Severe Convulsions Research Articles

The effect of hydroalcoholic extract of Mentha piperita on pentylenetetrazol-induced convulsion in mice

Background: Convulsion is one of the most important disorders of the central nervous system. On account of their lower side effects, the use of medical herbs for treating diseases, including convulsion, is on the rise. Aims and Objectives: The present study aimed at investigating the effect of peppermint extract on pentylenetetrazol (PTZ)-induced convulsion in small white (laboratory) rats. Materials and Methods: This study was conducted on 64 mice. The treatment groups received various (400, 600, and 800 mg/kg) doses of hydroalcoholic peppermint extract. The positive and negative control groups received Diazepam (1 mg/kg) and normal saline (10 ml/kg)30 min before intraperitoneal PTZ injection (85 mg/kg), respectively. Such factors as the onset, length, and severity of convulsion were then studied. To determine the best extract dose, the response times for min 15, 30, 45, and 60 before PTZ injection were studied. Results: Results from the administration doses of the extract revealed that it had a dose-dependent effect in that no convulsion was seen at 800 mg/kg. To investigate the effect of interval between appropriate extract dose injection (800 mg/kg) on PTZ levels, 15-, 30-, 45-, and 60-min intervals were chosen. Results showed that the best result of the 800 mg/kg extract dose was achieved 30 min before PTZ injection where no convulsion was observed. Conclusion: The overall result revealed that peppermint extract had preventive effects on PTZ-induced epileptic attacks in mice where the 800 mg/kg dose brought about the best result, i.e., no convulsion.

A Case of Transient Hypercortisolism Simultaneously Occurring With the Syndrome of Inappropriate Antidiuretic Hormone Secretion Induced by Olanzapine

We herein present a case of a 71-year-old woman who was referred to our hospital with the prolonged disturbance of consciousness after two convulsive seizures the day before admission. She was in long-term hospitalization because of schizophrenia. Blood tests showed severe low-osmolar hyponatremia (Osm: 226 mOsm/kg and Na: 110.3 mEq/L) and hypokalemia (K: 2.67 mEq/L). An endocrine examination revealed that the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which was induced secondary to olanzapine, and transient hypercortisolism had simultaneously occurred. Low- and high-dose overnight dexamethasone suppression tests and the corticotropin-releasing hormone (CRH) test showed similar endocrine responses to those in patients with Cushing’s syndrome. However, no abnormality in the pituitary gland was detected using contrast magnetic resonance imaging (MRI). After admission, elevated adrenocorticotropic hormone (ACTH) and cortisol levels gradually decreased and normalized by the time of discharge. Transient hypercortisolism sometimes occurs in patients with schizophrenia. Hypercortisolism in the present case was considered to be induced by stress such as severe hypo-osmotic hyponatremia and convulsions in addition to the underlying disorder of schizophrenia. Clinicians need to routinely check electrolytes in patients taking olanzapine in order to prevent insidious progression to severe hyponatremia. To the best of our knowledge, this is the first case report in which an endocrine examination and its interpretation were performed for SIADH accompanied by transient hypercortisolism due to the stimulation of ACTH. J Med Cases. 2017;8(8):259-263 doi: https://doi.org/10.14740/jmc2877w

TBCK‐related intellectual disability syndrome: Case study of two patients

There is a significant level of genetic heterogeneity underlying the phenotype of nonspecific hypotonia with severe intellectual disability. Exome sequencing has proven to be a powerful tool for identifying the underlying molecular basis of such nonspecific, abnormal neurological phenotypes. Mutations in the TBCK gene have been reported associated with very poor, if any, psychomotor development, poor speech, and inability to walk independently. We describe the long-term phenotypic evolution of a severe nonspecific neurodevelopmental disorder in two siblings born to an Arab-Moslem family living in northern Israel. Exome sequencing led to identification of a novel homozygous mutation: c.1854delT in the TBCK gene. Abnormal elevated β-HCG was found in the maternal serum during the two pregnancies, a finding that has not been reported before. These individuals present with severe intellectual disability, no speech, hypotonia, convulsions, and lack of any independent daily skills. © 2016 Wiley Periodicals, Inc.

In vitro/in vivo evaluation of gamma-aminobutyric acid-loadedN,N-dimethylacrylamide-based pegylated polymeric nanoparticles for brain delivery to treat epilepsy

Objectives of this study were the delivery of gamma aminobutyric acid (GABA) into the brain by means of developing brain targeted, nanosized, non-toxic and biocompatible polymeric nanoparticles, and investigating their effectiveness in epilepsy. For this purpose, GABA conjugated N,N-dimethylacrylamide-based pegylated nanoparticles were designed and characterised for particle size, zeta potential, pH, morphology, DSC, XRD, FTIR, GABA quantification and in vitro release. Formulations showed smaller particle size, cationic zeta potential characteristic, possible GABA polymeric matrix interaction and prolonged release pattern. Brain responses were examined using epileptic rats. Both formulations prepared were found to increase latency of seizure, decrease ending time of convulsion, duration of severe convulsion and mortality rate significantly compared with GABA solution. When GABA concentration was measured in Stratum corsatum, there was no statistical difference between GABA solution and formulations. All findings suggested enhancement in all phases of seizures indicating efficient delivery of GABA into the brain via formulations.

Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity

Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10h of withdrawal in WSR-1 females and to the initial 24h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity.

Resveratrol fails to provide prophylactic protection in a rat model of organophosphate poisoning.

Background Paraoxonase-1, an organophosphorous-hydrolyzing enzyme, was shown to provide protection against organophosphates poisoning in vivo. In vitro findings suggest that the phytoalexin resveratrol can elevate paraoxonase-1 levels and thus may provide protection against organophosphate poisoning. This study was conducted to evaluate the effect of prolonged resveratrol intake on paraoxonase-1 levels in rats, and its role as a potential prophylactic treatment in organophosphate poisoning. Methods30 adult male albino Sprague–Dawley rats were randomly assigned into three groups: rats receiving no resveratrol (Control group, n = 10), rats treated once daily with oral gavage of ethanol only (Sham group, n = 6), and rats treated once daily with oral gavage of resveratrol (50 mg/kg) (Study group, n = 14). Following 2 weeks of feeding, all rats were exposed to 1.4LD50 paraoxon (450 mg/kg, intramuscular; 0.5 ml/kg) and monitored for severity of clinical signs and mortality. Paraoxonase-1 activity level was recorded in the beginning of the study and 2 weeks later, just before exposure to paraoxon.ResultsWe found a significant decrease in paraoxonase-1 activity levels in all groups compared to baseline levels (p = 0.05), but no significant difference was observed between the study group and the controls (p = 0.7). Following exposure to paraoxon, all animals suffered from severe convulsions and died within minutes.ConclusionsFollowing resveratrol intake in rats, paraoxonase-1 activity levels decreased. We found no beneficial effects in using resveratrol as a prophylactic medical countermeasure.

Lateral hypothalamus orexinergic system modulates the stress effect on pentylenetetrazol induced seizures through corticotropin releasing hormone receptor type 1

Stress is a trigger factor for seizure initiation which activates hypothalamic pituitary adrenal (HPA) axis as well other brain areas. In this respect, corticotropin releasing hormone (CRH) and lateral hypothalamus (LH) orexinergic system are involved in seizure occurrence. In this study, we investigated the role of LH area and orexin expression in (mediation of) stress effect on pentylenetetrazol (PTZ) -induced seizures with hippocampal involvement.Two mild foot shock stresses were applied to intact and adrenalectomized animals; with or without CRHr1 blocking (NBI 27914) in the LH area. Then, changes in orexin production were evaluated by RT-PCR. Intravenous PTZ infusion (25 mg/ml) -induced convulsions were scored upon modified Racine scale. Finally, hippocampal glutamate and GABA were evaluated to study excitability changes.We demonstrated that the duration and severity of convulsions in stress-induced as well as adrenalectomized group were increased. Plasma corticosterone (CRT) level and orexin mRNA expression were built up in the stress and/or seizure groups. Furthermore, glutamate and GABA content was increased and decreased respectively due to stress and seizures. In contrast, rats receiving CRHr1 inhibitor showed reduced severity and duration of seizures, increased GABA, decreased glutamate and corticosterone and also orexin mRNA compared to the inhibitor free rats.Stress and adrenalectomy induced augmenting effect on seizure severity and duration and the subsequent reduction due to CRHr1 blocking with parallel orexin mRNA changes, indicated the likely involvement of CRH1r induced orexin expression of the LH in gating stress effect on convulsions.

Prevalence and Etiology of Seizures in Kashmir

Background: Seizures and epilepsy are common neurological disorders which significantly affect the quality of life. About 10 % of the population experiences a seizure in their lifetime, and are a common source of referrals for neurological consultation. Seizures can vary from the briefest lapses of attention or muscle jerks to severe and prolonged convulsions and vary in frequency, from less than 1 per year to several per day. Owing to scanty information on epidemiology and etiology on seizures in Kashmir, the present study was undertaken to provide update, identify gaps in our present knowledge. Methodology: This was a prospective and observational study undertaken in two phases. In the first phase households in Hazratbal Community Block Srinagar were surveyed for seizure disorder using cluster sampling. Individuals with seizures were clinically evaluated with detailed history and thorough clinical examination as per protocol in the second phase. All patients were subjected to haematological, biochemical and radiological examination. Special investigations like EEG, and CSF analysis were done wherever it was required for patient. Results: The total number of cases included in this study was 47 with male to female ratio of 1:0.88. Majority of the cases were in the age group of 20-39 years followed by 40-59 years. Neuroinfection was the predominant cause of seizures with encephalitis accounting for 12.63%. Other causes included cerebrovascular accidents (25.53%), metabolic (17.02%), miscellaneous (8.51%) and idiopathic (12.76 %).Higher incidence of seizures was observed in the age group of 20-29, followed by 40-49 and 30-39 age groups. Neuroinfection was observed as the leading cause of seizures in the age group of 20- 29 years, followed by age group of 40-49 and 30-39 years. In the age group of 50-59 years metabolic was the common cause of seizures followed by CVA and neuroinfection. Cerebrovascular accidents were found important cause for seizures in all age groups with higher incidence in 40-49 age groups. Conclusion: Prevalence is a measure of the disease burden in the community which has to be considered when planning the health needs. Seizure being a medical emergency, determination of its epidemiology and etiology is a necessary step in its prevention and management. In a sample of 15748 taken randomly out of a population of 150,000, 47 cases of seizure were found. Majority of seizures occurred in the age groups of 20-49 years. Etiological spectrum of seizures was varied and included cerebrovascular accidents, neuroinfection, metabolic, tumour, idiopathic. Neuroinfection and CVA account for significant number of seizures in all age groups.

Tianeptine Co‐administration with Alcohol to Adolescent Rats Modifies the Alcohol Withdrawal Syndrome

Adolescence is a time when many individuals have their first experiences with alcohol and other drugs. It is a time when the brain undergoes important developmental changes that may be altered by drug use. We have shown previously that adolescent Long‐Evans rats consume high levels of an alcohol‐containing liquid diet, achieve correspondingly high blood alcohol concentrations, and develop a subsequent severe alcohol withdrawal syndrome. Using adult rats, tianeptine has been shown by other groups to decrease anxiety‐like behaviors and the onset and severity of convulsions during alcohol withdrawal. The present study was designed to test the effectiveness of tianeptine against the severe alcohol withdrawal syndrome seen with adolescent rats and to test the effects of tianeptine on upregulation of glutamate receptors during adolescent alcohol consumption. Liquid diets were used to administer alcohol and tianeptine, alone and in combination, using a modified chronic intermittent design. After 10 days of co‐administration of tianeptine and alcohol and 6 hours of withdrawal, motor activity showed little or none of the hypoactivity characteristic of alcohol withdrawal. Tianeptine alone had no effect on motor activity under these conditions. However, continued out to 21 days of co‐administration, adolescent rats showed the same high frequency of induced running episodes and convulsions during withdrawal as when alcohol was administered alone. Western blotting was used to determine expression levels for forebrain glutamate receptors, AMPA and NMDA. Both receptors were upregulated during chronic alcohol consumption. During co‐administration with alcohol, tianeptine delayed this upregulation so that at 10 days there was no significant upregulation of AMPA or NMDA whereas significant increases in expression were observed by 21 days. These results indicate that tianeptine may dampen symptoms of adolescent alcohol withdrawal in the short term by delaying the upregulation of excitatory glutamate receptors induced by chronic alcohol. However, tianeptine was ineffective in maintaining this delay and in preventing more severe withdrawal associated with longer term alcohol consumption. Thus, we conclude that tianeptine may be of limited effectiveness against alcohol withdrawal severity in adolescents compared to that suggested previously for adult rats.Support or Funding InformationThis work was supported by the Biology Department and School of Science of Monmouth University.

Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

Gamma-aminobutyric acid loaded halloysite nanotubes and in vitro-in vivo evaluation for brain delivery

Gamma-aminobutyric acid (GABA) is a key neurotransmitter where it usually inhibits impulse transmission. GABA release blockage or postsynaptic reaction were determined to provoke epileptic convulsions. The aim of the present study was the development of brain-targeted, nanosized, nontoxic, biocompatible, highly specific formulations. Incorporation of GABA into halloysite nanotubes (HNT) was performed using different methods. Particle size, zeta potential and pH measurements, morphological, thermal, XRD, FTIR analyses and GABA quantification by validated HPLC method were used for the characterization of the systems prepared. Release pattern of GABA from the nanotubes was determined using a dialysis membrane.Following successful incorporation of GABA into HNTs for brain delivery, nanotube formulation coded HNT–GABA H1 was selected for in vivo studies. Smaller particle size with narrow size distribution, possible HNT–GABA interaction indicated by thermal, XRD and FTIR analyses and prolonged release were the parameters considered in this selection. Moreover, HNT–GABA H1 remained stable for 3-month storage period and showed higher cell viability values than GABA. Rats were used in in vivo studies and potential of anticonvulsant effect of GABA was determined in the pentylenetetrazole model of seizure. HNT–GABA H1 was found to increase latency of seizure, decrease ending time of the convulsion, duration of severe convulsion and mortality rate significantly compared to pure GABA. After administration of HNT–GABA H1, GABA concentration in Stratum corsatum measured by enzyme immune assay showed that it was not significantly higher than GABA administered alone.These findings suggest that GABA loaded HNTs reduces the duration of all phases of convulsion indicating efficient delivery of GABA to all brain areas to interfere with epileptic mechanism.

BPC 157 Counteracts Convulsions after Continuous Haloperidol Overdose Administration in Rats

Aim. We focused on haloperidol induced convulsions in rats and stable gastric pentadecapeptide BPC 157. BPC 157 is an antiulcer peptide tested in clinical trials, for inflammatory bowel disease and multiple sclerosis, showing particular central effects, affecting brain 5-HT release, particularly in substantia nigra, counteracting amphetamine-acute and chronic disturbances as well as gastric lesions and catalepsy induced by various neuroleptics, particularly haloperidol. However, BPC 157 was not tested against continuous application of haloperidol throughout 14 days, in a haloperidol over-dose of the 25 mg/kg/day ip that might induce progressive convulsions. Materials and methods. Rats were daily monitored and filmed 10 minutes before and throughout next 2h after haloperidol administration (25 mg/kg ip) for convulsions presentation (sec), BPC 157 was given (10µg/kg, 10ng/kg i.p.) immediately after haloperidol as described (Jelovac et al., Eur J Pharmacol. 1999;379(1):19-31; Sikiric et al. Curr Pharm Des. 2014;20(7):1126-35.). Results. Convulsions were consistently attenuated since day 1 (means±SD, i.e., for first 30 min 70±10 sec µg vs. 150±10 sec control *P<0.05, at least); day 4, (i.e., for first 30 min 350±30 sec µg vs. 750±40 sec control *P<0.05, at least), day 7, (i.e., for first 30 min 500±30 sec µg vs. 850±40 sec control *P<0.05, at least), day 14, (i.e., for first 30 min 300±30 sec µg vs. 950±40 sec control *P<0.05, at least). Conclusions. Applied after haloperidol, the deleterious course was attenuated after BPC 157 administration, and particularly, severe haloperidol convulsions markedly attenuated. Supported by Grant 108-1083570-3635, Croatia.

Combined Blockade of AMPA and NMDA Receptors Produces Maximal Suppression of the Development of Corasol Kindling in Rats

Chronic enteral administration of the standard antiepileptic drug sodium valproate at a dose of 200 mg/kg suppressed the development of generalized clonic-tonic corasol-kindled convulsions in 100% of rats but prevented kindled clonic convulsions in only 57%. This dose of sodium valproate decreased the mean severity of corasol-kindled convulsions by a factor of 1.7. Chronic enteral administration of IEM-2121, which induces combined blockade of AMPA and NMDA glutamate receptors, and IEM-1676, which blocks AMPA and NMDA receptors, as well as n-cholinoreceptors, given at doses of 10 and 20 mg/kg, respectively, had greater anticonvulsive activity than sodium valproate, as they decreased the mean severity of corasol-kindled convulsions by factors of 2.4–2.7 as compared with controls and prevented kindled clonic convulsions in 87% of rats. Combined blockade of AMPA and NMDA receptors and, possibly, n-cholinoreceptors, produced the greatest suppression of epileptogenesis in relation to both clonic and clonic-tonic corasol-kindled convulsions.

Methylphenidate intoxications in children and adults: exposure circumstances and evidence-based dose threshold for pre-hospital triage

Context. Methylphenidate intoxications mostly have a relatively mild course, although serious complications can occur. Objective. We aimed to characterize methylphenidate exposures and reassess our current dose threshold for hospital referral (2 mg/kg). Methods. In a prospective follow-up study, we analysed 364 consecutive methylphenidate exposures that were reported to the Dutch Poisons Information Center. Patients and/or physicians were surveyed by telephone using standardized questionnaires. Three physicians independently scored the observed severity of the intoxication of each patient as ‘no/mild’ (observation at home) or ‘moderate/severe’ (hospital referral necessary). Results. Unintentional exposures (40%) mostly occurred at home involving the patients’ own medication or those from a family member. Compared to unintentionally exposed patients, intentionally exposed patients were exposed to relatively high methylphenidate doses (3.1 vs 1.6 mg/kg), more often used immediate release methylphenidate formulations (62 vs 34%) and more frequently had concomitant exposures (71 vs 17%). Severe symptoms like convulsions or coma were reported only in patients with concomitant exposures. Following exposure to methylphenidate only (i.e. no concomitant exposures), the most commonly reported symptoms were dry mucosa, headache, agitation, sleepiness and tachycardia. Our results show that the reported methylphenidate dose is predictive of the observed severity of the intoxication and can therefore aid in pre-hospital triage. Conclusion. We increased our current dose threshold for hospital referral from 2 to 3 mg/kg. In addition, we will refer patients at lower doses when clinical symptoms indicate the need for hospital referral. Application of this new dose threshold optimizes triage, thereby reducing unnecessary hospital referral and thus costs, without jeopardising patient safety.

Miller Dieker Syndrome as a Cause of Refractory Seizures

Miller-Dieker syndrome is a genetic deletion syndrome characterized by neuronal migration disorder lissencephaly where the exterior of the brain is abnormally smooth with fewer folds and grooves and characteristic facial dysmorphism. A one year old boy born presented to our emergency with severe respiratory distress and recurrent convulsions. A diagnosis of Miller Diecker syndrome was made consistent with typical clinical features and investigations. The child was managed symptomatically, however the seizures remained refractory and the child succumbed on day three of admission. Diagnosis of rare diseases like this is necessary not only for management but also for predicting recurrence in the family and genetic counselling. Key words: Miller Dieker syndrome; Lissencephaly; Refractory Seizures DOI: http://dx.doi.org/10.3126/jnps.v34i2.9408J Nepal Paediatr Soc 2014;34(2):154-156

Serum ischemia-modified albumin levels in children with epileptic seizures.

The aim of the present study was to determine the level of ischemia-modified albumin (IMA) in children with epileptic seizures (ESs) and its relation with the seizure duration. The study was performed with 88 children as a prospective case-control study. Blood samples for IMA were obtained from 57 patients (mean age [SD], 50.86 [51.15] months) within 3 hours after ES and 31 healthy control subjects (mean age [SD], 53.13 [40.87] months). Ischemia-modified albumin was measured by the albumin cobalt binding test. Although the mean (SD) of serum IMA level of the patients with seizure was 13.66 (13.16) U/mL, the mean (SD) of serum IMA level for the control group was 3.73 (1.93) U/mL. Ischemia-modified albumin levels were significantly higher in patients with seizure, compared with that in the control group (P < 0.01). When patients were grouped in itself according to the duration of ESs, the levels of IMA were detected to be increased in patients as the duration of seizures was lengthened. Increased IMA levels after seizures suggest that IMA assay during seizure may be useful for predicting the diagnosis and severity of convulsion.

Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were exposed to an intermittent ethanol exposure paradigm. Mice were treated with saline or ETX in each withdrawal period, and cortical EEG activity was recorded to determine seizure severity. We observed a progression in seizure activity with each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal-induced spike and wave discharges (SWDs), in terms of absolute number, duration of events, and contribution to EEG power in the 6–10 Hz frequency range. We also evaluated the effects of ETX on handling-induced convulsions. Overall, we observed a decrease in handling-induced convulsion severity in mice treated with ETX. Our findings suggest that ETX may be a useful pharmacological agent for studies of alcohol withdrawal and treatment of resulting seizures.

Effect of Amlodipine and Indomethacin in electrical and picrotoxin induced convulsions in mice

Background and ObjectivesAntiepileptic drugs (AEDs) are the drugs used in the treatment of epilepsy. Many AEDs have been developed, but the ideal AED which can not only prevent but also abolish seizures by correcting the underlying pathophysiology is still not in sight. Calcium channel blockers (CCBs) may form such a group, as the initiation of epileptogenic activity in the neuron is connected with a phenomenon known as “intrinsic burst firing” which is activated by inward calcium current. In this study, Amlodipine, a CCB of the dihydropyridine class was evaluated for its anticonvulsant activity in mice. It was compared with Phenytoin sodium, one of the oldest anti epileptic drugs. Amlodipine was also combined with Indomethacin, a conventional NSAID, to look for any potentiating effect of this prostaglandin-synthesis inhibitor.Materials and MethodsA total of 48 adult Swiss albino mice of either sex weighing 20–30 G were used for this study; 48 were divided into 8 groups, each group containing 6 mice. Group 1–4 MES (50 m Amp for 0.1 secs) induced convulsion method, Group 5–8 evaluated by using the chemo-convulsant, picrotoxin (0.7 mg/kg). Group 1, 5 are controls of MES, Picrotoxin (without treatment). Group 2 &amp;6 administered standard drug phenytoin (0.5mg/100mg i.p), Group 3 &amp; 7: Amlodipine group (8 mg/kg i.p) and Group 4 &amp; 8: Amlodipine (8 mg/kg) and Indomethacin group (20 mg/kg). In MES method Duration of tonic hind limb extension, Clonic convulsions, Recovery period were studied. In Picrotoxin method Latent period before onset of convulsions, severity of convulsions assessed.ResultsIn electrically induced seizures, the 3 parameters compared are duration of tonic hind limb extension, THLE, (P&lt;0.05); duration of clonic seizures (P&gt;0.05); duration of recovery phase (P&lt;0.0001) and in picrotoxin-induced seizures, the 2 parameters are onset of seizures (P&lt;0.05) and severity of seizures (P&lt;0.05).The combination of Amlodipine and Indomethacin showed a superior anticonvulsant effect than the use of Amlodipine alone, in both electrically-induced seizures and picrotoxin-induced seizures in mice.

Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.

Aim:Epilepsy is a chronic neurological disorder with complex pathophysiology. Several evidences suggest a role of oxidative stress and mitochondrial dysfunction in pathophysiology of epilepsy. Hesperidin (Hesp) acts as a powerful anti-oxidant agent against superoxide, singlet oxygen, and hydroxyl radicals. Thus, this study was undertaken to evaluate the possible neuroprotective mechanism of Hesp against pentylenetetrazole (PTZ)-induced convulsions in mice.Materials and Methods:Sixty males Laca mice (20-25 g) were randomly divided into 10 treatment groups (n = 6). Seven days pretreatment of Hesp (100, 200 mg/kg, p.o.) was carried out before PTZ (80 mg/kg, intraperitoneal [i.p.]) challenge, whereas diazepam (DZP) (0.2, 0.5 mg/kg) and gabapentin (Gbp) (10, 20 mg/kg) were administered i.p. 30 min before PTZ administration, that is, on 7th day. Following PTZ challenge, severity of convulsions (onset of jerks, myoclonic seizures, extensor phase and death), brain anti-oxidant enzyme levels and mitochondrial complex enzymes activities were estimated.Results:Single i.p. PTZ (80 mg/kg) challenge demonstrated severe convulsions, oxidative damage (raised lipid peroxidation [LPO], nitrite concentration as well as depleted reduced glutathione, superoxide dismutase and catalase levels), and depletion of mitochondrial enzyme Complex (I, II, IV) activities. Hesp (200 mg/kg), DZP (0.5 mg/kg) and Gbp (20 mg/kg) pretreatments attenuated PTZ induced behavioral, biochemical and mitochondrial alterations. However, administration of Hesp (100 mg/kg) in combination with DZP (0.2 mg/kg) or Gbp (10 mg/kg) potentiated their neuroprotective effect, which was significant as compared to their effects in PTZ treated animals.Conclusion:Hesp possesses potent anticonvulsant activity which might be mediated through modulation of gamma-amino butyric acid/benzodiazepine receptor action.

Toxicity Effects of Hair Dye Application on Liver Function in Experimental Animals

Objective: This study was conducted to assess the hair dye toxicity by using hair dye among experimental rats in order to verify the biochemical and haematological abnormalities and liver dysfunction. Methods: Albino Wistar Rats were obtained from the Faculty of Pharmacy, University of Khartoum– Sudan. The rats were divided into two batches on the basis of using the commercial hair dye as oral or subcutaneous administration respectively; each batch has four groups (control and three test groups) each comprising six rats. Batch-1 (group-2, 3, and 4 orally administered with 10, 20, and 30mg/kg body weight of the commercial hair dye, respectively); and Batch-2 (group-2, 3, and 4 subcutaneously administered with 10, 20, and 30 mg/kg body weight of the commercial hair dye, respectively). Results: The clinical features were shown in all rats batches, administered orally or subcutaneously with the commercial hair dye. These clinical features rates from slight weakness in group 2 to head, neck, and pharyngeal oedema in group-3 up to severe weakness in hinds and fore limbs with election of hair, tremors, shivering of the whole body and respiratory distress, severe convulsions, and respiratory difficulty prior to death in group-4. The Biochemical parameters showed significant (P<0.05) increase in the activities of the liver enzymes concomitant with the increase of the commercial hair dye dosage in the two batches, and decrease in the total plasma protein levels, albumin, and cholesterol with the increase of commercial hair dye dosage in the two batches. Hematological parameters showed a significant (p value <0.05) decrease in complete blood count (associated with significant decreases in neutrophils and significant increases of lymphocytes) concomitant with the increasing of commercial hair dye concentration. Conclusion: The study highlighted the major toxicity of commercial hair dye and its association with liver dysfunction.