Altered hippocampal myelinated fiber integrity in a lithium-pilocarpine model of temporal lobe epilepsy: A histopathological and stereological investigation

Abstract

The damage of white matter, primarily myelinated fibers, in the central nervous system (CNS) of temporal lobe epilepsy (TLE) patients has been recently reported. However, limited data exist addressing the types of changes that occur to myelinated fibers inside the hippocampus as a result of TLE. The current study was designed to examine this issue in a lithium-pilocarpine rat model. Investigated by electroencephalography (EEG), Gallyas silver staining, immunohistochemistry, western blotting, transmission electron microscopy, and stereological methods, the results showed that hippocampal myelinated fibers of the epilepsy group were degenerated with significantly less myelin basic protein (MBP) expression relative to those of control group rats. Stereological analysis revealed that the total volumes of hippocampal formation, myelinated fibers, and myelin sheaths in the hippocampus of epilepsy group rats were decreased by 20.43%, 49.16%, and 52.60%, respectively. In addition, epilepsy group rats showed significantly greater mean diameters of myelinated fibers and axons, whereas the mean thickness of myelin sheaths was less, especially for small axons with diameters from 0.1 to 0.8µm, compared to control group rats. Finally, the total length of the myelinated fibers in the hippocampus of epilepsy group rats was significantly decreased by 56.92%, compared to that of the control group, with the decreased length most prominent for myelinated fibers with diameters from 0.4 to 0.8µm. This study is the first to provide experimental evidence that the integrity of hippocampal myelinated fibers is negatively affected by inducing epileptic seizures with pilocarpine, which may contribute to the abnormal propagation of epileptic discharge.

Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis

“…The four rats that did not display SRS after 80 days were excluded. Similarly to previously reported findings (Goffin et al, 2007;Ye et al, 2013), SRS tended to occur in clusters with a duration of less than one min for each seizure. Fig.…”

“…The myelin sheath is critical for interneuronal communication, and the integrity of myelin is crucial for maintaining normal neuronal network function and sequential electrical impulse conduction. Although the myelin sheath has traditionally not been considered critical to the pathogenesis of epilepsy, recent reports have demonstrated that CNS myelin sheaths are affected in certain epilepsy patients (Concha et al, 2009;Nilsson et al, 2008;Scanlon et al, 2013;Schoene-Bake et al, 2009), and our previous study confirmed that demyelination of the hippocampus occurs in lithium-pilocarpine-induced epileptic rats (Ye et al, 2013). In addition, epileptic seizures have also been observed in patients with multiple sclerosis, a typical demyelinating disease of the CNS, and in different animal models with myelin diseases (Anderson and Rodriguez, 2011;Bloom et al, 2002;Eguibar and Cortes Mdel, 2010).…”

“…Previous studies of the underlying pathology of epilepsy have confirmed that myelin is affected in certain patients with epilepsy and in epileptic rats (Ye et al, 2013;You et al, 2011), indicating an association between epilepsy and myelin damage.…”

“…Demyelination in the hippocampus has been demonstrated in epileptic rats (Ye et al, 2013;You et al, 2011), and OPCs have the potential to regenerate mature oligodendrocytes under demyelinating conditions. Thus, the myelin sheath, mature oligodendrocytes and OPCs are most likely involved in epileptogenesis.…”

Effects of Intravenous Human Umbilical Cord Blood Mesenchymal Stem Cell Therapy versus Gabapentin in Pentylenetetrazole-Induced Chronic Epilepsy in Rats

“…In agreement with other PTZ kindling [36,37], we have observed an increase in MDA levels and a decrease in the pool of antioxidant enzymes, as is evident from the decreased GSH content and activity of SOD and CATA in brain homogenates. This could be explained since an increased neuronal calcium ion concentration leads to mitochondrial dysfunction, cell damage, and epilepsy [38]. Additionally, reactive oxygen species generation can also support the induction of seizure activity by permitting an excessive increase in glutamate, inducing excitotoxicity [39].…”