological mechanisms in mouse models. For example, several studies found abnormal EEG activity in AD mouse models with a mutation in the gene regulating APP [7, 8, 9, 10, 11, 12, 13]. These studies reported epileptiform and hypersynchronous EEG activities in transgenic strains [14, 15, 16]. However, those EEG results reflected a mixture of several behavioral states (active, passive, sleep) and instinctual activity (i.e. eating, drinking, mating, etc.). Therefore, they did not represent an optimal neurophysiological research model for the application to brain tumors.
In the research on brain tumors, such as glioblastoma, a very exhaustive literature has explored the pathological mechanisms related to tumor proliferation at the microscopic level, investigating several factors such as microglia activation, neuroinflammatory response or the activation of immune effector [17, 18]. However, no updated studies evaluated the relationship between underlying tumor-related molecular processes and the abnormalities of neurophysiological oscillatory mechanisms underpinning the cortical arousal and vigilance in wakefulness.
The mentioned state-of-the-art is surprising as EEG methodology has repeatedly been used to investigate epilepsy associated with brain tumors. Indeed, epilepsy is considered one of the most common symptoms in patients with brain tumors, with a development of seizure at the onset symptom (20-40%) or later (20-45%) during the disease [19]. The recurrence of epilepsy onset is inversely correlated to malignancy, with the highest incidence (from 65-95%) occurring in low-grade tumors (astrocytoma, oligodendroglioma, and mixed astrocytoma I and II WHO, and meningiomas), and the lowest incidence (from 15-25%) occurring in malignant gliomas. The onset of seizures seems to indicate a more favorable prognosis. This prediction is probably due to the early diagnosis resulting from the visible manifestation of the seizures, a more superficial position of the tumor generating the seizures, and the favorable histology typically associated with slow-growing tumors. Of note, glioblastoma is a high-grade brain tumor typically not related to an evident subclinical or clinical epileptiform activity. However, the present methodological approach may unveil some peculiar subclinical alterations of neurophysiological oscillatory mechanisms underpinning the cortical arousal and vigilance not captured by the standard methodology applied in epilepsy research.

Essential references
[7] Minkeviciene R et al. J Neurosci. 2009
[8] Sanchez A et al. J Alzheimers Dis. 2012
[9] Verret L et al. Neurobiol Aging. 2013
[10] Schneider F et al. Physiol Behav. 2014
[11] Palop JJ et al. Neuron. 2007
[12] Ziyatdinova S et al. Epilepsy Res. 2011
[13] Corbett BF et al. J Neurosci. 2013
[14] van Praag H et al. Nat Rev Neurosci. 2000
[15] Wang J et al. Brain Res. 2002
[16] Nithianantharajah J, Hannan AJ. Nat Rev Neurosci. 2006
[17] Sowers et al. Adv Exp Med Biol. 2014
[18] Ha et al. Neuroimmunol Neuroinflammation 2014
[19] Maschio Curr Neuropharmacol. 2012