An Animal Model to Study the Clinical Significance of Interictal Spiking

Abstract

Interictal spikes (IIS) are paroxysmal discharges commonly observed in patients with epilepsy which represent an abnormally-synchronized population of hyperexcitable neurons firing as an aggregate. Due to conflicting studies on the clinical significance of IIS, research focusing on IIS has been sparse. However, recent attention on IIS has increased for patients undergoing surgery for intractable epilepsy as a means to identify epileptic foci for surgical resection. There is growing evidence that IIS are not asymptomatic as has been commonly accepted. Other than epilepsy, IIS have been associated with a wide range of behavioral and psychiatric disorders, including attention deficit disorder, anxiety disorders and psychoses. For these reasons, a well-characterized animal model of interictal spiking which accurately mimics the human phenomenon would be a valuable tool to gain insights both into the pathophysiology of epilepsy as well as a broad variety of human neuropsychiatric diseases. Here, we review the literature on the clinical significance of IIS in humans and on animal models where IIS has been observed. We then demonstrate the utility of using tetanus toxin to generate a reproducible pattern of progressive IIS for future studies into their clinical significance.

Experimental focal neocortical epilepsy is associated with reduced white matter volume growth: results from multiparametric MRI analysis

“…In our study, normal animals were used in which epilepsy was induced during late adolescence, without prior status epilepticus, and unaccompanied by treatment with antiepileptic drugs. Since the intracortical injection of tetanus itself does not cause significant microstructural tissue damage (Barkmeier and Loeb 2009), we propose that white matter pathology in this model can be at least partially attributed to the repeated seizures or an interaction between normal myelination of white matter fibers and repeated seizures. Nonetheless, this hypothesis remains to be confirmed in studies that will include more (earlier) time points and focus on distinct periods within the neurodevelopmental time frame including adolescence and late adulthood.…”

Coalescence of deep and superficial epileptic foci into larger discharge units in adult rat neocortex

“…The observation of broader fields in superficial layers of this acute preparation is novel and may provide an electrophysiological correlate to molecular observations indicating MAP-kinase/CREB pathway expression in superficial layers of chronic human epileptic cortex and animal models of neocortical epilepsy (Rakhade et al, 2005, 2007; Barkmeier and Loeb, 2009; Barkmeier et al, 2012; Beaumont et al, 2012; Dachet et al, 2015). MAP-kinase CREB is a candidate to play a role in the development of interictal spikes measured from surface potential and may be due so through the strengthening of synaptic connections (Thomas and Huganir, 2004).…”

Raised Activity of L-Type Calcium Channels Renders Neurons Prone to Form Paroxysmal Depolarization Shifts

“…However, because evidence is continuously accumulating that PDS represent important elements in epileptogenesis (Dyhrfjeld-Johnsen et al 2010; Staley et al 2011), LTCCs may provide valuable targets for anti-epileptogenic rather than anti-epileptic therapy. Moreover, interictal spikes have besides epileptogenesis also been implicated in other neurologic disorders, such as attention deficit disorder, anxiety disorders and psychoses (for a review see Barkmeier and Loeb 2009). Hence, new therapeutic strategies to counteract PDS may serve in the therapeutic prophylaxis of acquired epilepsies but could also be of value in other neuropathologies.…”