Basic and Clinical Neuroscience
Volume:11 Issue: 6, Nov-Dec 2020

Absence epilepsy is a brief non-convulsive seizure associated with sudden abruptness in consciousness. Because of the unpredictable occurrence of absence seizures and the ethical issues of human investigation on the pathogenesis and drug assessment, researchers tend to study animal models. This paper aims to review the advantages and disadvantages of several animal models of nonconvulsive induced seizure.

The articles that were published since 1990 were assessed. The publications that used genetic animals were analyzed, too. Besides, we reviewed possible application methods of each model, clinical types of seizures induced, purposed mechanism of epileptogenesis, their validity, and relevance to the absence epileptic patients. 

The number of studies that used genetic models of absence epilepsy from years of 2000 was noticeably more than pharmacological models. Genetic animal models have a close correlation of electroencephalogram features and epileptic behaviors to the human condition.

The validity of genetic models of absence epilepsy would motivate the researchers to focus on genetic modes in their studies. As there are some differences in the pathophysiology of absence epilepsy between animal models and humans, the development of new animal models is necessary to understand better the epileptogenic process and, or discover novel therapies for this disorder.

Broad neural circuits originate from the hypothalamic arcuate nucleus and project to many parts of the brain which are related to pain perception. Insulin receptors are found in the arcuate nucleus. Since nociception may be affected in type 1 diabetes, the present study aimed to investigate the intra-arcuate nucleus insulin role in pain perception in streptozotocin (STZ)-induced diabetic and healthy rats.

Regular insulin was microinjected within the arcuate nucleus and the pain tolerance was measured using the hot plate and the tail-flick apparatus in diabetic rats.

The results showed that the arcuate nucleus suppression with lidocaine could increase thermal nociception in non-diabetic animals. Also, insulin within the arcuate nucleus decreased the acute thermal pain perception in these animals. STZ-induced diabetes produced hypoalgesia which the latency of these tests, progressively increased over time after induction of diabetes. Also, in the same animal group, intra-arcuate injection of insulin reduced the latency of nociception.

Intra-arcuate insulin has paradoxical and controversial effects in healthy and diabetic rats’ nociception. These effects seem to be due to the insulin effect on releasing pro-opiomelanocortin and its deriv

Functional magnetic resonance imaging (fMRI) methods have been used to study sensorimotor processing in the spinal cord. However, these techniques confront unwanted noises to the measured signal from the physiological fluctuations. In the spinal cord imaging, most of the challenges are consequences of cardiac and respiratory movement artifacts that are considered as significant sources of noise, especially in the thoracolumbar region. In this study, we investigated the effect of each source of physiological noise and their contribution to the outcome of the analysis of the blood-oxygen-level-dependent signal in the human thoracolumbar spinal cord.

Fifteen young healthy male volunteers participated in the study, and pain stimuli were delivered on the L5 dermatome between the two malleoli. Respiratory and cardiac signals were recorded during the imaging session, and the generated respiration and cardiac regressors were included in the general linear model for quantification of the effect of each of them on the task-analysis results.  The sum of active voxels of the clusters was calculated in the spinal cord in three correction states (respiration correction only, cardiac correction only, and respiration and cardiac noise corrections) and analyzed with analysis of variance statistical test and receiver operating characteristic curve.

The results illustrated that cardiac noise correction had an effective role in increasing the active voxels (Mean±SD= 23.46±9.46) compared to other noise correction methods. Cardiac effects were higher than other physiological noise sources

In summary, our results indicate great respiration effects on the lumbar and thoracolumbar spinal cord fMRI, and its contribution to the heartbeat effect can be a significant variable in the individual fMRI data analysis. Displacement of the spinal cord and the effects of this noise in the thoracolumbar and lumbar spinal cord fMRI results are significant and cannot be ignored.

Purpose of the study:

 Pelvic floor muscles dysfunction is one of the most important etiologies of coccydynia, therefore, manual therapies have been proposed as the first line of treatment. The purpose of this study was to investigate the effect of biofeedback as a new approach in the treatment of coccydynia.

Thirty women were randomized into two groups. Both groups were injected with corticosteroid. One group received pelvic floor muscle exercises plus biofeedback while the other only performed exercises. Patient’s pain was measured using Visual Analogue Scale (VAS) in the first visit and after 1, 2 and 6 months of follow-up as well as Dallas pain and SF-36 quality of life questionnaires before and 2 months after the treatment.

Pain had improved significantly after 1, 2 and 6 months in both groups compared to the baseline. However, the amount of change was not different between the groups at any time interval. The results were the same for Dallas pain scale and SF-36 quality of life questionnaire.

Adding biofeedback to pelvic floor muscle exercises did not lead to any further improvement in management of chronic coccydynia. Further studies with larger sample sizes may show the effect of biofeedback more clearly.

Oxidative stress has recently emerged as a possible mechanism in the pathogenesis of epilepsy. Coenzyme Q10 (CoQ10) is a strong endogenous antioxidant that protects cells from lipid oxidation and Reactive Oxygen Species (ROS) production; however, the impact of CoQ10 on seizure characteristics in epileptic patients is unclear.

The current study enrolled patients with Epileptic Seizure (ES) to evaluate their serum concentration of CoQ10 and to investigate whether a relationship exists between CoQ10 levels with the duration, frequency, and type of seizure. 

A total of 39 patients with epileptic seizures and 35 healthy controls were included in the study. The levels of CoQ10 in ES patients were significantly lower in comparison with healthy controls (11.99±5.93 vs (ng/ml). 16.48±4.20 (ng/ml) P<0.001). We also found that the duration of epilepsy and seizure frequency was negatively correlated with serum CoQ10 levels.

These findings indicate that CoQ10 deficiency might substantially contribute to the clinical signs of epileptic patients.

Ventral Tegmental Area (VTA) dopamine neurons play an important role in reward mechanisms of food intake, and VTA dopamine receptors exist on the terminal of glutamatergic and GABAergic neurons and regulate Gamma-Aminobutyric Acid (GABA) and glutamate release. To our knowledge, no evidence indicates any role for VTA D1 dopamine receptors in regular chow intake.

In this paper, different dose of SKF38393, a D1 receptor agonist, was microinjected in VTA of 18-h food deprived-conscious rats and food intake was measured.

Our results revealed that VTAmicroinjected SKF383993 increased regular chow intake in a dose-dependent manner. The SKF3833 stimulatory effect persisted over 2 h post-injection. The results showed that the SKF38393, at doses less than 5 μg, did not affect locomotor activities.

VTA D1-like and/or serotonergic receptors may be involved in regulatory pathways. the current study suggests that VTA D1-like and/or serotonergic receptors not only affects food reward but is also involved in regulatory mechanisms of regular feeding.

Diabetic encephalopathy is described as any cognitive and memory impairments associated with hippocampal degenerative changes, including the neurodegenerative process and decreased number of living cells. Mitochondrial diabetes (MD) appears following activation of mutant mitochondrial DNA and is a combination of diabetes and cognitive deficit. In this research, we showed the correlation of diabetic encephalopathy, dysfunctional mitochondria, and changes in the expression of axonal transport proteins (KIF5b, Dynein).

Twenty-four male Wistar rats were divided into three groups: (n=8 in each group):1. Control + saline; 2. Diabetic, and 3. Diabetic + insulin. Before starting the experiments, the animals with blood sugar lower than 150 mg/dL entered the study. Diabetes induction was carried out by Intraperitoneal (IP) Streptozotocin (STZ) administration. Fasting Blood Sugar (FBS) and body weight was checked after the first week and at the end of the eighth week. Then, behavioral studies (elevated plus maze, Y-maze, and passive avoidance learning) were performed. After behavioral studies, blood samples were taken to measure serum insulin level and HgbA1c. Next, fresh hippocampal tissue was collected. Gene expression of motor proteins was assessed by real-time PCR and mitochondrial membrane potential by rhodamine123.

Our results showed the impairment of HgbA1c, serum insulin, FBS, and weight in the diabetic group (P<0.05). Behavioral tests revealed different degrees of impairment in diabetic rats (P<0.05). KIF5b mRNA expression increased in the hippocampus (P<0.05) with no change in dynein gene expression. These changes were associated with abnormal mitochondrial membrane potential (P<0.05).

KIF5b mRNA up-regulation in hippocampal neurons of STZ-diabetic rats is a factor that can be involved in abnormal axonal transport and decreased MMP, leading to impairment of mitochondrial function. These manifestations showed mitochondrial dysfunction in diabetes and resulted in abnormal behavioral tests and diabetic encephalopathy.

Hepcidin is the main modulator of systemic iron metabolism, and its role in the brain has been clarified recently. Studies have shown that hepcidin plays an important role in neuronal iron load and inflammation. This issue is of significance because neuronal iron load and inflammation are pathophysiological processes that are highly linked to neurodegeneration. Moreover, the activity of hepcidin has recently been manipulated to recover the neuronal impairment caused by brain inflammation in animal models.

Streptozotocin (STZ) was used to induce type 1 diabetes. Male Wistar rats (n = 40) with a weight range of 200–250 g were divided into control, diabetic, diabetic + insulin, and diabetic + dalteparin groups. Dalteparin (100 mg/kg IP) and insulin (100 mg/kg SC) were administered for 8 weeks. At the end of the experiment, Y-maze and passive avoidance tasks were carried out. The animals were perfused randomly and their hippocampal tissue was isolated for the analysis of markers such as lipid peroxidation like Malondialdehyde (MDA), hepcidin expression, iron, and ferritin. Blood samples were taken for the measurement of serum inflammatory cytokine Interleukin (IL)-6.

The findings indicated that treatment with dalteparin reduced IL-6, MDA, ferritin, and hepcidin expression in diabetic rats compared to treatment with insulin (P<0.05). Moreover, treatment with dalteparin did not decrease the iron level or prevented its decline.

Treatment with dalteparin improved the cognitive dysfunctions and symptoms of Alzheimer disease in STZ-induced diabetic rats by appropriately modulating and reducing oxidative stress and neuroinflammation. This may enhance the existing knowledge of therapeutics to reduce cognitive impairment in diabetes and is suggested to be a potential therapeutic agent in diabetes.

To evaluate Low-Molecular-Weight (LMW) DNA as a possible prognostic biomarker in acute ischemic and hemorrhagic stroke.

LMW DNA samples were isolated from plasma and cerebrospinal fluid by phenol deproteinization, analyzed by gradient polyacrylamide electrophoresis and quantified by spectrophotometry.

Two common types of stroke, i.e. ischemic and hemorrhagic, differ by the temporal dynamics of cell-free DNA (cfDNA) accumulation. In hemorrhagic stroke, an initial increase in LMW DNA levels, most likely reflects an extent of the tissue damage, while in ischemic patients, the LMW DNA levels increase in parallel with the damage caused by hypoxia and subsequent compensatory reperfusion.

These time-course data specify optimal assessment windows with maximum differentiating power for stroke outcomes: 24-48 hours post-event for ischemic stroke, and as close as possible to the moment of hospital admission for hemorrhagic stroke. These data also indicate the role of apoptosis in the formation of ischemic focus.

MicroRNAs (miRNAs or miRs) are non-coding RNAs. Studies have shown that miRNAs are expressed aberrantly in stroke. The miR1 enhances ischemic damage, and a previous study has demonstrated that reduction of miR1 level has a neuroprotective effect on the Middle Cerebral Artery Occlusion (MCAO). Since apoptosis is one of the important processes in neural protection, the possible effect of miR1 on this pathway has been tested in this study. Post-ischemic administration of miR1 antagomir reduces infarct volume via bcl-w and bad expression. 

Rats were divided into four experimental groups: sham, control, positive control, and antagomir treatment group. One hour after MCAO surgery, the rats were received intravenously (Tail vein) 0.1 mL Normal Saline (NS), 0.1 mL rapamycin, and 300 pmol/g miR1 antagomir (soluble in 0.1 mL normal saline) in control, positive control, and treatment group, respectively. Twenty-four hours after reperfusion infarct volume was measured. The expression of miR1, bcl-w, and bad were analyzed using real-time PCR in sham, control, and treated groups.

 Our results indicate that administration of miR1 antagomir reduces infarct volume significantly, it also decreases miR1 and bad expression while increases bcl-w expression. 

Understanding the precise neuroprotective mechanism of miR1 antagomir can make it a proper treatment and an innovative approach for stroke therapy.

This study aimed to evaluate the effects of bilateral carotid artery occlusion on cochlear oxidative stress and hearing status in rats.

The rats were divided into two sets. The first set was used for electrophysiological recording (click and 4 kHz tone burst auditory brainstem responses and electrocochleography) on the day before surgery and then on the first, fourth, and seventh days after surgery. Animals of the second set were used for biochemical analysis. The cochlea of animals in the second set was collected on the first, fourth, and seventh days after carotids occlusion for biochemical analysis. For the control groups, no carotids occlusion was done. For ischemia induction, both common carotid arteries were occluded for 20 minutes.

 Electrophysiological analysis showed that burst auditory brainstem thresholds significantly elevated after common carotid arteries occlusion on the first, fourth, and seventh days after surgery with abnormal electrocochleography results at 75%, 70%, and 85% on the first, fourth, and seventh days after surgery, respectively. The electrophysiological finding confirmed by biochemical results that showed malondialdehyde and nitric oxide levels increased and superoxide dismutase and catalase activities decreased after occlusion in cochlea tissue.

This study showed that bilateral common carotid artery occlusion increases cochlear oxidative stress and induces hearing loss in rats.

The interaction between antiepileptic drugs and brain electrical stimulation is a potential therapy to control seizures in patients with pharmacoresistance to drugs. So, the present study aimed to design to determine the effect of a subeffective dose of sodium valproate combined with low-frequency electrical stimulation during kindling.

One tripolar electrode was implanted stereotactically in the CA1 hippocampus of male Wistar rats. One week after surgery, the rats were kindled by electrical stimulation of hippocampus in a rapid manner (12 stimulations/day) for 6 days with sodium valproate alone or combined with low-frequency electrical stimulation (four packages contained 200 monophasic square wave pulses of 0.1-ms duration at 1 Hz, immediately after kindling stimulations). The duration of afterdischarge, maximum latency to stages 4 and 5, and the maximum duration of these stages were recorded by electromadule during kindling.

Application of sodium valproate with low-frequency electrical stimulation caused a reduction in cumulative afterdischarge duration. The maximum latency to the onset of stage 5 seizure increased after sodium valproate application alone, without having a significant effect on the fourth stage. Our findings showed reductions in the seizures duration and increasing in the latency times of both stages after the application of sodium valproate with low-frequency electrical stimulation.

It seems that usage of sodium valproate with low-frequency electrical stimulation during kindling was more effective to suppress the epileptic activity than its administration alone and may have a critical role on the antiepileptic effects of sodium valproate.

This study examined the effect of proficiency level on the second Language (L2) syntactic and semantic processing by addressing the role of procedural and declarative memory systems in light of the Declarative/Procedural (DP) model. The primary purpose was to determine to what extent proficiency accounts for native-like language processing in L2 in adult bilinguals who learned English (L2) after the age of 15 under explicit instruction.

Using a mixed-method design and an oddball violation paradigm, we examined the functional neural correlates of syntactic and semantic processing in two groups of Persian-English bilinguals (L1=Persian, L2=English; N=10 high-proficient, N=10 pre-intermediate levels; Gender= Female; mean age=25.50 years, SD = 5.09 years, age range = 19-35 years of age) across 6 different conditions. They included a visual stimulus task of 240 English sentences with three different experimental conditions (violated regular past forms or phrase structure rules or final-word semantic violation) and three control conditions (sets of correct sentences for each experimental condition). Both groups started learning English late (age of onset=15+) and under an explicit learning context. To evaluate the effect of L2 proficiency,  Event-related potentials (ERPs) to target words in each condition were elicited across the N400 time window (300-500 ms) and the P600 time window (500-700 ms).

Results showed different cortical responses in the two groups. Upon processing the violated forms, high-proficient subjects showed more native-like patterns of scalp activity in both lexical-semantic and syntactic processing. In contrast, less proficient learners have shown delayed onsets and or peaks of components, reduced amplitudes, or absent components in some regions. For instance, the difference in N400 amplitude for the incorrect regular past conditions was observed only in the pre-intermediate (PI) subjects in the O1 channel. This finding is compatible with the DP Model in that at lower levels of L2 proficiency, the participants show N400s or N400-like posterior negativities instead of Anterior Negativities (ANs). This finding shows the initial reliance on the declarative memory system for syntactic processing at lower levels of L2. 

Our findings suggest that attained proficiency was a more determinant factor in the L1-like cortical representation of L2 than the age of acquisition and or the type of instruction/context. Several brain areas, similar to those observed for L1, were activated during L2 syntactic processing in high-proficient subjects addressing their reliance on the procedural memory system for syntactic processing to gain more proficiency. For instance, our results showed a significant difference in N400 amplitude for the incorrect regular past conditions in O1 for the PI subjects, which shows the initial reliance on the declarative memory system for syntactic processing at lower levels of L2.

Myxoma may cause systemic embolization and frequently presents as ischemic stroke. 

There have been debates about whether it is safe to use recombinant tissue plasminogen activator (rt-PA) in patients with cardiac myxoma who referred with ischemic stroke to the hospitalchr('39')s emergency. 

The patient was a young case of atrial myxoma with initial presentation of acute cerebral infarction symptoms who was treated with intravenous rt-PA with no complications.

The case provides an evidence of the efficacy and safety of intravenous rt-PA in cases of cardiac myxoma. However, we cannot always expect thrombolytic therapy to be effective, especially in tumor emboli.