Showing 7 results for Temporal Lobe Epilepsy
Jafar Mehvari, Zeinab Jaafari, Mohamad Zare, Nasim Tabrizi, Alireza Khosravi Farsani,
Volume 0, Issue 0 (3-2018)
Abstract
Introduction: Sudden unexpected death in epilepsy (SUDEP) is the substantial cause of death in patients with epilepsy (PWE). Electroconductive disorders leading to life-threatening arrhythmia are mostly hypothesized to play a crucial role; however, there is paucity of knowledge in variable among the patients with drug-resistant temporal lobe epilepsy (TLE) compared to the healthy controls.
Methods: The current case-control study has been conducted on 50 drug-resistant TLE patients as the cases and 50 age- and gender-matched healthy subjects selected from their first-degree family members. ECGs were taken when admitted at the hospital (base line), immediately after a seizure incidence and within an hour after the end of the seizure from the cases compared with a random ECG of the controls considering parameters including PR-, RR-, and corrected QT interval (QTc), P wave duration and heart rate (HR) variability.
Results: Shorter corrected QTc interval was notified among the drug-resistant TLE patients compared to the controls (P-value=0.017) in the base line taken ECGs, while the assessments immediately after the seizure revealed significant differences in terms of RR-interval (P-value=0.005) and heart rate (P-value=0.005). Post-ictal ECGs did not differ between the groups (P-value>0.05).
Conclusion: According to the findings of this study, shortened QTc interval at base line ECGs, shortened RR interval and increased HR during the seizure were the ECG elements affected in drug-resistant TLE patients; however, to generalize the outcomes, further studies are required.
Sanaz Eftekhari, Soraya Mehrabi, Fariba Karimzadeh, Mohammad-Taghi Joghataei, Mojtaba Khaksarian, Mahmoud Reza Hadjighassem, Majid Katebi, Mansooreh Soleimani,
Volume 7, Issue 2 (4-2016)
Abstract
Introduction: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS.
Methods: Male Wistar rats were divided into sham (receiving phosphate buffered saline within dorsal hippocampus), pilocarpine (epileptic model of TLE), single injection BDNF (epileptic rats which received single high dose of BDBF within dorsal hippocampus), and multiple injections BDNF (epileptic rats which received BDNF in days 10, 11, 12, and 13 after induction of TLE) groups. Their electrocorticogram was recorded and amplitude, frequency, and duration of spikes were evaluated.
Results: Amplitude and frequency of epileptiform burst discharges were significantly decreased in animals treated with BDNF compared to pilocarpine group.
Conclusion: Our findings suggested that BDNF may modulate the epileptic activity in the animal model of TLE. In addition, it may have therapeutic effect for epilepsy. More studies are
necessary to clarify the exact mechanisms of BDNF effects.
Taghi Naserpour Farivar, Marjan Nassiri-Asl, Pouran Johari, Reza Najafipour, Farid Hajiali,
Volume 7, Issue 4 (10-2016)
Abstract
Introduction: Kainic acid (KA) induces neuropathological changes in specific regions of the mouse hippocampus comparable to changes seen in patients with chronic temporal lobe epilepsy (TLE). According to different studies, the expression of a number of genes are altered in the adult rat hippocampus after status epilepticus (SE) induced by KA. This study aimed to quantitatively evaluate changes in the gene expression of brain neurotransmitter receptors one week after administration of kainic acid in the mouse hippocampus.
Methods: We used 12 BALB/c mice in this study and randomly divided them into 2 groups. To both groups, saline (IP) was administered for 7 days, and on the last day, KA (10 mg/kg, IP) was injected 30 minutes after administration of saline. Subsequently, behavioural changes were observed in mice. Then, in one group (1 day group), 2 hours and in another group (7 days group), 7 days after KA administration, the hippocampus tissue of mice was removed and used for gene expression analyses. Total brain RNA was isolated and reversely transcribed. We performed qPCR using RT2 Profiler TMPCR Array Mouse Neurotransmitter Receptors and Regulators (QIAGEN) containing primers for 84 genes. In this regard, we selected 50 related genes for KA model.
Results: Our results showed significant changes in the gene expression of GABAA subunits receptors, including α1-α3, α5, α6, β2, β3, γ1, ρ, and rho1-2 on day 7 compared with the day 1.
Conclusion: Expression of both inhibitory and excitatory receptors changed after one week. Further studies are needed to find more molecular changes in the gene expression of brain neurotransmitter receptors and regulators over longer periods of time in KA models using RT2 PCR array
Reza Rahmanzadeh, Soraya Mehrabi, Mahmood Barati, Milad Ahmadi, Fereshteh Golab, Sareh Kazmi, Mohammad Taghi Joghataei, Morteza Seifi, Mazaher Gholipourmalekabadi,
Volume 9, Issue 6 (11-2018)
Abstract
Introduction: The resistance of temporal lobe epilepsy to classic drugs is thought to be due to disruption in the excitation/inhibition of this pathway. Two chloride transporters, NKCC1 and KCC2, are expressed differently for the excitatory state of Gamma-Amino Butyric Acid (GABA). The present study explored the effect of bumetanide as a selective NKCC1 inhibitor either alone or in combination with the phenobarbital in the pilocarpine model of epilepsy.
Methods: An animal model of Status Epilepticus (SE) was induced with pilocarpine in Wistar male rats followed by phenobarbital and or bumetanide or saline administration for 45 days after the induction of SE by Intraperitoneal (IP) injection. The rats were monitored, their behavior was recorded, and after 24 hours they were sacrificed to study the expression of NKCC1 and KCC2 using real time PCR.
Results: The data showed that the effects of a combination of bumetanide with phenobarbital on frequency rate and duration of seizure attack were more than those of the phenobarbital alone. In addition, in the bumetanide and combined treatment groups, NKCC1 expression decreased significantly, compared with untreated epileptic animals. A delayed decrement in NKCC1/KCC2 expression ratio after bumetanide application was also observed.
Conclusion: The combination of bumetanide with phenobarbital increases the inhibition of SE and maximizes the potential of GABA signaling pathway, and can be considered as an effective therapeutic strategy in patients with epilepsy.
Sobhan Haghani, Nida Jamali-Raeufy, Motahareh Zeinivand, Soraya Mehrabi, Leila Aryan, Javad Fahanik-Babaei,
Volume 12, Issue 6 (11-2021)
Abstract
Introduction: Although pharmacotherapy is the most common treatment for epilepsy, proper seizure control is not achieved with current medications. This study evaluated the protective effects of the Hepatocyte Growth Factor (HGF) in a rat model of Temporal Lobe Epilepsy (TLE) and explored possible molecular mechanisms.
Methods: A TLE rat model was determined using an intra-hippocampal kainic acid injection (4 μg). Intra-cerebrovascular injection of HGF (6 μg) was performed 30 min before kainic acid injection. Learning and memory impairment were investigated by behavioral tests. The Enzyme-Linked Immunosorbent (ELISA) was used to determine astrogliosis and DNA fragmentation. Changes in neuronal density and mossy fiber sprouting were evaluated by Nissl and Timm staining, respectively.
Results: Behavioral assessments indicated that kainate-treated rats presented spontaneous seizures. Moreover, their alternation percentage scores in the Y-Maze test were lower (P<0.001). Likewise, the passive avoidance test confirmed learning disability in Kainate-treated rats (P<0.001). HGF administration reduced the number of spontaneous seizures, alternation percentage score (P<0.001), and cognitive disturbances (P<0.001). The histopathological results also showed that a protected HGF administration contributed to the reduction of neuronal loss in the CA3 subregion of the hippocampus and inhibited the formation of aberrant Mossy Fiber Sprouting (MFS) (P<0.01). Furthermore, the ELISA data indicated a significant decrease in GFAP (P<0.01) and DNA fragmentation (P<0.05) following HGF administration.
Conclusion: Our findings demonstrated the validity of HGF in protection against the progression of the kainate-induced TLE in rats. This measure improved learning, cognitive disturbances and inhibited apoptosis and astrogliosis.
Farinaz Tabibian, Jafar Mehvari Habibabadi, Mohammad Reza Maracy, Hossein Kahnouji, Mahtab Rahimi, Maryam Rezaei,
Volume 14, Issue 3 (5-2023)
Abstract
Introduction: Temporal lobe epilepsy (TLE) is the most prevalent form of drug-resistant epilepsy with concurrent cognitive impairment. Prevention, earlier diagnosis, and personalized management of cognitive deficits in TLE require more understanding of underlying structural and functional brain Ialterations. No study has evaluated the performance of TLE patients in different cognitive domains based on their structural brain lesions.
Methods: In this study, 69 refractory TLE patients underwent magnetic resonance imaging (MRI) epilepsy protocol and several neuropsychological tests, consisting of the Wechsler adult intelligence scale-revised, Rey-Osterrieth complex figure test, verbal fluency test, digit span test, spatial span test, Wechsler memory scale-III, design fluency test, Rey visual design learning test, auditory-verbal learning test, and trail making test. MRI findings were classified into the following groups: Focal cortical dysplasia, gliosis, atrophy, mesial temporal sclerosis (MTS), tumor, vascular malformation, and other lesions or normal. Results of neuropsychological tests were compared between MRI groups using a generalized linear model with gamma distribution and log link.
Results: Patients with MTS showed better performance in general intellectual functioning, working memory, attentional span, and auditory-verbal learning compared to patients with non-MTS MRI lesions. Atrophy and focal cortical dysplasia had the largest differences from MTS.
Conclusion: Cognitive performance of refractory TLE patients varies concerning structural brain alterations. Further neuroimaging studies of TLE lead to prevention and more accurate management of cognitive decline in clinical settings.
Mandeep Kaur, Tulika Gupta, Mili Gupta, Navneet Singla, Parampreet S Kharbanda, Yogender Singh Bansal, Daisy Sahni, Bishan Das Radotra, Sunil Kumar Gupta,
Volume 14, Issue 5 (9-2023)
Abstract
Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue.
Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15).
Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy.
Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.
