Prophylactic treatment with melatonin after status epilepticus: Effects on epileptogenesis, neuronal damage, and behavioral changes in a kainate model of temporal lobe epilepsy

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

Download Full-text

Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽

10.3390/antiox10111702 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1702

Author(s):

Sereen Sandouka ◽

Tawfeeq Shekh-Ahmad

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Antioxidant Capacity ◽

Temporal Lobe ◽

Epileptiform Activity ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

Download Full-text

Close relationship between initial convulsive status epilepticus in early childhood and the later development of mesial temporal lobe epilepsy

Brain and Development ◽

10.1016/s0387-7604(97)82996-8 ◽

1996 ◽

Vol 18 (6) ◽

pp. 472 ◽

Cited By ~ 1

Author(s):

Tateki Fujiwara ◽

Takayasu Tottori ◽

Yuko Kuboto ◽

Kazumi Matsuda ◽

Tadahiro Mihara ◽

...

Keyword(s):

Early Childhood ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Mesial Temporal Lobe Epilepsy ◽

Convulsive Status Epilepticus ◽

Close Relationship ◽

Mesial Temporal Lobe

Download Full-text

Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy

Experimental Neurology ◽

10.1016/j.expneurol.2008.04.040 ◽

2008 ◽

Vol 212 (2) ◽

pp. 468-481 ◽

Cited By ~ 64

Author(s):

Bharathi Hattiangady ◽

Muddanna S. Rao ◽

Ashok K. Shetty

Keyword(s):

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Precursor Cells

Download Full-text

Animal models of status epilepticus and temporal lobe epilepsy: a narrative review

Reviews in the Neurosciences ◽

10.1515/revneuro-2017-0086 ◽

2018 ◽

Vol 29 (7) ◽

pp. 757-770 ◽

Cited By ~ 11

Author(s):

Nikita Nirwan ◽

Preeti Vyas ◽

Divya Vohora

Keyword(s):

Animal Model ◽

Status Epilepticus ◽

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Literature ◽

Clinical Characteristics ◽

Genetic Models ◽

Suitable Animal Model ◽

Effective Models

Abstract Temporal lobe epilepsy (TLE) is the chronic and pharmacoresistant form of epilepsy observed in humans. The current literature is insufficient in explicating the comprehensive mechanisms underlying its pathogenesis and advancement. Consequently, the development of a suitable animal model mimicking the clinical characteristics is required. Further, the relevance of status epilepticus (SE) to animal models is dubious. SE occurs rarely in people; most epilepsy patients never experience it. The present review summarizes the established animal models of SE and TLE, along with a brief discussion of the animal models that have the distinctiveness and carries the possibility to be developed as effective models for TLE. The review not only covers the basic requirements, mechanisms, and methods of induction of each model but also focuses upon their major limitations and possible modifications for their future use. A detailed discussion on chemical, electrical, and hypoxic/ischemic models as well as a brief explanation on the genetic models, most of which are characterized by development of SE followed by neurodegeneration, is presented.

Download Full-text